Cardia Tumor Pathology

Current Clinical Pathology
Antonio Giordano, MD, PhD

SERIES EDITOR
Director, Sbarro Institute for Cancer Research
and Molecular Medicine and Center for Biotechnology
Temple University
Philadelphia, PA, USA
For further volumes:

http://www.springer.com/series/7632
wwwwwwwwwwww
Cristina Basso • Marialuisa Valente
Gaetano Thiene
Editors
Cardiac Tumor
Pathology
Editors
Cristina Basso Marialuisa Valente
Pathological Anatomy Pathological Anatomy
Department of Cardiac Department of Cardiac
Thoracic and Vascular Sciences Thoracic and Vascular Sciences
Padova, Italy Padova, Italy
Gaetano Thiene
Pathological Anatomy
Department of Cardiac
Thoracic and Vascular Sciences
Padova, Italy
ISBN 978-1-62703-142-4 ISBN 978-1-62703-143-1 (eBook)

DOI 10.1007/978-1-62703-143-1
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2012950036
© Springer Science+Business Media New York 2013

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or
part of the material is concerned, specifically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way,
and transmission or information storage and retrieval, electronic adaptation, computer software,
or by similar or dissimilar methodology now known or hereafter developed. Exempted from this
legal reservation are brief excerpts in connection with reviews or scholarly analysis or material
supplied specifically for the purpose of being entered and executed on a computer system, for
exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is
permitted only under the provisions of the Copyright Law of the Publisher’s location, in its
current version, and permission for use must always be obtained from Springer. Permissions for
use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable
to prosecution under the respective Copyright Law.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of
publication, neither the authors nor the editors nor the publisher can accept any legal responsibility
for any errors or omissions that may be made. The publisher makes no warranty, express or
implied, with respect to the material contained herein.
Printed on acid-free paper
Humana Press is a brand of Springer

Springer is part of Springer Science+Business Media (www.springer.com)
To the memory of Ivan Mahaim, a visionary
in the diagnosis and treatment of cardiac
tumors
wwwwwwwwwwww
Preface
Cardiac tumors were once considered a nosographic entity of scanty interest

because of their rarity, the intrinsic diagnostic difficulty and the therapeutic
impossibility. They were mostly fatal or incidental findings at postmortem.
Nowadays they have become a topical subject because of the great advances
in clinical imaging (echocardiography, magnetic resonance, and computed
tomography) and surgical treatment and are a spectacular example of innova-
tion in technology for in vivo diagnosis and therapy.
The present monograph goes over these advances with clinicopathologic
correlations. About 90% of primary cardiac tumors are benign and the sim-
ple surgical removal is curative forever. Another proof as cardio-pulmonary
bypass with cardiac arrest and open-heart surgery was a revolutionary step
forward in cardiovascular medicine.
The book covers history, epidemiology, demographics, clinical diagnosis,
imaging, surgery, pathology, and basic sciences aspects of both benign and
malignant cardiac neoplasms, either primary or secondary. Chemotherapy
and radiotherapy of malignant neoplasms is as well as cardiotoxicity are
also addressed.
The book is directed to all the researchers and physicians involved in the
field of cardiac oncology, from cardiologists to cardiac surgeons, from radi-
ologists to pathologists. In this regard, it must be said that cardiac surgery
opened the era of surgical pathology also in the field of cardiac diseases.
As far as cardiac tumors, although tissue characterization with imaging is
tempting, histology and immunohistochemistry remain irreplaceable life-
saving steps for diagnosis. The presence of an expert cardiovascular patholo-
gist is fundamental in the clinical team dealing with cardiac tumors. This is
the reason why pathologists should be interested in reading and consulting
the book which however, at difference from previous authoritative books and
atlas, include robust clinical and imaging information, with several chapters
written by clinicians and surgeons, which represent its peculiarity.
Padua, Italy Cristina Basso M.D., Ph.D.

Marialuisa Valente M.D.
Gaetano Thiene M.D.
vii
wwwwwwwwwwww
Acknowledgments
The Editors are supported in their research by the Registry of Cardio-

cerebro-vascular Pathology, Veneto Region, Venice, Italy.
They also acknowledge Mrs. Chiara Carturan and Mr. Marco Pizzigolotto
for their editorial and graphical assistance in preparing this book.
ix
wwwwwwwwwwww
Contents
1 Cardiac Tumors: From Autoptic Observations

to Surgical Pathology in the Era of Advanced
Cardiac Imaging............................................................................ 1
Gaetano Thiene, Marialuisa Valente, and Cristina Basso
2 Cardiac Tumors: Classification and Epidemiology ................... 23
Gaetano Thiene, Cristina Basso, Stefania Rizzo,
Gino Gerosa, Giovanni Stellin, and Marialuisa Valente
3 Cardiac Myxoma........................................................................... 31
Giovanni Bartoloni and Angela Pucci
4 Other Benign Cardiac Tumors .................................................... 45
Cristina Basso, Tomaso Bottio, Gaetano Thiene,
Marialuisa Valente, and Gino Gerosa
5 Primary Cardiac Tumors in the Pediatric Age .......................... 59
Massimo A. Padalino, Cristina Basso, Ornella Milanesi,
Gaetano Thiene, and Giovanni Stellin
6 Primary Malignant Tumors of the Heart ................................... 73
Marialuisa Valente, Stefania Rizzo, Ornella Leone,
and Cristina Basso
7 Echocardiographic Approach to the Diagnosis
of Cardiac Tumors ........................................................................ 91
Paolo Voci and Francesco Pizzuto
8 Echocardiography of Cardiac Masses:
From Two- to Three-Dimensional Imaging ................................ 101
Luigi P. Badano, Denisa Muraru, and Sabino Iliceto
9 New Cardiac Imaging Techniques:
Magnetic Resonance and Computed Tomography .................... 115
Massimo Lombardi
10 Surgical Management of Cardiac Neoplasms ............................ 131
Francesco Santini, Mariassunta Telesca, Giuseppe Faggian,
and Alessandro Mazzucco
xi
xii Contents
11 Cardiac Metastases ....................................................................... 151

Furio Silvestri, Gianfranco Sinagra, and Rossana Bussani
12 Systemic Therapy, Radiotherapy, and Cardiotoxicity............... 165
Chiara Lestuzzi, Gianmaria Miolo, and Antonino De Paoli
13 Novelties in Immunohistochemical
and Molecular Study of Cardiac Tumors ................................... 183
Augusto Orlandi and Luigi Giusto Spagnoli
Index ....................................................................................................... 195

Contributors
Luigi P. Badano, M.D. Cardiology, Department of Cardiac, Thoracic and

Vascular Sciences, Azienda Ospedaliera-University of Padua Medical School,
Padua, Italy
Giovanni Bartoloni, M.D. Histopathology Department, “GB Ingrassia”
Catania University, Garibaldi-Catania, Catania, Italy
Cristina Basso, M.D., Ph.D. Pathological Anatomy, Department of Cardiac,
Thoracic and Vascular Sciences, Azienda Ospedaliera-University
of Padua Medical School, Padua, Italy
Tomaso Bottio, M.D., Ph.D. Cardiac Surgery, Department of Cardiac,
Thoracic and Vascular Sciences, Azienda Ospedaliera-University of Padua
Medical School, Padua, Italy
Rossana Bussani, M.D. Department of Pathologic Anatomy, University
of Trieste Medical School, Trieste, Italy
Antonino De Paoli, M.D. Department of Radiation Oncology, Centro di
Riferimento Oncologico (CRO), National Cancer Institute, Aviano (PN), Italy
Giuseppe Faggian, M.D. Cardiac Surgery, University of Verona Medical
School, Verona, Italy
Gino Gerosa, M.D. Cardiac Surgery, Department of Cardiac, Thoracic
and Vascular Sciences, Azienda Ospedaliera-University of Padua Medical
School, Padua, Italy
Sabino Iliceto, M.D. Cardiology, Department of Cardiac, Thoracic and
Vascular Sciences, University of Padua Medical School, Padua, Italy
Ornella Leone, M.D. Department of Pathology, S. Orsola-Malpighi
Hospital, Bologna, Italy
Chiara Lestuzzi, M.D. Department of Cardiology, Centro di Riferimento
Oncologico (CRO), National Cancer Institute, Aviano (PN), Italy
Massimo Lombardi, M.D. Cardiovascular MR Unit, Fondazione C.N.R./
Regione Toscana “G. Monasterio”, Pisa, Italy
Alessandro Mazzucco, M.D. Cardiac Surgery, University of Verona
Medical School, Verona, Italy
xiii
xiv Contributors
Ornella Milanesi, M.D. Pediatric Cardiology, Department of Pediatrics,

Azienda Ospedaliera-University of Padua Medical School, Padua, Italy
Gianmaria Miolo, M.D. Department of Medical Oncology, Centro di
Riferimento Oncologico (CRO), National Cancer Institute, Aviano (PN), Italy
Denisa Muraru, M.D. Cardiology, Department of Cardiac, Thoracic and
Vascular Sciences, University of Padua Medical School, Padua, Italy
Augusto Orlandi, M.D. Department of Biomedicine and Prevention,
Institute of Anatomic Pathology, Tor Vergata University, Rome, Italy
Massimo A. Padalino, M.D., Ph.D. Pediatric Cardiac Surgery, Department
of Cardiac, Thoracic and Vascular Surgery, Azienda Ospedaliera-University
of Padua Medical School, Padua, Italy
Francesco Pizzuto, M.D. Department of Internal Medicine, Section of
Cardiology, Tor Vergata University, Rome, Italy
Angela Pucci, M.D. Histopathology Department, Azienda Ospedaliera-Pisa
University Hospital, Pisa, Italy
Stefania Rizzo, M.D. Pathological Anatomy, Department of Cardiac,
Francesco Santini, M.D. Cardiac Surgery, University of Verona Medical
Furio Silvestri, M.D. Department of Pathologic Anatomy, University of
Trieste Medical School, Cattinara Hospital, Trieste, Italy
Gianfranco Sinagra, M.D. Cardiovascular Department, University of
Trieste Medical School, Cattinara Hospital, Trieste, Italy
Luigi Giusto Spagnoli, M.D. Department of Biomedicine and Prevention,
Institute of Anatomic Pathology, Tor Vergata University, Rome, Italy
Giovanni Stellin, M.D. Pediatric Cardiac Surgery, Department of Cardiac,
Mariassunta Telesca, M.D. Cardiac Surgery, University of Verona Medical
Gaetano Thiene, M.D. Pathological Anatomy, Department of Cardiac,
Marialuisa Valente, M.D. Pathological Anatomy, Department of Cardiac,
Paolo Voci, M.D. Department of Internal Medicine, Section of Cardiology,
Tor Vergata University, Rome, Italy
Cardiac Tumors: From Autoptic
Observations to Surgical 1
Pathology in the Era of
Advanced Cardiac Imaging
Gaetano Thiene, Marialuisa Valente,

and Cristina Basso
In the popular mind, the term “tumor” recalls the in Rome at that time, he discovered a left ven-
concept of “cancer,” i.e., a highly aggressive bio- tricular mass described as follows in Latin “In
logical process eventually leading to body con- Cardinali Gambara Brixiano tumorem praedu-
sumption due to malignant infiltration and rum, et ad ovi magnitudinem in sinistro cordis
metastasis. ventricolo Romae vidi, ubi illum in affinium gra-
This is not the case at the heart level, since tiam dissecarem” (“in Rome I saw a solid tumour,
malignant primary cardiac tumors are rare (about large like an egg, in the left ventricle of Cardinal
10% of all primary cardiac tumors). Malignancy Gambaro of whom I was committed by the Pope
is hemodynamic rather than biological, due to to make autopsy”) (Fig. 1.1). Most likely it was a
obstruction of the blood circulation because of post-infarction endocavitary apical mural throm-
intracavitary growth and embolism of neoplastic bus rather than a true neoplasm.
fragments with potentially devasting ischemic In the famous article entitled Tumors of the
damage to several organs. heart: review of the subject and report of one
Before the advent of cardiac imaging and of hundred and fifty cases, dated 1951 [2], Richard
open heart surgery, cardiac neoplasms were not Prichard wrote “…the most common cardiac
diagnosed in vivo and were mostly fatal due to tumour (cardiac myxoma) has never been diag-
complications along their natural history and, as nosed antemortem…”. Noteworthy, in the Mayo
such, diagnosed by the pathologist only at Clinic experience published in 1980, 23% of sur-
postmortem. gically resected cardiac myxomas were referred
Noteworthy, the first description of cardiac to surgery on the basis of auscultatory signs and
tumors was made by Matteo Realdo Colombo in symptoms suggestive of rheumatic mitral valve
1559 in his book De Re Anatomica [1]. While stenosis [3].
performing the autopsy of the body of Cardinal The first book on cardiac tumors was pub-
Gambaro from Brescia, since he was the archiater lished by Ivan Mahaim in 1945 (Fig. 1.2) with the
title Les tumeurs et les polypes du coeur: etude
anatomo-clinique [4].
G. Thiene, M.D. (*) • M. Valente, M.D. At the Institute of Pathological Anatomy of the
• C. Basso, M.D., Ph.D. peaceful Lausanne, spared by the second world
Pathological Anatomy, Department of Cardiac, war due to the neutral position of Switzerland, the
Thoracic and Vascular Sciences,
Azienda Ospedaliera-University of Padua
young cardiac pathologist Mahaim wrote an
Medical School, via A. Gabelli, 61, Padua 35121, Italy extraordinary book, that was a collection of per-
e-mail: gaetano.thiene@unipd.it sonal observations at postmortem as well as of
C. Basso et al. (eds.), Cardiac Tumor Pathology, Current Clinical Pathology, 1

DOI 10.1007/978-1-62703-143-1_1, © Springer Science+Business Media New York 2013
2 G. Thiene et al.
Fig. 1.1 Portrait of

Realdo Colombo, Faculty
of Medicine Hall,
-University of Padua.
Reprinted with permission
of the Italian Society of
Cardiology
literature review, and represented a milestone coeur”), the most frequent cardiac tumor (nearly
publication on the topic of cardiac tumors for two-thirds of primary heart neoplasms), he said
several generations of pathologists and physicians “…surgical resection of atrial polyp encounters
involved in the field. From him we learned that apparently unsurmountable difficulties. However,
cardiac myxoma (called in French “le polype” due we should not give up because of this feeling. In
to its resemblance to a pedunculated gastro-enteric any field of science, with technological progress,
polyp), can have a clinical presentation with syn- the impossible is just a moment during the evolu-
cope or dyspnea due to atrio-ventricular valve tion of our powers. As Mummery said about alpin-
orifice occlusion (functional mitral stenosis), with ism, the inaccessible peak becomes an easy route
peripheral artery occlusion due to embolic phe- for ladies…” [4].
nomena, or can be totally asymptomatic being an On the contrary, in 1951 Prichard manifested
incidental finding (“les polypes silencieux”). a pessimistic attitude by saying “…of the surgi-
Although these were all autopsy cases, Mahaim cal treatment of these tumours we never heard”
was optimist on the perspectives of Medicine. [2]. Surprisingly, in the same year 1951 Goldberg
While treating atrial myxoma (“Le polype du et al. [5] for the first time successfully made a
1 Cardiac Tumors: From Autoptic Observations to Surgical Pathology… 3
Fig. 1.2 Title page of the book by Ivan Mahaim on cardiac tumors, published in 1945. Reprinted with permission of
the Italian Society of Cardiology
clinical diagnosis of left atrial myxoma using finding, thereafter they became almost exclu-
angiography and in 1954 Crafoord resected a sively a clinical and surgical observation.
myxoma using extracorporeal circulation [6]. The role of the pathologists is now to establish
Thus, the era of “surgical pathology” started the nature of the resected mass (non-neoplastic,
with clinical diagnosis mostly based upon angiog- benign, or malignant neoplasms) and, last but not
raphy (Fig. 1.3) and the pathologist on call to least, to make the differential diagnosis with sec-
establish in vivo the nature and histotype of the ondary neoplasms. The advent of immunohis-
neoplasm, as in any other field of oncology. tochemistry to characterize the antigenic markers,
However, the historical watershed in the diag- by using monoclonal and polyclonal antibodies,
nosis and treatment came in the 1980s, with the leads to major advances in the diagnosis of pri-
advent of non-invasive imaging, i.e., echocar- mary and secondary cardiac tumors as in other
diography (Fig. 1.4) which, together with com- fields of oncology, but particularly of malignant
puted tomography and cardiac magnetic primary sarcomas, where the tumor cell of origin
resonance (MRI), substantially improved diag- can be the endothelial cell, fibroblast, cardiomyo-
nosis and subsequent treatment. It is possible to cyte, smooth muscle cell, adipocyte, etc. [7].
easily visualize cardiac tumors at the first onset We report some anecdotal cases collected
of symptoms or even incidentally, during routine along the last 35 years at our center in Padua,
diagnostic procedures, and send the patient which are emblematic of the historical evolution
promptly to the surgeon for resection with a in the field of cardiac oncology.
nearly 100% success in the benign forms. Before In 1976 a 61 -year-old man died during
the 1980s cardiac myxomas were a postmortem angiographic examination performed due
4 G. Thiene et al.
Fig. 1.3 Angiographic diagnosis of right ventricular Society of Cardiology. (a) Angiographic image showing a
myxoma in a 21- year-old male (from Bortolotti et al. [20] contrast medium defect at the level of the right outflow
modified). Reprinted with permission of the Italian tract. (b) At surgery, a bi-lobated myxoma was found
Fig. 1.4 Diagram

illustrating a left atrial
myxoma as viewed in the
long-axis parasternal
view by two-dimensional
echocardiography.
Reprinted with permission
of the Italian Society
of Cardiology
Fig. 1.5 A 61-year-old man who died due to acute pul- available in the book by Mahaim (observation by Ferrari
monary edema in 1976. (a) A giant left atrial, cluster- E. Sui tumori poliposi dell’endocardio atriale. Arch Sc
shaped myxoma was found occupying the left Mediche 1941;72:75). Reprinted with permission of the
atrio-ventricular valve orifice. (b) A similar drawing is Italian Society of Cardiology
to acute pulmonary edema and peripheral In 1978, a 15-year-old boy had a diagnosis of
embolisms. The need to wait for angiography myocarditis due to chest pain with cardiac
before referring the patient to surgery resulted enzymes release and ST segment elevation on 12
to be fatal. A giant villous left atrial myxoma lead ECG. Discharged at home 20 days later, he
occupied the mitral atrio-ventricular orifice, suffered an embolic stroke while playing soccer
herniating and protruding into the left ventricle and died suddenly. Autopsy examination revealed
(Fig.1.5). a bi-atrial myxoma (Fig. 1.7a, b) with myxoma-
In 1979 a 45- year-old man suffered a sudden tous embolisms of the cerebral and right coronary
left leg ischemia. An embolus was retrieved by artery, the latter being the cause of the previously
Fogarty, and histology showed the a thrombotic misdiagnosed inferior myocardial infarction
composition. Two days later the patient had an (Fig. 1.7c). Again, echocardiography examina-
embolic “storm,” including the cerebral arteries tion should have identified the cardiac mass, with
and died. At autopsy a smooth left atrial myxoma, prompt indication to surgical resection thus pre-
covered by a stratified thrombus as the probable venting the second fatal embolic episode.
source of multiple embolisms, was found (Fig. 1.6). In 1979, a 43- year-old man, brother of a
Since then, we learned that the true nature of the distinguished surgeon at the University of Padua,
embolic source cannot be derived with certainty complained of malaise and leg arthralgias.
from the histological examination of emboli frag- Although the brother reassured him by saying that
ments alone. An echocardiographic examination he was only stressed, the patient asked a chiro-
should have been performed to look at the heart mancer who, by massaging his legs, told that
and save the life of the patient by emergency oper- his problems came from far away, i.e., from the
ation to resect the embolic source. heart. Few days later, he suffered bi-lateral leg
6 G. Thiene et al.
Fig. 1.6 A 45- year-old man who died in 1979 after several (only thrombus). (b) Drawing of a left atrial myxoma in
episodes of peripheral embolism. (a) A left atrial myxoma the book by Mahaim, herein described as a “pedunculated
was found at autopsy (“polyp”) with the endocardial surface polyp” accounting for functional mitral stenosis. Note the
covered by thrombus. Histological examination of periph- similarity between the two cases. Reprinted with permission
eral embolisms retrieved during life was negative for myxoma of the Italian Society of Cardiology
ischemia and the infra-renal abdominal aorta tion of a huge villous myxoma from the left
appeared occluded at angiography. At emer- atrial cavity (Fig. 1.8).
gency vascular surgery, a big white–gray Some anecdotal cases belong also to the so-
embolus, of gelatinous consistency in keeping called echocardiographic era.
with myxomatous material at histology, was A 6- year-old boy suffered a stroke with
retrieved from the aortic carrefour. At angiog- hemiplegia and echocardiographic examination
raphy, a left atrial mass was found and cardiac detected a left atrial mass. The surgically
surgery was immediately performed with resec- resected mass revealed to be at histology a vil-
Fig. 1.7 A 15-year-old boy who died due to cerebral left atrial myxoma; (b) villous right atrial myxoma, cov-
embolism after a “myocarditis-like” presentation (from ered by thrombi; and (c) right coronary artery occluded by
Valente and Montaguti [24] modified). Reprinted with myxomatous embolism (Alcian PAS ×15)
permission of the Italian Society of Cardiology. (a) Villous
8 G. Thiene et al.
Medical School and the thaumaturgical power of

the Saint!
After the implementation of non-invasive car-
diac imaging and with the exponential increase of
in vivo diagnosis and “surgical pathology” cases,
we did not observe anymore autopsy deaths due
to cardiac myxomas along the natural history.
The rare postmortem observations were incidental
findings of tumors of small size or of myxoma
with calcific involution, a condition for whom we
coined the term “lithomyxoma” [8] (Fig. 1.11).
On the contrary, the availability of echocar-
diography performed as a routine/screening test
in several conditions due to its non-invasive-
ness, led to the frequent casual identification of
many small benign endocavitary tumors, par-
ticularly fibroelastomas (or fibroelastic papillo-
mas). When localized in the left chambers,
surgical resection is always indicated, for pri-
mary prevention of embolic phenomena. On the
contrary, right-sided papillomas can be fol-
lowed up.
Fig. 1.8 A 43-year-old man with villous left atrial myx- Malignant cardiac tumors represent a different
oma accounting for leg ischemia with abdominal aortic clinico-pathologic challenge.
carrefour occlusion. The vascular surgeon removed a sau-
sage-like huge mass, which resulted to be an embolus Secondary metastatic tumors can involve the
detached from the left atrial myxoma, as identified by car- pericardium, myocardium, and endocardium. In
diac angiography and then surgically resected (from the latter instance, endocardial metastases may
Ballotta et al. [18] modified). Reprinted with permission be also observed of such a size to create endo-
of the Italian Society of Cardiology
cavitary obstruction like primary cardiac tumors
(Fig. 1.12). Noteworthy, the diagnosis of second-
lous, gelatinous, and friable myxoma (Fig. 1.9). ary cardiac mass is no so rarely achieved only by
During the follow-up, the boy well recovered histological examination of the resected cardiac
without neurological sequelae. Since then, mass that reveals a histotype different from that
echocardiography is always performed in any of primary malignant cardiac tumors. For
patient, even in the pediatric age, with neuro- instance, we recall a case of a right atrial endo-
logical or syncopal episodes, to exclude a car- cavitary villous tumor, labeled as myxoma at
diac source. naked eye observation and then diagnosed as tes-
A 47- year-old woman coming from the South tis corion carcinoma after histological and immu-
of Italy to Padua as devotee of Saint Antony, went nohistochemical investigation; as well as the case
to the Church in Padua with malaise and arthral- of a right atrial mass located at the orifice of the
gias; while kneeling to Saint Antony, she had loss inferior caval vein, subsequently diagnosed as
of consciousness and fainted. Promptly transferred clear cell renal carcinoma (Fig. 1.13). In both
to the Intensive Care Unit in Padua, echocardiog- instances, a total body imaging (echo, CT) has
raphy disclosed a left atrial mass wedging into been then performed with discovery of the pri-
the mitral valve orifice (Fig. 1.10). She had emer- mary malignant tumors and orchiectomy and
gency operation and survived without any com- nephrectomy were carried out, respectively, with
plication: a joint venture between the Patavian adjuvant chemotherapy.
Fig. 1.9 Left atrial myxoma in a 6-year-old child with cerebral stroke and hemiplegia. Two-dimensional echocardiography
revealed a left atrial mass (a). At surgical pathology examination, a friable, villous left atrial myxoma was diagnosed (b).
Reprinted with permission of the Italian Society of Cardiology
Primary malignant cardiac tumors are mostly or the pulmonary artery, mimicking pulmonary
infiltrating masses with inherent difficulties in embolism. Histological examination of the resected
achieving a complete surgical resection and as “embolus” is mandatory, to assess the benign or
such with a poor prognosis. An exception is repre- malignant nature of the process and characterize
sented by the rare primary malignant cardiac the histotype [7].
tumors with an endocavitary growth and a clinical In the last two decades, there have been many
presentation mimicking myxoma due to obstruc- steps forward in the clinical diagnosis and treat-
tive symptoms and signs. The patient can even ment of cardiac tumors:
present with cardiogenic shock, when the intrac- 1. Endomyocardial biopsy. Tissue sampling to
ardiac mass occupies the atrio-ventricular orifices assess the neoplastic nature of the mass during
10 G. Thiene et al.
Fig. 1.10 A 47-year-old woman with syncopal episodes. The prompt echocardiographic examination (a, b) detected a
polypous left atrial mass, impinging during diastole into the mitral valve orifice. The successfully resected mass revealed
to be a smooth myxoma (“polyp”) (c). Reprinted with permission of the Italian Society of Cardiology
life can be achieved through either surgical for diagnosis, allowing therapeutic planning,
thoracotomy or endomyocardial biopsy. With including cardiac transplantation, in cases of
the latter technique, tissue samples may be malignant neoplasm without extra-cardiac
taken with the bioptome introduced antegrade metastasis. Moreover, endomyocardial biopsy
in the right cardiac chambers either through can be useful in the setting of tumors which
femoral or jugular veins or, more rarely, retro- are unresectable or require histological char-
grade in the left chambers through femoral acterization before chemotherapy is started,
arteries [9]. The procedure is under echocar- such as lymphomas. An adequate number and
diographic guidance and avoids thoracotomy size of samples (4–5 pieces, 1–2 mm each) is
Fig. 1.11 Incidental autopsy finding of left atrial myxoma with calcific involution (lithomyxoma) in a 72-year-old
woman who died due to ischemic heart disease (from Basso et al. [8] modified). Reprinted with permission of the Italian
Society of Cardiology. (a) gross view; (b) ex vivo X-Ray
usually enough for a thorough histological consist mostly of teratomas, fibromas, rhab-
investigation, including immuno-histochemis- domyomas either intramural or endocavitary,
try, to achieve a precise diagnosis (Fig. 1.14). and more frequent indications include arrhyth-
2. Prenatal echocardiographic diagnosis. mias, hydrops, retarded intrauterine growth,
Nowadays, prenatal echography is a routine and familiarity of tuberous sclerosis. Prenatal
examination during pregnancy and the request diagnosis is essential to plan the surgical inter-
for fetal echocardiography is increasing. Many vention soon after delivery.
congenital heart diseases are diagnosed before 3. Cardiac transplantation. Organ replacement
birth, including cardiac tumors [10]. They with orthotopic cardiac transplantation is an
12 G. Thiene et al.
Fig. 1.12 Huge endocavitary right atrial mass, herniating into the tricuspid valve orifice in a 77- year-old man with a
history of cirrhosis. At histology, a metastasis of hepatocarcinoma was identified. Reprinted with permission of the
Italian Society of Cardiology
Fig. 1.13 Right atrial mass with pre-operative diagnosis with round nuclei and vacuolated cytoplasm, aggregated in
of cardiac myxoma in a 42- year-old woman. cordon-like structures are visible (hematoxylin–eosin). (c)
Reprinted with permission of the Italian Society of At immunohistochemistry, a few cells are positive for
Cardiology. ( a ) Gross view of the surgically resected vimentin. A final diagnosis of cardiac metastasis of clear
mass with a smooth surface. (b) At histology, clear cells cell renal carcinoma was done
Fig. 1.14 Histologic diagnosis of cardiac metastasis by is visible (arrows). (b) Right ventricular endomyocardial
T-cell lymphoma through endomyocardial biopsy in a biopsy shows a lympho-proliferative lesion infiltrating the
36- year-old woman (from Testolin et al. [40] modified). myocardium. (c) At immunohistochemistry, the cells are
Reprinted with permission of the Italian Society of positive for T lymphocytes (CD3) (AML anterior mitral
Cardiology. (a) Trans-esophageal echocardiography, four- leaflet, CVC central venous catheter, RA right atrium, RV
chamber view: a mass on both side of the interatrial septum right ventricle, LA left atrium, LV left ventricle)
extreme therapeutic option which is indicated 4. Cardiac magnetic resonance imaging (MRI)
in the setting of non-resectable benign cardiac and computed tomography (CT). MRI is the
tumors, or in cases of infiltrating primary best available non-invasive procedure for
malignant neoplasms without extra-cardiac cardiac tumor diagnosis in terms of site, mor-
metastasis. The ideal situation is typically phology, dimensions, extension, topographic
represented by cardiac fibroma, which is usu- relations, and infiltration of surrounding struc-
ally located within the interventricular septum tures. It may also help for tissue characteriza-
(Fig. 1.15) or the left ventricular free wall tion (adipose tissue, necrosis, hemorrhage,
[10]; total heart removal with ex vivo repair on vascularization, calcification), although the
the bench, followed by auto-transplant, can be specificity is still low [11]. A “probabilistic”
also carried out. A different situation is repre- histopathological diagnosis is more reliable
sented by infiltrating primary malignant cardiac and the term “mass” should be employed,
tumors, where cardiac transplantation is consid- leaving the final answer to histology. In case
ered only in the absence of metastases. However, of lipoma, with hyper-intensity signal in T1
the cardiac surgeon has always to take into imaging, the precise histotype may be estab-
consideration the low number of donors and lished by MRI, with a very high diagnostic
the high number of patients in the waiting list probability. Use of contrast medium may be of
with a potentially better long-term prognosis. help to detect highly vascularized tumors, like
14 G. Thiene et al.
Fig. 1.15 A 40-year-old woman, with echocardiographic (a) Long axis section of the native heart showing a huge
diagnosis of asymmetric hypertrophic cardiomyopathy, oval shape whitish mass occupying the interventricular
underwent cardiac transplantation due to refractory septum and accounting for subaortic bulging/obstruction.
congestive heart failure (from Valente et al. [10]). Reprinted (b) At histology, a cardiac fibroma was diagnosed
with permission of the Italian Society of Cardiology. (Heidenhain trichrome)
Fig. 1.16 (a) Rheumatic mitral valve stenosis with left went mitral valve replacement). (b) Similar drawing in the
atrial ball-thrombus, mimicking a myxoma (a 72- year-old original book by Mahaim. Reprinted with permission of
woman with history of peripheral embolism who under- the Italian Society of Cardiology
myxomas, angiomas, and angiosarcomas. In detection of cardiac masses, whereas MRI and
case of fibroma, delayed contrast enhance- CT may be complementary tools, with their
ment shows homogeneous uptake of gadolin- own advantages and limitations. Due to their
ium, indicating fibrous tissue. non-invasiveness and lack of radiation, two-
Multi-slice CT has the advantage of a better dimensional echo and MRI are also the gold
spatial resolution in case of possible lung, pleural, standard for follow-up studies.
and mediastinal involvement. Moreover,
calcification is easily detected within the mass
and may point to fibroma, in case of mural mass, Non-neoplastic Cardiac Masses
myxoma in case of an intracavitary atrial mass in
the elderly, or teratoma in case of pericardial Only histological examination may establish
mass in infancy. MRI and CT can also differenti- whether a cardiac mass is neoplastic in nature,
ate serous from hemorrhagic pericardial effusion. either benign or malignant. When seen by clini-
However, multi-slice CT does not allow to cal imaging, the use of term “mass” is advisable,
fully investigate involvement of cardiac valves, since it may have several explanations other than
and presents the limitation of high dosage radia- cardiac tumors.
tion, so as to preclude its employment in the fol- 1. Thrombi. An isolated mass inside an atrial
low-up of young subjects. Fast heart rates and appendage is almost exclusively a thrombus. In
arrhythmias may jeopardize the quality of imag- the left atrium, free floating masses like “ball
ing of both MRI and multi-slice CT. thrombus” should point to a mitral valve pathol-
Obviously, two-dimensional echocardiography ogy, usually rheumatic in origin (Fig. 1.16).
remains the first diagnostic approach for However, differential diagnosis with left atrial
16 G. Thiene et al.
mimic valve papillary fibroelastoma. Valvular

and non-valvular endocardial thrombosis may
be observed in antiphospholipid syndrome [12].
Histological investigation is always needed to
achieve the final diagnosis [13] (Fig. 1.19).
2. Cardiomyopathies. Endocardial fibroplastic
Loeffler endocarditis is a restrictive (oblitera-
tive) cardiomyopathy, usually associated
with eosinophilia, hypersensitivity, or eosino-
philic leukemia, consisting of a mural throm-
bus filling the apical and inflow portions of
the ventricles to such an extent to entrap the
mitral and/or tricuspid valves apparatus.
Cardiac imaging may mis-diagnose an apical
form of hypertrophic cardiomyopathy or an
endocardial tumor. Endomyocardial biopsy
with tissue characterization may be of help
for differential diagnosis (Fig. 1.20).
3. Infections. Infective vegetations of cardiac
valves may mimic papillary fibroelastoma,
and sometimes at the mitral level they may be
so huge as to simulate embolizing atrial myx-
oma. Free floating masses may not necessarily
be thrombotic, but even septic (fungal in
immunosuppressed patients) (Fig. 1.21).
Pericardial or myocardial cysts may be hydatid
cysts by echinococcosis, to be treated cau-
tiously during the surgery to avoid rupture and
spread of infection (Fig. 1.22).
4. Calcium. Calcium stones, intramural or intra-
cavitary, may occur and not necessarily are
the outcome of dystrophic calcification of
previous infections/tumors, as in the case of
lithomyxoma. The phenomenon may be so
massive to transform the heart into a sort of
Fig. 1.17 A 61- year-old man with pulmonary a stone quarry. Dystrophic calcification of
edema. Reprinted with permission of the Italian
the mitral valve annulus can also account
Society of Cardiology. ( a ) Two-dimensional echocar-
diography, four-chamber view shows a mass occupy- for misdiagnosis of an atrio-ventricular mass
ing the mitral valve ori fi ce. ( b ) At surgery, a myxoma by echocardiography. Endocavitary calcific
with strangulation corresponding to the sphincter masses have been reported even in the pediat-
contraction of the mitral valve anulus is found
ric age as a consequence of calcific involution
of thrombi upon central venous catheters.
myxoma is always needed (Fig. 1.17). Small The single center experience collected at the
mural thrombi may be observed at the apex of University of Padua since 1970, when the first
the left ventricle, even in the setting of a pre- surgical intervention for resection of a cardiac
served contractility, and misinterpreted clini- myxoma was accomplished [15], is witnessed by
cally as left ventricular myxomas (Fig. 1.18). the numerous publications on the topic, available
Non-bacterial thrombotic endocarditis may in the literature [16–55].
Fig. 1.18 A 33 -year-old woman with recurrent left ven- chamber view (LA left atrium, LV left ventricle, RA right
tricular apex thrombosis, mimicking a endocardial tumor. atrium, RV right ventricle). (b) At histology, the resected
Reprinted with permission of the Italian Society of mass consists of thrombotic material (Heidenhain
Cardiology. (a) Two-dimensional echocardiography, four- trichrome)
18 G. Thiene et al.
Fig. 1.19 A 20-year-old patient with a small left ven- RA right atrium, RV right ventricle). (b) Gross view of the
tricular apical mass (from Basso et al. [12] modified). surgically resected mass: note the smooth surface and the
Reprinted with permission of the Italian Society of pink color. (c, d) At histology and immunohistochemistry,
Cardiology. (a) Two-dimensional echocardiography, api- the benign proliferation shows a myxoid background with
cal four-chamber view shows a round mass at the left ven- vessel proliferation in keeping with myxomatous angioma
tricular apex (arrow) (LA left atrium, LV left ventricle, (hematoxylin–eosin and CD31)
Fig. 1.20 A 61- year-old man affected by Loeffler retrieved by endomyocardial biopsy, two of which
fibroplastic endocarditis (from Basso et al. [36] consist of thrombotic material (hematoxylin–eosin).
modified). Reprinted with permission of the Italian (c) One of the endomyocardial biopsy samples shows
Society of Cardiology. (a) Left ventricular angiogra- endocardial fibrous thickening (Heidenhain trichrome).
phy showing a contrast medium defect at the apex cor- (d) At higher magnification, eosinophilic infiltrates are
responding to a round oval mass. (b) Four samples visible (hematoxylin–eosin)
Fig. 1.21 A 23-year-old man under chemotherapic ther- left ventricular cavity (A aspergilloma, Ao aorta, LA left
apy due to acute myeloid leukemia (from Vida et al. [14] atrium, LV left ventricle); (c) the resected whitish mass
modified). Reprinted with permission of the Italian shows a small pedicle and a rough surface; (d) at histology,
Society of Cardiology. (a, b) at two-dimensional echocar- fungal hyphas are detected (Alcian PAS)
diography, a free-floating round mass is visible within the
Fig. 1.22 Echinococcus cyst is surgically removed from the paricardial cavity in a 55- year-old man (a). At histology,
the external membrane and the scolices inside the cyst are appreciable (b, hematoxylin–eosin). Reprinted with permis-
sion of the Italian Society of Cardiology
19. Stritoni P, Daliento L, Fasoli G, Schivazappa L, Chioin

References R, Fusaro A, Casarotto D, Bortolotti U, Valente M,
Thiene G. Mixoma atriale. Esperienza clinica, diag-
1. Columbus MR. De Re Anatomica, Libri XV. Venice: nostico-strumentale, chirurgica e patologica in 13
N Bevilacque,1559, p 269. casi. G Ital Cardiol. 1979;9:1001–16.
2. Prichard RW. Tumors of the heart: review of the sub- 20. Gallucci V, Stritoni P, Fasoli G, Thiene G. Giant blood
ject and report of 150 cases. Arch Pathol. cyst of tricuspid valve. Successful excision in an
1951;51:98–128. infant. Br Heart J. 1976;38:990–2.
3. Wold LE, Lie JT. Cardiac myxomas: a clinicopatho- 21. Bortolotti U, Mazzucco A, Valfrè C, Valente M,
logic profile. Am J Pathol. 1980;101:219–40. Pennelli N, Gallucci V. Right ventricular myxoma:
4. Mahaim I. Le tumeurs et les polypes du coeur: etude review of the literature and report of two patients. Am
anatomoclinique. Paris: Masson; 1945. Thorac Surg. 1982;33:277–84.
5. Goldberg HP, Glenn F, Dotter CT, Steinberg I. 22. Stellin G, Bortolotti U, Valfré C, Mazzucco A, Thiene
Myxoma of the left atrium: diagnosis made during life G, Cavarzerani A, Gallucci V. Mural papilloma of the
with operative and post-mortem findings. Circulation. left ventricle and floppy mitral valve: report of an
1952;6:762–7. unusual association. Texas Heart Inst J.
6. Crafoord C. Panel discussion on late results of mitral 1983;10:89–92.
commissurotomy. In: Lam CR, editor. International 23. Valente M. Structural profile of cardiac myxoma.
symposium on cardiovascular surgery. Philadelphia, Appl Pathol. 1983;1:251–63.
PA: Saunders; 1955. p. 161–78 24. Valente M, Montaguti A. Il mixoma cardiaco
7. Basso C, Valente M, Poletti A, Casarotto D, Thiene G. nell’adolescenza. Studio anatomo-patologico in tre
Surgical pathology of primary cardiac and pericardial pazienti. Pathologica. 1984;76:323–32.
tumors. Eur J Cardiothorac Surg. 1997;12:730–7. 25. Livi U, Bortolotti U, Milano A, Valente M, Prandi A,
8. Basso C, Valente M, Casarotto D, Thiene G. Cardiac Frugoni C, De Mozzi P, Valfré C, Mazzucco A,
lithomyxoma. Am J Cardiol. 1997;80:1249–51. Gallucci V. Cardiac myxomas: results of 14 years
9. Poletti A, Cocco P, Valente M, Fasoli G, Chioin R, experience. Thorac Cardiovasc Surg. 1984;32:143–7.
Thiene G. In vivo diagnosis of cardiac angiosarcoma 26. Thiene G, Valente M. I tumori primitivi del cuore e
by endomyocardial biopsy. Cardiovasc Pathol. del pericardio nell’esperienza dell’Istituto di Anatomia
1993;2:89–91. Patologica dell’Università di Padova (1972–1984). In:
10. Valente M, Cocco P, Thiene G, Casula R, Poletti A, Pansini R, editors. Progressi Clinici: Medicina.
Milanesi O, Fasoli G, Livi U. Cardiac fibroma and Padova: Piccin Ed., 1985;2/2–3: p. 169–207.
heart transplantation. J Thorac Cardiovasc Surg. 27. Bortolotti U, Mazzucco A, Rubino M, Maraglino G,
1993;106:1208–12. Sturaro M, Milano A, Stellin G, Thiene G, Gallucci V.
11. Hoffmann U, Globits S, Schima W, Loewe C, Puig S, I mixomi dell’atrio destro. Tecnica operatoria, risul-
Oberhuber G, Frank H. Usefulness of magnetic reso- tati e follow-up a distanza. Chir Torac.
nance imaging of cardiac and paracardiac masses. Am 1989;42:371–2.
J Cardiol. 2003;92:890–5. 28. Mazzucco A, Bortolotti U, Thiene G, Dan M, Stritoni
12. Basso C, Fasoli G, Casarotto D, Thiene G. Unusual P, Scutari M, Stellin G. Left ventricular papillary
left ventricular mass. Circulation. 1998;98:1036–7. fibroelastoma with coronary embolization. Eur J
13. Basso C, Bottio T, Rubino M, Ruffatti A, Pittarello D, Cardio-Thorac Surg. 1989;3:471–3.
Thiene G, Gerosa G. Antiphospholipid sindrome and 29. De Dominicis E, Frigiola A, Thiene G, Menicanti L,
right atrial mass. J Thorac Cardiovasc Surg. Bozzola L, Finocchi G. Subaortic stenosis by solitary
2005;130:1462–3. rhabdomyoma. Successful excision in an infant fol-
14. Vida V, Biffanti R, Thiene G, Stellin G, Milanesi O, lowing 2D echocardiogram and Doppler diagnosis.
Basso C. Left ventricular mass after treatment with Chest. 1989;95:470–2.
chemotherapic drugs. Circulation. 2004;109:e300–1. 30. Bortolotti U, Maraglino G, Rubino M, Santini F,
15. Casarotto D. Mixoma dell’atrio sinistro. Chirurgia Mazzucco A, Milano A, Fasoli G, Livi U, Thiene G,
Triveneta. 1971;11:279–87. Gallucci V. Surgical excision of intracardiac myxo-
16. Thiene G, Miraglia G, Menghetti L, Nava A, Rossi L. mas: a 20-year follow-up. Ann Thorac Surg.
Multiple lesions of the conduction system in a case of 1990;49:449–53.
cardiac rhabdomyosarcoma with complex arrhyth- 31. Bortolotti U, Faggian G, Mazzucco A, Milano A,
mias. An anatomic and clinical study. Chest. Thiene G, Fasoli G, Gallucci V. Right atrial myxoma
1976;70:378–81. originating from the inferior vena cava. Ann Thorac
17. Casarotto D, Bortolotti U, Russo D, Betti D, Surg. 1990;49:1000–2.
Schivazappa L, Thiene G. Surgical removal of a left 32. Cocco P, Valente M, Thiene G. I tumori primitivi del
atrial myxoma during pregnancy. Chest. cuore nell’era cardiochirurgica: dall’autopsia al trapi-
1979;75:390–2. anto cardiaco. Riv Anat Pat Oncol.
18. Ballotta E, Thiene G, Valente M, Deriu GP. Mixoma 1991;49–50:135–72.
dell’atrio sinistro rivelato da un’occlusione acuta del 33. Mazzucco A, Faggian G, Bortolotti U, Bonato R,
carrefour aortico. G Ital Cardiol. 1979;9:627–30. Pittarello D, Centonze G, Thiene G. Embolizing
22 G. Thiene et al.
papillary fibroelastoma of the mitral valve. Texas echocardiographic assessment. J Thorac Cardiovasc
Heart Inst J. 1991;18:62–6. Surg. 2004;128:767–9.
34. Valente M, Basso C, Thiene G, Bressan M, Stritoni P, 47. Bottio T, Pittarello D, Bonato R, Thiene G, Gerosa G,
Cocco P, Fasoli G. Fibroelastic papilloma: a not-so- Casarotto D, Basso C. Echocardiographic diagnosis of
benign cardiac tumor. Cardiovasc Pathol. 1992;1:161–6. aortic valve papillary fibroelastoma. Tex Heart Inst J.
35. Basso C, Stefani A, Calabrese F, Fasoli G, Valente M. 2004;31:322–323
Primary right atrial fibrosarcoma diagnosed by endo- 48. Vida V, Cerutti A, Thiene G, Stellin S, Milanesi O,
cardial biopsy. Am Heart J. 1996;131:399–402. Basso C. Calcified mass in the right atrium. Ann
36. Basso C, Poletti A, Valente M, Thiene G. Diagnosi di Thorac Surg. 2005;79:717.
tumore cardiaco tramite biopsia endomiocardica. 49. Padalino M, Basso C, Milanesi O, Vida VL, Svaluto
In: Baroldi G, Thiene G, editors. Testo Atlante Moreolo G, Thiene G, Stellin G. Surgically treated
Biopsia Endomiocardica. Padova: Piccin Ed; 1996. p. primary cardiac tumors in early infancy and child-
178–96. hood. J Thorac Cardiovasc Surg. 2005;129:1358–63.
37. Basso C, Valente M, Poletti A, Casarotto D, Thiene G. 50. Mazzola A, Spano JP, Valente M, Gregorini R, Villani
Surgical pathology of primary cardiac and pericardial C, Di Eusanio M, Ciocca M, Minuti U, Giancola R,
tumors. Eur J Cardio-thorac Surg. 1997;12:730–8. Basso C, Thiene G. Leiomyosarcoma of the left
38. Scalia D, Basso C, Rizzoli G, Lupia M, Budano S, atrium mimicking a left atrial myxoma. J Thorac
Thiene G, Venturini A. Should right-sided fibroelastomas Cardiovasc Surg. 2006;131:224–6.
be operated upon? J Heart Valve Dis. 1997;6:647–50. 51. Thiene G, Valente M, Lombardi M, Basso C. Tumours
39. Basso C, Barbazza R, Thiene G. Lipomatous hypertro- of the heart. In: Camm JA, Luscher TF, Serruys PV,
phy of the atrial septum. Circulation. 1998;97:1423. editors. ESC textbook of cardiovascular medicine.
40. Testolin L, Basso C, Pittarello D, Casarotto D, Valente Oxford: Oxford University Press; 2009.
M. Cardiogenic shock due to metastatic cardiac lym- 52. Rickelt S, Rizzo S, Doerflinger Y, Zentgraf H, Basso
phoma: still a diagnostic and therapeutic challenge. C, Gerosa G, Thiene G, Moll R, Franke WW. A novel
Eur J Cardiothorac Surg. 2001;19:365–8. kind of tumor type-characteristic junction: plakophi-
41. Bottio T, Basso C, Rizzoli G, Casarotto D, Thiene G. lin-2 as a major protein of adherens junctions in car-
Case report: fibroelastoma of the papillary muscle of diac myxomata. Mod Pathol. 2010;23:1429–37.
the mitral valve: diagnostic implications and review 53. Padalino MA, Vida VL, Bhattarai A, Reffo E, Milanesi
of the literature. J Heart Valve Dis. 2002;11:288–91. O, Thiene G, Stellin G, Basso C. Giant intramural left
42. Basso C, Valente M, Thiene G. Aspetti anatomo- ventricular rhabdomyoma in a newborn. Circulation.
clinici dei tumori del cuore e del pericardio. In: 2011;124:2275–7.
Crepaldi G, Baritussio A, editors. Trattato di Medicina 54. Perazzolo M, Thiene G, De Lazzari M, Calabrese F,
Interna: Malattie del cuore e dei vasi. Padova: Piccin Lacognata C, Rizzo S, Cacciavillani L, Tona F,
Editore; 2002. p. 757–68. Corbetti F, Iliceto S, Basso C. Concealed metastatic
43. Padalino MA, Basso C, Thiene G, Stellin G. Images lung carcinoma presenting as acute coronary syn-
in cardiovascular medicine: Giant right ventricular drome with progressive conduction abnormalities.
fibroma in an infant. Circulation. 2002;106:386. Circulation. 2012;125:e499–502.
44. Padalino MA, Basso C, Moreolo GS, Thiene G, 55. Padalino MA, Vida VL, Boccuzzo G, Tonello M,
Stellin G. Left atrial myxoma in a child: case report Sarris GE, Berggren H, Comas JV, Di Carlo D, Di
and review of the literature. Cardiovasc Pathol. Donato RM, Ebels T, Hraska V, Jacobs JP, Gaynor
2003;12:233–6. JW, Metras D, Pretre R, Pozzi M, Rubay J, Sairanen
45. Basso C, Bottio T, Valente M, Bonato R, Casarotto D, H, Schreiber C, Maruszewski B, Basso C, Stellin G.
Thiene G. Primary cardiac valve tumours. Heart. Surgery for primary cardiac tumors in children: early
2003;89:1259–60. and late results in a multicenter European congenital
46. Rizzoli G, Bottio T, Pittarello D, Napodano M, Thiene heart surgeons association study. Circulation.
G, Basso C. Atrial septal mass: transesophageal 2012;126:22–30.
Cardiac Tumors: Classification
and Epidemiology 2
Gaetano Thiene, Cristina Basso, Stefania Rizzo,
Gino Gerosa, Giovanni Stellin,
and Marialuisa Valente
advent of cardiac surgery, it became a referral

Introduction center for diagnostic and therapeutic purposes,
the autopsy prevalence had a threefold increase
The precise prevalence of primary cardiac tumors up to 0.17%, in the time interval 1954–1970 [2].
in the general population is still unknown and is As far as secondary cardiac tumors, an investi-
based on old postmortem studies. gation performed at our University in the time
In a study of 12,485 autopsies carried out in interval 1967–1976 revealed that among 7,460
the time interval 1972–1991, Lam et al. reported autopsies the cause of death was malignancies in
a rate of 0.056% for primary (56 cases per 1,181 cases (15.33%) [3], in 74 of which cardiac
100,000 autopsies), and of 1.23% for secondary metastases occurred. This accounted for 1% of all
tumors (123 cases per 10,000 autopsies) [1]. autopsies and 6% of those with malignancies.
However, epidemiological data are strongly Anyway, it is generally agreed that autopsy
influenced by when and where the data have been prevalence of primary cardiac tumors is 1 out of
collected and do not necessarily reflect the real 2,000 and that of secondary cardiac tumors is 1
incidence in the population. out of 100 autopsies, with a secondary/primary
For instance, at the Mayo Clinic the autopsy cardiac tumors ratio of 20:1.
prevalence of primary cardiac tumors was 0.05%
in the time interval 1915–1930; when, with the
Classification of Cardiac Tumors
G. Thiene, M.D. (*) • C. Basso, M.D., Ph.D.
S. Rizzo, M.D. • M. Valente, M.D. Although a classification of tumors can be based
Pathological Anatomy, Department of Cardiac, Thoracic upon cellular organization (proliferative reaction,
and Vascular Sciences, Azienda Ospedaliera-University hamartoma, cyst, and true neoplasm, either
of Padua Medical School, via A. Gabelli, 61,
Padua 35121, Italy
benign or malignant) or tumor histotype (mesen-
e-mail: gaetano.thiene@unipd.it chymal, epithelial, mesothelial), it is easier to fol-
G. Gerosa, M.D.
low the classic distinction between benign and
Cardiac Surgery, Department of Cardiac, Thoracic and malignant, differentiating cardiac and pericardial
Vascular Sciences, Azienda Ospedaliera-University of tumors [4].
Padua Medical School, via N. Giustiniani, 2, The World Health Organization recently con-
Padua 35128, Italy
vened a group of pathologists to put forward a
G. Stellin, M.D. new classification of primary cardiac tumors
Pediatric Cardiac Surgery, Department of Cardiac,
Thoracic and Vascular Sciences, Azienda Ospedaliera-
(Table 2.1).
University of Padua Medical School, Although some neoplasms or tumor-like
via N. Giustiniani, 2, Padua 35128, Italy lesions have been ignored (cysts of pericardium,

24 G. Thiene et al.
Table 2.1 Histological classification of tumors of the

heart, World Health Organization (from Travis et al. [4]) Malignant Cardiac Tumors, Grading
Benign tumors and tumor-like lesions and Staging
Rhabdomyoma 8,900/0
Histiocytoid cardiomyopathy (Purkinje cell Given their low frequency, there is no grading
tumor)
system for malignant cardiac tumors and we have
Hamartoma of mature cardiac myocytes
to refer to the criteria used for soft tissue neo-
Adult cellular rhabdomyoma 8,904/0
plasms [6]. The main parameters in non-cardiac
Cardiac myxoma 8,840/0
Papillary fibroelastoma
soft tissue tumors are the mitotic index and the
Hemangioma 9,120/0 extent of tumor necrosis [7, 8].
Cardiac fibroma 8,810/0 Three grades of malignancy are usually recog-
Inflammatory myofibroblastic tumor 8,825/1 nized: G1, low grade; G2, intermediate grade;
Lipoma 8,850/0 G3, high grade.
Cystic tumor of the atrioventricular node The FNCLCC (Fédération Nationale des
Malignant tumors Centre de Lutte Contre le Cancer) system is based
Angiosarcoma 9,120/3 on a score obtained by evaluating three features:
Epithelioid hemangioendothelioma 9,133/3 tumor differentiation, mitotic rate, and amount of
Malignant pleomorphic fibrous histiocytoma 8,830/3 tumor necrosis. A score is attributed indepen-
(MFH)/undifferentiated pleomorphic sarcoma dently to each of the three parameters and the
Fibrosarcoma and myxoid fibrosarcoma 8,840/3
final histological grade is the sum of the three
Rhabdomyosarcoma 8,900/3
attributed scores (Table 2.2) [8].
Leiomyosarcoma 8,890/3
As a general rule, grading should be used only
Synovial sarcoma 9,040/3
for untreated primary soft tissue sarcomas and
Liposarcoma 8,854/3
Cardiac lymphoma
should be performed on representative material
Metastatic tumors (for instance, tissue obtained through endomyocar-
Pericardial tumors dial biopsy cannot be used for grading purposes).
Solitary fibrous tumor 8,815/1 Concerning the epidemiology and prevalence
Malignant mesothelioma 9,050/3 of various tumor histotypes, the data are also not
Germ cell tumors uniform in the literature. Being a rare disease, the
Metastatic pericardial tumors published numbers of primary cardiac tumors
frequently reflect a referral bias. This is for
instance the case of the data reported by the series
blood cysts), this classification has the merit of of the Armed Force Institute of Pathology (AFIP)
unifying the terminology. Since cardiac tumors in Washington [9], which remains the most
have been variously named, we will add the syn- quoted histopathology publication on cardiac
onym for each histotype. According to this last tumors, based upon 386 cases of primary cardiac
classification, cardiac tumors are grouped into tumors. The rates of 35% for primary sarcomas
three categories, i.e., benign tumors and tumor- and of only 29% for myxomas, clearly reflect the
like lesions; malignant tumors; and pericardial referral bias of data derived from pathology ter-
tumors. tiary centers, where only the most difficult cases
According to the morphology code of the are sent for expert opinion.
International Classification of Diseases for The difficulty in obtaining real epidemiologi-
Oncology (ICD-0) [5] and the Systematized cal data on primary cardiac tumors is emphasized
Nomenclature of Medicine (http://snomed.org) by the nonreliability of both autopsy and surgical
the biological behavior is coded /0 for benign pathology series, since in the former there is the
tumors, /3 for malignant tumors, and /1 for “bor- selection bias of dead patients during hospitaliza-
derline” or uncertain behavior. tion and in the latter that of indication to surgery
2 Cardiac Tumors: Classification and Epidemiology 25
Table 2.2 Parameters of the grading system for sarcomas of the Féderation Nationale des Centres de Lutte contre le
Cancer (FNCLCC)
Tumor differentiation
Score 1 Sarcomas closely resembling normal adult mesenchymal tissue (e.g., low-grade leiomyosarcoma)
Score 2 Sarcomas for which histological typing is certain (e.g., myxoid fibrosarcoma)
Score 3 Undifferentiated sarcoma, angiosarcoma
Mitotic count
Score 1 0–9 mitoses per 10 HPFa
Score 2 10–19 mitoses per 10 HPFa
Score 3 ³20 mitoses per 10 HPFa
Tumor necrosis
Score 0 No necrosis
Score 1 <50% tumor necrosis
Score 2 ³50% tumor necrosis
Histological grade
Grade 1 (G1) Total score 2, 3
Grade 2 (G2) Total score 4, 5
Grade 3 (G3) Total score 6, 7, 8
Modified from Trojani et al. [8]
a
A high-power field (HPF) measures 0.1734 mm²
(see for instance rhabdomyoma) or tumor resect-

ability (see for instance primary malignant car-
diac tumors with infiltration and metastases).
We herein refer to the clinicopathologic expe-
rience of the University of Padua, Italy in the
time interval 1970–2010.
Epidemiology of Primary Cardiac Fig. 2.1 Primary cardiac and pericardial tumors,
Tumors 1970–2010 at the University University of Padua Medical School (1970–2010): 267
of Padua cases, 239 (89.5%) bioptic and 28 (10.5%) autoptic
In the time interval 1970–2010, 267 primary cardiac

and pericardial tumors have been studied, includ- 10.5%
ing 239 bioptic (89.5%) and 28 autoptic (10.5%)
(Fig. 2.1). This is mostly a biopsy-based experi-
89.5%
ence, thus emphasizing that nowadays cardiac
tumors are uncommonly fatal, with the exception
of the rare primary malignant forms.
Among the consecutive 239 bioptic primary
Benign Malignant
cardiac tumors (135 female, age ranging 1 day–85
years, mean 48 ± 22 years, median 53), only 26 Fig. 2.2 Primary bioptic cardiac and pericardial tumors,
(10.5%) were malignant and 213 (89.5%) benign University of Padua Medical School (1970–2010): 239
(Fig. 2.2). cases, 213 (89.5%) benign and 26 (10.5%) malignant
26 G. Thiene et al.
In eight cases (3.5%) the diagnosis was (15.5%). The various tumor histotypes are illus-
achieved through preoperative biopsy: endomyo- trated in Fig. 2.3.
cardial in four cases (right atrium angiosarcoma Tumor location was the left atrium in eight
in three and fibrosarcoma in one, respectively) (three undifferentiated sarcomas, two leiomyo-
and thoracotomic in four cases (two right ven- sarcomas, one fibrosarcoma, one malignant
tricular fibromas, one left ventricular heman- fibrous histiocytoma, and one malignant schwan-
gioma, and one left atrial malignant schwannoma). noma); the right atrium in eight (five angiosarco-
Cardiac transplantation was performed in three mas, one B cell lymphoma, one fibrosarcoma,
cases (1.25%, all with cardiac fibroma). and one malignant fibrous histiocytoma), the
right ventricle in two (one leiomyosarcoma, one
malignant fibrous histiocytoma), the pulmonary
Primary Malignant Bioptic Cardiac artery in two (leiomyosarcoma), and the pericar-
Tumors dium in four (malignant mesothelioma in three
and undifferentiated sarcoma in one); finally, in
The population consists of 26 patients, 15 male two lymphomas cardiac involvement was diffuse
and 11 female, age ranging 21–80 years, mean without any chamber predilection.
50 ± 13. They died within 6 months from clinical
onset, with the exception of three cases, i.e., a
21-year-old woman with left atrial leiomyo- Primary Benign Bioptic Cardiac
sarcoma, who was still alive 96 months after sur- Tumors
gical resection and adjuvant chemotherapy [10];
and two cases operated of right atrial angiosar- A consecutive series of 213 bioptic benign car-
coma who were alive at a follow-up of 12 and 18 diac tumors have been studied in the same years,
months, respectively. The most prevalent histo- mean 48.1 ± 22.5, median 53 years. Figure 2.4
type was leiomyosarcoma and angiosarcoma illustrates the various histotypes.
(19% each) and undifferentiated sarcoma Cardiac myxoma is the most frequent primary
cardiac tumor. A consecutive series of 141 surgi-
Malignant
schwannoma
Fibrosarcoma
Lymphoma
Mesothelioma
Malignant fibrous
histiocytoma
Undifferentiated
sarcoma
Angiosarcoma
Leiomyosarcoma
0 1 2 3 4 5 6
Fig. 2.3 Primary bioptic malignant cardiac and pericardial tumors, University of Padua Medical School (1970–2010):
26 cases. Prevalence of various tumor histotypes
Cystic tumor of the atrioventricular node
Rhabdomyoma
Teratoma
Hematic cyst
Lipoma
Fibroma
Hemangioma
Pericardial cyst
Papillary fibroelastoma
Myxoma
0 20 40 60 80 100
Fig. 2.4 Primary bioptic benign cardiac and pericardial tumors, University of Padua Medical School (1970–2010): 213
cases. Prevalence of various tumor histotypes
45
40
35
30
N. cases
25
20
15
10
0
0-10 yrs 11-20 yrs 21-30 yrs 31-40 yrs 41-50 yrs 51-60 yrs 61-70 yrs >70 yrs
Fig. 2.5 Cardiac myxoma, University of Padua Medical School (1970–2010): 141 bioptic cases. Distribution accord-
ing to age intervals
cally resected myxomas has been collected, repre- Location of cardiac myxoma was mostly the
senting 59% of all primary bioptic cardiac tumors left atrium (116 cases, 82.5%), followed by the
and 66% of benign bioptic cardiac tumors. The right atrium (22 cases, 15.5%), and exceptionally
majority were female (88, 62.5%), the age range the ventricles (the right ventricle in two cases and
was 2–85 years (mean 54 ± 16, median 56). the left ventricle in one case, 2%) (Fig. 2.6). In
Figure 2.5 reports the distribution of cardiac myx- our experience, a valvular location was never
omas per age, showing a peak of incidence in people observed. The weight ranged from 2 to 125 g
50–60 years of age; only six cases (4%) have been (mean 38 ± 24) and the surface was smooth in
surgically resected in the pediatric age (<18 years). 65% and villous in 35% of cases.
28 G. Thiene et al.
RA
RV LV
15.5%
LA
82.5%
Fig. 2.6 Cardiac myxoma, University of Padua Medical

School (1970–2010): 141 bioptic cases. Distribution
according to tumor location (LA left atrium; LV left ven-
tricle; RA right atrium; RV right ventricle) Fig. 2.8 Papillary fibroelastoma, University of Padua
Medical School (1970–2010): 20 bioptic cases. Distribution
according to tumor location (AV aortic valve, LA left
As far as clinical presentation is concerned, atrium, LV left ventricle, MV mitral valve, PV pulmonary
valve, TV tricuspid valve)
signs and symptoms of hemodynamic obstruction
were present in 60% of cases, constitutional
symptoms in 30%, embolic phenomena in 16%, patients, the diagnosis was incidental during rou-
while one-fourth of patients were asymptomatic tine echocardiograpy (seven) or during cardiac sur-
and myxoma was an incidental finding during gery (three), while in the remaining nine patients it
echocardiographic examination (Fig. 2.7). was achieved due to signs and symptoms of myo-
cardial ischemia (six cases), heart failure (two
Papillary fibroelastoma (or endocardial papilloma)
cases) or arrhythmias (one case).
represents the second most frequent primary car-
diac tumor after myxoma. Twenty cases have been Hemangioma. Ten patients were studied, 4 males,
surgically resected in 19 patients (8.5% of all pri- age ranging from 2 days to 73 years, mean 30 ± 30
mary bioptic cardiac tumors and 9.5% of benign years, median 19 years. Cardiac hemangioma
bioptic cardiac tumors), 11 female, age ranging was intramural in 2 (left ventricular free wall and
24–78 years, mean 57 ± 17, median 52.5 years. The atrial septum, one each), intracavitary in 7 (right
location was the valvular endocardium in 16 (aortic atrium in 2, right ventricle in 2, left atrium in 1,
valve in 6, mitral valve in 5, tricuspid valve in 4, left ventricle in 1, mitral valve in 1), and pericar-
and pulmonary valve in 1) and the mural endocardial in 1. The diagnosis was achieved during
dium in 4 (left ventricular cavity and/or papillary echocardiographic examination (nine cases) or
muscles in 2 and left atrial cavity in 2) (Fig. 2.8). In 10 intraoperatively (one case).
Fig. 2.7 Cardiac myxoma, University of Padua Medical School (1970–2010): 141 bioptic cases. Clinical presentation
Fibroma. Seven patients, four female, age ranging Lipoma. Five surgically resected cases have been
1 month–40 years (mean 6 ± 14 years, median 6 studied, including a 75 year old woman with
months) were studied. The fibroma was located lipomatous hypertrophy of the interatrial septum.
in the interventricular septum in three, right ven- The remaining four cases are true lipomas, with
tricular free wall in two, and left ventricular free either an intracavitary growth (on the mitral
wall in two. In three cases, surgical resection was not valve-male 24 year old—and in the right atrium—
feasible and cardiac transplantation was performed. male 61year old and female 85 year old) or peri-
cardial (male 64 year old).
Hematic cyst. Four cases were collected, all in
infants (two male and one female, age ranging Cystic tumor of the atrioventricular node (or
4–11 months) but one (a 70-year-old woman). Tawarioma). One surgically resected case has
Two of them occurred in the setting of a congenital been examined in a full heart specimen coming
heart disease (hypoplastic right heart and tetralogy from cardiectomy for heart transplantation
of Fallot, respectively). They were located at the (male 39 year old, dilated cardiomyopathy).
level of the tricuspid valve in two, of the right atrium
Pericardial cyst. Thirteen cases, 10 male and three
in one, and of inferior vena cava orifice in one.
female, age ranging 22–68 years, mean 48.5 ± 13,
Teratoma. Four patients, one male and three median 52 years have been collected. These tumors
female, age ranging 1 month–35 years (median 1 represent the third most common primary cardiac
month) were operated, all but one presenting with and pericardial tumor in our bioptic experience,
congestive heart failure since birth and with radio- after myxoma and papilloma.
graphic and echocardiographic evidence of peri-
cardial mass.
Rhabdomyoma. Six patients, three female and
Primary Cardiac Tumors in the
three male, age ranging 7 days–4 months (mean
Pediatric Age (<18 years)
46 ± 47 days, median 22 days), had a surgically
resected rhabdomyoma. In all, cardiac rhab-
The pediatric experience (<18 years) consists of
domyoma had an intracavitary growth with
29 cases (12% of all primary bioptic cardiac
obstructive symptoms, at the level of the left ven-
tumors), 13 female and 16 male, age ranging 1
tricular outflow tract in four and of the right ven-
day–18 years, mean 43 months, median 4 months.
tricular outflow tract in two.
Fig. 2.9 Primary cardiac tumors in the pediatric age, University of Padua Medical School (1970–2010): 29 bioptic
cases (12%). Prevalence of various tumor histotypes
30 G. Thiene et al.
They are all benign primary cardiac tumors, diseases for oncology. 3rd ed. Geneva: World Health
consisting of 6 myxomas (21%), 6 fibromas Organization; 2000.
6. Fletcher CDM, Unni KK, Mertens F. World Health
(21%), 6 rhabdomyomas (21%), 5 hemangiomas Organization classification of tumours. Pathology and
(17%), 3 pericardial teratomas (10%), and 3 genetics of tumours of soft tissue and bone. Lyon:
hematic cysts (10%) (Fig. 2.9). IARC Press; 2002.
7. van Unnik JA, Coindre JM, Contesso C, Albus-
Lutter CE, Schiodt T, Sylvester R, Thomas D,
Bramwell V, Mouridsen HT. Grading of soft tissue
References sarcomas: experience of the EORTC soft tissue
and bone sarcoma group. Eur J Cancer.
1. Lam KY, Dickens P, Chan AC. Tumors of the heart. A 1993;29:2089–93.
20-year experience with a review of 12,485 consecutive 8. Trojani M, Contesso G, Coindre JM, Rodesse J, Bui
autopsies. Arch Pathol Lab Med. 1993;117:1027–31. NB, de Mascarel A, Goussot JF, David M, Bonichon
2. Wold LE, Lie JT. Cardiac myxomas: a clinicopatho- F, Lagarde C. Soft-tissue sarcomas of adults: study of
logic profile. Am J Pathol. 1980;101:219–40. pathological prognostic variables and definition of a
3. Terribile V, Fassina A. Le neoplasie secondarie del histopathological grading system. Int J Cancer.
cuore. In: Il problema delle metastasi. Atti del XIV 1984;33:37–42.
Congresso Nazionale della Società Italiana di 9. Burke AP, Virmani R. Tumours of the heart and great
Patologia (Catania, 3–6 novembre 1977). Roma: vessels. 3rd ed. Washington, DC: Armed Forces
Società Editrice Universo, 1978. p. 426–31 Institute of Pathology; 1996.
4. Travis WD, Brambilla E, Muller-Hermelink H, Harris 10. Mazzola A, Spano JP, Valente M, Gregoriani R,
CC. Pathology and genetics of tumours of the lung, Villani C, Di Eusanio M, Ciocca M, Minuti U,
pleura, thymus and heart. Lyon: IARC Press; 2004. Giancola R, Basso C, Thiene G. Leiomyosarcoma of
5. Fritz A, Jack A, Parkin DM, Percy C, Shanmugarathan the left atrium mimicking a left atrial myxoma.
S, Sobin L, Whelan S. International classification of J Thorac Cardiovasc Surg. 2006;131:224–6.
Cardiac Myxoma
3
Giovanni Bartoloni and Angela Pucci
relapse following incomplete surgical resection,

Introduction have contributed to the controversial issue of
malignant myxomas or metastatic potential of
Primary cardiac tumors are rare and cardiac myx- cardiac myxomas [17–19]. Several histological,
omas represent the most common neoplasms cytogenetic, and molecular studies have been
among these [1–4]. The mean age at diagnosis is investigating their pathological and biological
50 years, but occasionally they can be seen in characteristics, including mechanisms of growth
younger patients, and they are mainly found in and embolic potential, and increasing evidences
females, localized to foramen ovale in the left are confirming the benign biology of cardiac
atrium and in up to 5% of cases overriding it and myxoma. Modern histological criteria and diag-
apparently looking as a biatrial tumor [5–8]. nostic tools (i.e., immunohistochemistry and
Cardiac myxomas are usually single tumors [4, 6], molecular biology) are helpful for differential
but rarely they can be multiple and familial as diagnosis from myxoid sarcomas that may share
part of Carney complex [9–13]. They have uncer- similar gross features but have malignant behav-
tain histogenesis and show a wide range of clini- ior and often poor prognosis [17, 20].
cal presentations that may mimic a variety of
neoplastic and nonneoplastic conditions [14, 15].
Cardiac myxomas may cause recurrent strokes, Epidemiology
peripheral or pulmonary embolism, and constitu-
tional symptoms (i.e., fever, weight loss, high Primary tumors of the heart are rare, their reported
sedimentation rate, anemia, and/or leucocytosis), incidence ranging between 0.0017 and 0.03% in
syncope, or even sudden death [16]. These tumor autopsy series, and 50% of them are represented
characteristics, together with possible tumor by myxoma [2, 6, 14]. This percentage value
might be underestimated, because in surgical
series they represent up to 78% of primary heart
tumors [1, 4]. They show a female preponder-
G. Bartoloni, M.D. (*) ance, with F/M ratio of 1.8/1, a mean age at diag-
Histopathology Department, “GB Ingrassia” Catania nosis of 50 years, most patients being in 30–60
University, via Santa Sofia, 87, Catania 95123, Italy
age range [5, 17]. Nevertheless they are reported
e-mail: gbartolo@unict.it
also in pediatric age, and as a part of a genetic
A. Pucci, M.D.
disease (i.e., Carney complex) they are diagnosed
Histopathology Department, Azienda Ospedaliera-Pisa
University Hospital, via Roma, Pisa 56126, Italy in young patients without sex predilection
e-mail: angelapucci@libero.it [13, 21, 22].

32 G. Bartoloni and A. Pucci
cutaneous myxoma, and blue naevi) [10] syn-

Clinical Aspects drome and associated with the germline mutation
PRKAR1A [29, 30]. Carney complex has been
The clinical features are determined by their location, firstly described in 1985 by Carney, it represents
size, and mobility, and there is no any pathognomonic about 10% of total cardiac myxoma cases and is
sign or symptom [2, 14, 15]. The most common usually diagnosed in younger patients with no
presenting symptom is systemic embolism (30–50% sex differences [13]. Approximately 30–60% of
of cases) requiring histology for etiological diagno- Carney complex patients will develop cardiac
sis, followed by congestive heart failure because of myxomas and cardiac complications are the cause
mitral valve obstruction with possible supraventricu- of death in more than half of them [31–33].
lar arrhythmias [15]. Atrial myxomas may cause The most recent diagnostic criteria of Carney
obstruction of (pulmonary or systemic) venous drain- complex include spotty skin pigmentation, cuta-
age or of atrio-ventricular valves with valve stenosis, neous and cardiac myxomas, breast myxomatosis,
syncope, and even sudden death after abrupt mitral paradoxical positive response of urinary gluco-
valve obstruction [16, 23]. corticosteroids to dexamethasone administration
Nonspecific constitutional symptoms and during liddle’s test, acromegaly, blue nevus and
signs may occur in up to 90% of cases. They epithelioid blue nevus, osteochondromyxoma
include myalgia, muscle weakness, arthralgia, and/or thyroid carcinoma [12, 29, 34, 35].
fever, weight loss, fatigue, and skin manifesta-
tions, and may be associated with elevated serum
levels of inflammatory cytokines (in particular Tumor Biology
IL-6) [24, 25]. Such signs and symptoms do
occur in a variety of other infectious (endocardi- The growth speed of cardiac myxoma is esti-
tis or rheumatic fever), or immunologic (rheuma- mated to be quite low, about 0.15 cm per month
toid arthritis, vasculitis, connective tissue) or 1.8 cm per year, corresponding to a monthly
diseases but also in other neoplastic conditions weight increase of 1.2 g or 14 g per year, but
(often associated with malignant tumors). recent echocardiographic data have raised the
Unusual clinical presentations have been issue of a possible higher growth rate [36, 37].
described in a few cases of cardiac myxomas, On the other hand, growth may be influenced by
including infected cardiac myxomas that are very the possible overlapping of various phenomena
fragile and may lead to a catastrophic disorder such as thrombosis, hemorrhage, or fragmenta-
with systemic bacteremia, mycotic embolism, tion causing tumor detachment and embolism.
and disseminated intravascular coagulation [26] Metalloproteases (MMP)-2 and MMP-9 over-
or anecdotical cases with pulsatile tinnitus, back expression has been found in embolic cardiac
pain, and hair loss [27]. myxomas; it might increase the risk of embolism
In a minority of cases, cardiac myxomas are by contributing to excessive degradation of tumor
asymptomatic representing an incidental finding extracellular matrix [38].
at autopsy or in vivo, this latter event being quite Mucins are expressed within myxoma matrix
frequent nowadays because of the widespread and their presence could favor tumor embolism
use of echocardiography in routinely diagnostic [39]. In particular, expression of membrane-associ-
investigations [14]. ated MUC1 has been reported to be higher than that
Multiple cardiac myxomas are rare [6, 14]. of the secreted mucins, MUC2 and MUC5AC, the
They may be localized to the ventricles, show a latter one having been related to lesser embolism.
high recurrence rate and be part of Carney com- Increased IL-6 and/or a1-globulin serum lev-
plex, a familial disorder with autosomical domi- els can be found in patients with cardiac myxoma,
nant transmission including NAME (naevi, atrial and have been proposed as predictive markers of
myxoma, myxoid neurofibromata, and ephelides) embolic accidents; they represent activated
[28] or LAMB (lentigines, atrial myxoma, muco- immunological phenomena influencing tumor
3 Cardiac Myxoma 33
remodeling and increasing embolic potential [24, in vitro cell cultures comparing thrombus and
25]. Moreover, a correlation has been seen cardiac myxomas [50–52].
between the preoperative tumor size (i.e., maxi-
Thrombotic theory. Development of cardiac myx-
mum diameter) and IL-6 and/or a1-globulin lev-
omas from thrombus has been hypothesized [53].
els (P < 0.005) [25].
Myxomas apparently have a slow growth rate as
Recently, plakophilin-2 has been identified as a
mural intracardiac thrombus, often are partially
major protein of adherens junctions in cardiac
covered by thrombotic depositions (similar to
myxomas [40]. So far, this type of junction has
Lambl excrescences at gross examination) and
only sporadically been noted in some isolated cells
share common features with organized thrombus
or cell groups in a rhabdomyosarcoma, and gen-
(i.e., mucoid deposits, possible cartilaginous and/
eral occurrence of plakophilin-2, associated with
or osseous metaplasia) [54]. But cardiac myxomas
cadherin-11 in myxoma adherens junctions dis-
are characterized by the typical neoplastic lepidic
closes new clues as to cell–cell adhesion and tumor
cells and by a well-defined vascularization.
growth and to new possible therapeutic concepts.
Dysembryoplastic theory. Cardiac myxoma has
been supposed to represent a hamartoma origi-
Histopathogenesis nating from endocardial embryonic myxoid rests
localized to foramen ovale [16]. But, differently
Origin and histopathogenesis of cardiac myxoma from other cardiac hamartomas such as rhab-
are controversial, the two main hypotheses sug- domyomas, they are not present at birth, being
gesting an origin from multipotent mesenchymal usually diagnosed late in life, and do not sponta-
cells or from neural endocardial tissue [1–4, 41–49]. neously regress [7, 8].
Their preferential site (i.e., foramen ovale) is Histopathogenesis of glandular cells in myxoma.
considered to be consistent with an origin from Glandular structures may be rarely found within an
multipotent mesenchymal cells or from embry- otherwise typical cardiac myxoma. Morphological
onic rests [42, 43]. Kodama et al. have shown the and immunohistochemical studies support two his-
expression of gene transcript in myxoma cells topathogenetic hypotheses, that is a possible origin
compatible with a mesenchymal origin [45]. Other from embryonic foregut rests [46, 55] or a progres-
authors have shown differentiation patterns and sive differentiation from neoplastic multipotent
gene expression compatible with an origin form myxoma cells [17]. During the embryonic develop-
endocardial neural or embryonic tissue [44, 49]. ment, the foregut and the primitive heart tube lie
Moreover, cardiac myxomas show peculiar features adjacent and in the same area as most cardiac myx-
as compared to their extracardiac counterpart omas, i.e., the foramen ovale, therefore glandular
[20]. They share a similar mucopolysaccharide- foregut rests might result to be embedded within
rich extracellular matrix, but extracardiac myxo- myxoma, although embryonic glandular structures
mas lack the typical vascular and syncytial-like have never been described in the interatrial septum
pattern of cardiac myxomas. so far. Finally, lack of other cell lines and the differ-
Neoplastic theory. Cardiac myxoma is consid- ent localization of myxomas are not consistent with
ered an actual neoplasm. It is histologically teratoma hypothesis.
distinct from thrombus that may echocardio-
graphically and grossly mimic cardiac myxoma.
Many evidences are supporting the neoplastic Genetics
hypothesis, either by showing a definite pattern
of differentiation, on the basis of cytological, PRKAR1A gene mutations in chromosome 2,
ultrastructural, and immunohistochemical fea- band p16 and in chromosome 17, bands q22–24
tures, or demonstrating the biological character- are found in cardiac myxomas associated with
istics by using experimental models such as Carney complex [29, 56], whereas most sporadic,
non-familial myxomas do not show mutations

[57]. Casey et al. demonstrated that mutations of Gross Features
PRKAR1A gene, codifying the regulatory sub-
unit R1a of protein kinase A c-AMP dependent, Myxomas are intracardiac tumors and are more
acting as a tumor suppressor gene, are responsi- frequently found in the left atrium (about 75% of
ble of Carney complex [31, 34]. The Carney the cases), localized to the interatrial septum and
complex gene 1 was identified 10 years ago as the adjacent to foramen ovale, although they may be
regulatory subunit 1A of protein kinase A found in any other cardiac chamber, i.e., right
(PRKAR1A) located at 17q22–24 [30, 31]. An atrium (15–29%) or ventricles, whereas they are
inactivating heterozygous germline mutation of rare on a cardiac valves [1–4]. In this latter case,
PRKAR1A is observed in about two-thirds of for a correct differential diagnosis, it has to be
Carney complex patients [31–33]. Such muta- excluded the most frequent valve tumor, i.e., pap-
tions cause haploinsufficiency and reduction of illary fibroelastoma that may show gross features
protein with predisposition to tumorigenesis. similar to myxoma, or the rare myxoid
As to DNA analysis, many sporadic cases of fibrosarcoma of the heart [2].
cardiac myxomas have been shown to be diploid Cardiac myxomas have a highly variable
[58, 59]. size, in most cases the maximum diameter is
Fig. 3.1 Gross features of cardiac myxomas. (a) Myxoma same tumor evidencing attachment base, hemorrhagic
with villous features, showing friable and soft projections foci, myxoid aspects, and a well-defined, necrotic area
on the surface. (b) Polypoid, oval myxoma with smooth just beneath the tumor surface (asterisks). (d) Lobulated
and lobulated surface. Tumor attachment on the interatrial myxoma external surface; dark hemorrhagic foci are
septum has been resected (arrow). (c) Cross-section of the intermingled with pale yellow myxoid areas
3 Cardiac Myxoma 35
between 6 and 7 cm with a mean weight of 40 g. tures and numerous thin-walled blood vessels are
Myxoma often presents as a smooth, oval and found together with the characteristic myxoma
lobulated, or villous, friable and soft or gelati- cells, or lepidic cells [2, 4, 17] (Fig. 3.2) indicat-
nous-like mass (Fig. 3.1). Flat and sessile myx- ing (see ancient Greek lepis term) the scale-like
omas are rare, and might result from embolization cell shape. Lepidic cells are stretched or star-
of most tumor mass. Rarely, cardiac myxomas shaped, show round or oval nucleus with often
show extensive calcifications with stone-like evident nucleolus, may be binucleated and even
consistency, the so-called lithomyxoma [60], display syncytial features, but they lack mitotic
which is usually asymptomatic although com- figures. They can be single, scattered cells or
plete embolization has been reported after pedi- more frequently, they constitute small nests,
cle detachment with floatation into the aorta cord-like or perivascular structures. Perivascular
causing patient death [61]. structures are made up of single or multiple lep-
idic cell layer/s surrounding a central lumen with
endothelial lining, with alcian-blue amorphous
Histology substance deposits between the lepidic cell lay-
ers. Associated features consist of hemorrhage,
Common features. Cardiac myxoma is largely extramedullary hematopoiesis, inflammatory
made up by amorphous mucopolysaccharide-rich infiltrates (made up of granulocytes, lympho-
matrix conferring the typically myxoid aspect. cytes, plasma cells, macrophages, and hemosid-
Within the myxoid stroma, few fibrillary struc- erin-laden macrophages), hemosiderin deposits,
Fig. 3.2 Histologic features of cardiac myxomas. (a, b) Hemosiderin deposits and hemorrhage are also present.
Myxoma (lepidic) cells are embedded within myxoid (c) Myxoma cells with syncytial-like features.
stroma, as scattered single cells (asterisk), small solid (d) Extracellular deposits of hemosiderin with stretched
nests (arrow) or in layers around vessels (double asterisk). structure (bamboo-shaped pattern)
Fig. 3.3 Glandular myxomass .Reprinted with permis- (d) carcynoembryonic antigen (CEA), (e) protein S100,
sion of the Italian Society of Cardiology. (a) Glands are (f) neuron-specific enolase (NSE), cytokeratins 7 (g) and
present at the base of a myxoma. (b) High power view 20 (h) or (i) chromogranin A. Hematoxylin and eosin (a,
of glandular epithelium. Immunoreactivity of glandu- b) avidin–biotin complex, hematoxylin counterstaining
lar epithelium for (c) pan-cytokeratin (AE1/AE3), (c–i)
dystrophic calcifications (with possible Ghandi- cardiac myocytes and also in the medial arteriolar
Gamna sclerosiderotic areas and granulation tis- wall of the peduncle vessels. Then, wide excision
sue) and/or metaplastic ossification together with margins of myxoma basis is required for prevent-
limited foci of necrosis [62]. Calcifications may ing tumor recurrence.
develop also within cell cords or pseudovascular
cuffings, with characteristic stripe or ring shapes, Glandular cardiac myxoma. At least 28 cases of
both of them showing faded edges. Finally, the sporadic or familiar myxomas with glandular
extracellular deposits of hemosiderin may structures have been reported so far [50, 55,
develop a stretched structure, i.e., the so-called 63–65]. Glandular cardiac myxoma has the same
bamboo-shaped pattern. biological and clinical behavior as non-glandular
The myxoma pedicle is mainly constituted by myxoma [9, 17, 55], but epithelial cells may
fibrous tissue with thick-walled vessels, includ- display atypia [55, 63] causing troublesome
ing arterioles with possible medial and/or intimal differential diagnosis from adenocarcinoma
hyperplasia. At tumor basis, myxoma may micro- metastasis [64] (Fig. 3.3). As to the rarely reported
scopically infiltrate the adjacent endocardium malignant glandular myxomas [66–69], in most
and the underlying myocardium. Histologically, cases the malignant behavior appears to be
the infiltration is characterized by a stromal myx- actually dependent upon embolism, local recur-
oid intercellular substance, which together with rence, or multifocality of tumor associated with
rare lepidic cells, makes its way through the incomplete excision [43, 70]. The glands are
3 Cardiac Myxoma 37
Fig. 3.3 (continued)
mainly localized close to tumor base, either or elongated glands usually centrally located in
scattered in a loose myxoid stroma or within myxoma cell islands. Chronic inflammatory
myxoma cell islands. In the former pattern, single infiltrates may be present, around the glands or as
glandular structures or glandular clusters are intraepithelial granulocytes similar to active
found in the loose myxoid stroma, adjacent to the inflammation of the gastrointestinal mucosa.
classical polygonal cell clusters of cardiac myxo- We have observed three cases of glandular myx-
mas. The latter pattern is characterized by round oma, including a case with mild cellular atypia,
Fig. 3.4 Other immunohistochemical features of cardiac antigen immunoreactivity is shown in the inner endothe-
myxomas (a) S100-immunoreactivity is shown in lepidic lial cells (arrow) and in few myxoma cells (asterisk).
myxoma cells whereas the inner endothelial cell layer (d) alpha-actin immunoreactivity in a group of smooth
(asterisk) is negative. (b) Calretinin-immunoreactivity muscle cells (arrow) adjacent to myxoma lepidic
in syncytial-like myxoma cells. (c) CD31 endothelial (asterisk) cells
all of them undergoing complete excision specific enolase), protein S100, and synapto-
without recurrence and free of events at a >5-year physin, but also for vimentin and endothelin-1
follow-up [55]. [17, 43, 44, 50, 72] (Fig. 3.4). Epithelial and
monocyte/macrophage markers are usually nega-
Other unusual features. Calcifications may be
tive. Endothelial markers (FVIII, UEA, CD31,
present in cardiac myxomas and rarely they are
CD34, and UEA-1) are expressed by the endothe-
so extensive to be consistent with lithomyxoma
lium of vessels present within myxoma, includ-
which may require throughout histological exam-
ing the inner endothelial layer of myxoma cell
inations for diagnosis, the typical myxoma fea-
nests, but immunoreactivity has been variably
tures (lepidic cells) being very limited [60, 61].
detected in the lepidic cells [43, 73, 74]. Such
Recently, thymic rests with neoplastic transfor-
immunoreactivity pattern highlights the differen-
mation have been described in two. otherwise
tiation capabilities of lepidic cells and may sup-
typical cardiac myxomas [71].
port the most recent histogenetic hypotheses to
origin from multipotent or embryonic stem cells,
even if it has to be pointed out that neoplastic
Immunohistochemistry
cells might express aberrant histotypes which do
not always correlate to cell origin.
Lepidic cells. Neoplastic cells of myxoma have
been shown to be immunoreactive for Calretinin, Glandular cells. Epithelial glandular cells, rarely
PGP 9.5 (protein gene product), NSE (neuron- present in myxomas, show an epithelial immunore-
3 Cardiac Myxoma 39
Fig. 3.5 Electron microscopy features of cardiac shown in the cytoplasm. Mast cells (M) and collagen
myxomas, lepidic cell of a cardiac myxoma (MC): rough bundles are present within osmiophilic stroma (Uranyl
endoplasmic reticulum, lysosomes, and iron deposits are acetate and lead citrate counterstaining)
activity pattern, i.e., cytokeratines 7 and 20, EMA, pattern. Secretion activity of the myxoma neoplas-
CEA, NSE, S100, and (focally) chromogranin tic cell is in fact expressed in the synthesis of the
positivity that is similar to the fundic mucous neoplastic stroma. The cytoplasm shows abun-
cells of the upper gastrointestinal tract [17, 18, dant smooth and rough endoplasmic reticulum,
50, 55, 65] (Fig. 3.3). free ribosomes, polyribosomes, and lysosomes,
aside from pinocytotic vesicles [75, 76].
Other cell elements. Within tumor, vessels of
Moreover, mitochondria of variable shape and
small and medium size (the latter ones usually
dimension are found, together with numerous
close to the base), and smooth muscle cells, local-
filaments of 85–125 Å diameter, and up to 80 Å
ized to the media of blood vessels or in groups of
periodicity, focally showing myofibril-like
cells interspersed in the myxoid stroma, are vari-
arrangement. Iron deposits are frequently present
ably detected (Fig. 3.4). They display their usual
in these cells.
immunohistochemical differentiation pattern,
being immunoreactive for endothelial (FVIII,
EUA, CD31, and CD34) and muscular (muscle-
Differential Diagnosis
specific actin and a-smooth muscle actin)
and Peculiar Clinical Aspects
markers, respectively [43, 74].
Differential diagnosis of intracardiac myxoid
masses requires histology. Myxoid tumors of the
Electron Microscopy heart may correspond to biologically benign
myxoma, to myxoid sarcomas, or even to cardiac
Lepidic cells show a single, round, or elongated metastasis [70, 77, 78]. The presence of myxoid
nucleus, with or without an evident nucleolus, stroma is not a pathognomonic feature and diag-
and unevenly distributed cytoplasmic organelles nosis of myxoma requires the presence of lepidic
(Fig. 3.5). They are characterized by a secretory cells and the absence of mitosis. Hemorrhage,
40
Table 3.1 Cardiac myxoma: gross and histopathological criteria for differential diagnosis of the main intracardiac myxoid and non-myxoid tumors
Undifferenziated pleomorphic
sarcoma (ex-malignant fibrous
Tumors Myxoma Fibrosarcoma Angiosarcoma histiocytoma) Osteosarcoma
Gross features Occasional infiltration Almost usual infiltration Mural infiltration and Mural infiltration Mural infiltration
of attachment base of implant base intracavitary growth
Histological features
Cellularity Isolated cells with incon- Spindle cells with mild atypia Anastomosed vascular Severe atypia with numerous Atypical cells (spindle
spicuous cellular borders, and variable mitotic figures channels, endothelial pleomorphic and multinucle- shaped, epithelioid, rounded,
mild or no atypia, no mitosis cell pleomorphism, ated cells plasmacytoid, etc.)
frequent mitoses
Architecture Syncytial aggregates cell Fasciculated pattern, frequent Variable and pleomor- Wide storiform arrangement Mild fasciculated arrange-
cords herringbone arrangement phic pattern ment with osteoid foci
Vascular pattern Perivascular structures Plexiform or arborized Anastomosed vascular Hemangiopericytoma-like Preponderant stroma
capillary network channels compared to vascular
component
Immunoreactivity Vimentin, variable endothe- Vimentin, variable neural Endothelial markers Variable (according or not to Osteonectin, osteocalcin
lial or neural markers markers (CD34, CD31) the different subtypes or
cellular differentiation)
Other histological Inflammatory infiltrate with Several (including myxoid) Extravascular Inflammatory infiltrates Cartilagineous and/or fibrous
features hemosiderin histological subtypes erythrocytes tissue
Calcifications, extramedul-
lary hemopoyesis, metaplas-
tic bone
G. Bartoloni and A. Pucci
3 Cardiac Myxoma 41
hemosiderin deposits, and inflammatory cells are fibromyxoid sarcoma, etc. by using the modern
frequently found in myxomas but are not specific. diagnostic criteria (Table 3.1) [1, 18, 20, 70, 77, 78].
Base infiltration may be microscopically observed Then, a relapsing myxoid cardiac tumor has to
in myxomas, whereas in sarcomas and malignant be differentiated from a myxoid sarcoma after
tumors it is often quite extensive and grossly evi- excluding incomplete resection of a myxoma or a
dent [1–4]. multicentric myxoma in the case of Carney
Few reports have raised the controversial complex.
issue whether malignant variants of cardiac
myxomas with metastatic potential do exist
[18, 19, 50, 67–70, 79, 80]. In the most recent Conclusions
and updated soft tissue tumor classifications,
cardiac myxoma is considered and classified as Cardiac myxoma has to be considered a benign
a benign neoplasm [20]. Lack of both marked neoplasm of still controversial histogenesis,
atypias and mitosis, slow growth rate, absent although recent histological and molecular stud-
recurrence after radical excision (except in ies have highlighted a few differentiation aspects.
familial forms, i.e., Carney complex, that are Reported cases of malignant and metastatic myx-
often multicentric) are in favor of benign biol- omas might rather represent misdiagnosed myx-
ogy [1–4, 6]. The metastatic potential of car- oid sarcomas or embolic phenomena of
diac myxomas might rather correspond to biologically benign cardiac myxomas. Finally,
clinical consequences of tumor embolism and modern imaging techniques are fundamental for
depend upon morphology of tumor, soft consis- diagnosis of cardiac masses and histology is man-
tency, thrombotic depositions on the tumor sur- datory for either the definitive diagnosis of car-
face and hemodynamic forces that may cause diac myxoma or the differential diagnosis from
detachment of even conspicuous tumor frag- myxoid imitators.
ments with embolism and even occlusion of
peripheral arteries causing ischemic damage of
organs or tissues [14, 15, 17, 81]. Moreover, References
complete resection of cardiac myxoma is cura-
tive also in embolic cases, whereas in malig- 1. Basso C, Valente M, Poletti A. Surgical pathology of
primary cardiac and pericardial tumors. Eur J
nant tumors, proliferative phenomena cause
Cardiothorac Surg. 1997;12:730–7.
distant metastases without ischemic occur- 2. Burke AP, Virmani R. Atlas of tumor pathology.
rences, and surgical therapy is not curative and Tumors of the heart and great vessels. 3rd series, fas-
is not appropriate in most cases with metastatic cicle 16. Washington, DC: Armed Forces Institute of
Pathology; 1996.
disease.
3. McAllister Jr HA. Primary tumors of the heart and
Cardiac myxoma may also cause mitral valve pericardium. Pathol Annu. 1979;14:335–66.
occlusion with severe clinical consequences such 4. Tazelaar HD, Locke TJ, McGregor CGA. Pathology
as syncope and sudden death, similar to benign of surgically excised primary cardiac tumors. Mayo
Clin Proc. 1992;67:957–65.
meningiomas of central nervous system that may
5. Yoon DH, Roberts W. Sex distribution in cardiac
determine intracranial hypertension and com- myxomas. Am J Cardiol. 2002;90:563–5.
pressive phenomena [14, 15]. 6. Burke A, Jeudy Jr J, Virmani R. Cardiac tumors: an
As other benign tumors of soft tissues, cardiac update. Heart. 2008;94:117–23.
7. Becker AE. Primary heart tumors in the pediatric age
myxomas do not show a correspondent malignant
group: a review of salient pathologic features relevant
counterpart, and myxosarcoma is not a recog- for clinicians. Pediatr Cardiol. 2000;21:317–23.
nized entity in the present classifications of soft 8. Isaacs Jr H. Fetal and neonatal cardiac tumors. Pediatr
tissue tumors [20]. In the past, cases of myxosar- Cardiol. 2004;25:252–73.
9. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go
coma have been reported but today they could
VL. The complex of myxomas, spotty pigmenta-
rather be classified as myxoid rhabdomyosar- tion, and endocrine overactivity. Medicine. 1985;64:
coma, leiomyosarcoma, fibrosarcoma, low-grade 270–83.
10. Rhodes AR, Silverman RA, Harrist TJ, Perez-Atayde tions: case report. J Cardiothorac Surg.
AR. Mucocutaneous lentigines, cardiomucocutane- 2011;6:68–71.
ous myxomas and multiple blue nevi: the “LAMB” 27. Rajab TK, Shekar P, Falk RH. Myxoma, dyspnoea, tin-
syndrome. J Am Acad Dermatol. 1984;10:72–82. nitus, scoliosis, and alopecia. Lancet. 2011;377:1378.
11. Carney JA, Hruska LS, Beauchamp GD, Gordon H. 28. Koopman RJ, Happle R. Autosomal dominant trans-
Dominant inheritance of the complex of myxomas, mission of the NAME syndrome (nevi, atrial myxoma,
spotty pigmentation, and endocrine overactivity. mucinosis of the skin, and endocrine overactivity).
Mayo Clin Proc. 1986;61:165–72. Hum Genet. 1991;86:300–4.
12. Stratakis CA, Carney JA, Lin JP, Papanicolaou DA, 29. Stergiopoulos SG, Stratakis CA. Human neoplasms
Karl M, Kastner DL, Pras E, Chrousos GP. Carney com- associated with Carney complex and germline
plex, a familial multiple neoplasia and lentiginosis syn- PRKAR1A mutations: a protein kinase A disease.
drome. Analysis of 11 kindreds and linkage to the short FEBS Lett. 2003;546:59–64.
arm of chromosome 2. J Clin Invest. 1996;97:699–705. 30. Kirschner LS, Sandrini F, Monbo J, Jing-Ping L,
13. Carney JA. Differences between non-familial and famil- Carney A, Stratakis CS. Genetic heterogeneity and
ial cardiac myxoma. Am J Surg Pathol. 1985;9:53–5. spectrum of the PRKAR1A gene in patients with the
14. Reynen K. Cardiac myxomas. N Engl J Med. Carney complex. Hum Mol Genet. 2000;9:3037–46.
1995;333:1610–7. 31. Casey M, Vaughan CJ, He J, Hatcher CJ, Winter JM,
15. Pinede L, Duhaut P, Loire R. Clinical presentation of Weremowicz S, Montgomery K, Kucherlapati R,
left atrial cardiac myxoma. A series of 112 consecu- Morton CC, Basson CT. Mutations in the protein
tive cases. Medicine. 2001;80:159–72. kinase A R1alpha regulatory subunit cause familial
16. Modi K, Venkatesh P, Agnani S, Rowland T, Reddy P. cardiac myxomas and Carney complex. J Clin Invest.
Sudden death in a patient with left atrial myxoma: 2000;106:R31–8.
report of two cases and review of literature. BJMP. 32. Bertherat J. Carney complex (CNC). Orphanet J Rare
2010;3:311–8. Dis. 2006;1:21.
17. Burke AP, Virmani R. Cardiac myxomas. A clinico- 33. Stratakis CA, Kirschner LS, Carney JA. Clinical and
pathologic study. Am J Clin Pathol. 1993;100:671–80. molecular features of the Carney complex: diagnostic
18. Curschellas E, Toia D, Borner M. Cardiac myxomas: criteria and recommendations for patient evaluation.
immunohistochemical study of benign and malignant J Clin Endocrinol Metab. 2001;86:4041–6.
variants. Virch Arch A Pathol Anat. 1991;418:485–91. 34. Casey M, Mah C, Merliss AD, Kirschner LS, Taymans
19. Altundag MB, Ertas G, Ucer AR, Durmus S, Abanuz SE, Denio AE, Korf B, Irvine AD, Hughes A, Carney
H, Calikoğlu T, Ozbagi K, Demirkasimoglu A, Kaya JA, Stratakis CA, Basson CT. Identification of a novel
B, Bakkal BH, Altundag K. Brain metastasis of car- genetic locus for familial cardiac myxomas and
diac myxoma: case report and review of the literature. Carney complex. Circulation. 1998;98:2560–6.
J Neurooncol. 2005;75:181–4. 35. Carney JA, Ferreiro JA. The epithelioid blue nevus. A
20. Fletcher CDM, Unni KK, Mertens F. WHO Classi- multicentric familial tumor with important associations,
fication of tumors: pathology and genetics of tumours including cardiac myxoma and psammomatous melan-
of soft tissue and bone. Lyon: IARC Press; 2002. otic schwannoma. Am J Surg Pathol. 1996;20:259–72.
21. Padalino MA, Basso C, Milanesi O, Vida VL, Moreolo 36. Malekzadeh S, Roberts WC. Growth rate of left atial
GS, Thiene G, Stellin G. Surgically treated primary myxoma. Am J Cardiol. 1989;64:1075–6.
cardiac tumors in early infancy and childhood. 37. Walpot J, Shivalkar B, Rodrigus I, Pasteuning WH,
J Thorac Cardiovasc Surg. 2005;129:1358–63. Hokken R. Atrial myxomas grow faster than we think.
22. Wu KH, Mo XM, Liu YL. Clinical analysis and surgi- Echocardiography. 2010;27:E128–31.
cal results of cardiac myxoma in pediatric patients. 38. Orlandi A, Ciucci A, Ferlosio A, Pellegrino A, Chiariello
J Surg Oncol. 2009;99:48–50. L, Spagnoli LG. Increased expression and activity of
23. Blondeau P. Primary cardiac tumours-French studies of matrix metalloproteinases characterize embolic cardiac
533 cases. Thorac Cardiovasc Surg. 1990;38:192–5. myxomas. Am J Pathol. 2005;166:1619–28.
24. Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal 39. Chu PH, Jung SM, Yeh TS, Lin HS, Chu JJ. MUC1,
PA, Klein B. Constitutive production of interleukin-6 MUC5AC expressions in cardiac myxoma. Virchows
and immunologic features in cardiac myxomas. Arch. 2005;446:52–5.
Arthritis Rheum. 1990;33:398–402. 40. Rickelt S, Rizzo S, Doerflinger Y, Zentgraf H, Basso
25. Yokomuro H, Yoshihara K, Watanabe Y, Shiono N, C, Gerosa G, Thiene G, Moll R, Franke WW. A novel
Koyama N, Takanashi Y. The variations in the immu- kind of tumor type-characteristic junction: plakophi-
nologic features and interleukin-6 levels for the surgi- lin-2 as a major protein of adherens junctions in car-
cal treatment of cardiac myxomas. Surg Today. diac myxomata. Mod Pathol. 2010;23:1429–37.
2007;37:750–3. 41. Stout AP. Myxoma, the tumor of primitive mesen-
26. Yoshioka D, Takahashi T, Ishizaka T, Higuchin T. chyme. Ann Surg. 1948;127:706–19.
Successful surgical resection of infected left atrial 42. Krikler DM, Rode J, Davies MJ, Woolf N, Moss E.
myxoma in a case complicated with disseminated Atrial myxoma: a tumour in search of its origin. Br
intravascular coagulation and multiple cerebral infarc- Heart J. 1992;67:89–91.
3 Cardiac Myxoma 43
43. Pucci A, Gagliardotto P, Zanini C, Pansini S, di not present in sporadic cardiac myxoma. Int J Mol
Summa M, Mollo F. Histopathologic and clinical Med. 2002;9:59–60.
characterization of cardiac myxoma. Am Heart J. 58. Seidman JD, Berman JJ, Hitchcock CL, Becker RL
2000;140:134–8. Jr, Mergner W, Moore GW, Virmani R, Yetter RA.
44. Terracciano LM, Mhawech P, Suess K, D’Armiento DNA analysis od cardiomyxomas. Hum Pathol.
M, Lehmann FS, Jundt G, Moch H, Sauter G, Mihatsch 1991;22:494–500.
MJ. Calretinin as a marker for cardiac myxoma. 59. Rocco M, Pizzolitto S, Luciani M, Antoci B.
Diagnostic and histogenetic considerations. Am J Quantitative analysis of DNA using flow cytometry
Clin Pathol. 2000;114:754–9. and immunocytochemical findings in 16 cases of car-
45. Kodama H, Hirotani T, Suzuki Y, Ogawa S, Yamazaki diac myxomas. Pathologica. 1991;83:295–300.
K. Cardiomyogenic differentiation in cardiac myxoma 60. Basso C, Valente M, Casarotto D, Thiene G. Cardiac
expressing lineage-specific transcription factor. Am J lithomyxoma. Am J Cardiol. 1997;80:1249–51.
Pathol. 2002;161:381–9. 61. Veroux P, Mignosa C, Veroux M, Bartoloni G, Bonanno
46. Johansson L. Histogenesis of cardiac myxomas: an MG, Tumminelli MG. Acute occlusion of abdominal
immunohistochemical study of 19 cases, including aorta: unusual embolization site for a cardiac tumor
one with glandular structures, and review of the litera- mass. Tumori. 2002;88:417–9.
ture. Arch Pathol Lab Med. 1989;113:735–41. 62. Trotter SE, Shore DF, Olsen EG. Gamma-Gandy nodules
47. Govoni E, Severi B, Cenacchi G, Laschi R, Pileri S, in a cardiac myxoma. Histopathology. 1990;17:270–2.
Rivano MT, Alampi G, Branzi A. Ultrastructural and 63. Abenoza P, Sibley RK. Cardiac myxoma with gland-
immunohistochemical contribution to the histogenesis like structure: an immunohistochemical study. Arch
of human cardiac myxoma. Ultrastruct Pathol. Pathol Lab Med. 1986;110:736–9.
1988;12:221–33. 64. Lindner V, Edah-Tally S, Chafkè N, Onody T,
48. Amano J, Kono T, Wada Y, Zhang T, Koide N, Eisemann B, Walter P. Cardiac myxoma with glandu-
Fujimori M, Ito K. Cardiac myxoma: its origin and lar component: case report and review of the litera-
tumor characteristics. Ann Thorac Cardiovasc Surg. ture. Pathol Res Pract. 1999;195:267–72.
2003;9:215–21. 65. Goldman BI, Frydman C, Harpaz N. Glandular car-
49. Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli diac myxomas: histologic, immunohistochemical and
LG, Gabbiani G. Cardiac myxoma cells exhibit ultrastructural evidence of epithelial differentiation.
embryonic endocardial stem cell features. J Pathol. Cancer. 1987;59:1767–75.
2006;209:231–9. 66. de Morais CF, Falzoni R, Ferreira Alves VA.
50. Deshpande A, Venugopal P, Sampath Kumar A. Myocardial infarct due to a unique atrial myxoma
Phenotypic characterization of cellular components of with epithelial-like cells and systemic metastases.
cardiac myxoma: a light microscopy and immunohis- Arch Pathol Lab Med. 1988;112:185–90.
tochemistry study. Hum Pathol. 1996;27:1056–9. 67. Scarpelli M, Montironi R, Ricciuti R. Cardiac myx-
51. Landon G, Ordonez NG, Guarda LA. Cardiac myxoma with glandular elements metastatic to the brain
oma: an immunohistochemical study using endothe- 12 years after the removal of the original tumor. Clin
lial, histiocytic and smooth muscle cell markers. Arch Neuropathol. 1997;16:190–4.
Pathol Lab Med. 1986;110:116–20. 68. Eckhardt BP, Dommann-Scherrer CC, Stuckmann G,
52. Tanimura A, Kitazono M, Nagayama K, Tanaka S, Zollifoker CL, Wenz KU. Giant cardiac myxoma with
Kosuga K. Cardiac myxoma. Morphologic, his- malignant transformed glandular structures. Eur
tochemical and tissue culture studies. Hum Pathol. Radiol. 2003;13:2099–102.
1988;19:316. 69. Uppin SG, Jambhekar N, Puri A, Kumar R, Agarwal
53. Salyer WR, Salyer DC. The development of cardiac M, Sanghvi D. Bone metastasis of glandular cardiac
myxomas and papillary endocardial lesions from myxoma mimicking a metastatic carcinoma. Skeletal
mural thrombus. Am Heart J. 1975;89:4–17. Radiol. 2011;40:107–11.
54. Waller BF, Grider L, Rohr TM, McLaughlin T, 70. Attum AA, Johnson GS, Masri Z, Girardet R, Lansing
Taliercio CP, Fetters J. Intracardiac thrombi: fre- AM. Malignant clinical behavior of cardiac myxomas
quency, location, etiology, and complications: a mor- and “myxoid imitators”. Ann Thorac Surg.
phologic review, part I. Clin Cardiol. 1995;18:477–9. 1987;44:217–22.
55. Pucci A, Bartoloni G, Tessitore E, Carney JA, Papotti 71. Miller DV, Tazelaar HD, Handy JR, Young DA,
M. Cytokeratin profile and neuroendocrine cells in the Hernandez JC. Thymoma arising within cardiac myx-
glandular component of cardiac myxoma. Virchows oma. Am J Surg Pathol. 2005;29:1208–13.
Arch. 2003;443:618–24. 72. Sakamoto H, Sakamaki T, Sumino H, Sawada Y, Sato
56. Kirschner LS, Carney JA, Pack SD, Taymans SE, H, Sato M, Fujita K, Kanda T,Tamura J, Kurabayashi
Giatzakis C, Cho YS, Cho-Chung YS, Stratakis CA. M. Production of endothelin-1 and big endothelin-1
Mutations of the gene encoding the protein kinase A by human cardiac myxoma cells – Implications for
type I-alpha regulatory subunit in patients with the the origin of myxomas. Circ J. 2004;68:1230–2.
Carney complex. Nat Genet. 2000;26:89–92. 73. Boxer ME. Cardiac myxoma: an immunoperoxidase
57. Fogt F, Zimmerman RL, Hartmann CJ, Brown CA, study of histogenesis. Histopathology. 1984;8:
Narula N. Genetic alterations of Carney complex are 861–72.
74. McComb RD. Heterogeneous expression of factor atrium mimicking a left atrial myxoma. J Thorac
VIII/von Willebrand factor by cardiac myxoma cells. Cardiovasc Surg. 2006;131:224–6.
Am J Surg Pathol. 1984;8:539–44. 79. Read RC, White HJ, Murphy ML, Williams D, Sun CN,
75. Ferrans VJ, Roberts WC. Structural features of car- Flanagan WH. The malignant potentiality of left atrial
diac myxomas. Histology, histochemistry, and elec- myxoma. J Thorac Cardiovasc Surg. 1974;68: 857–68.
tron microscopy. Hum Pathol. 1973;4:111–46. 80. Kusumi T, Minakawa M, Fukui K, Saito S, Ohashi
76. Valente M. Structural profile of cardiac myxoma. M, Sato F, Fukuda I, Kijima H. Cardiac tumor
Appl Pathol. 1983;1:251–63. comprising two components including typical
77. Pucci A, Gagliardotto P, Papandrea C, Di Rosa E, myxoma and atypical hypercellularity suggesting
Morello M, di Summa M, Mollo F. An unusual myx- a malignant change. Cardiovasc Pathol. 2009;
oid leiomyosarcoma of the heart. Arch Pathol Lab 18:369–74.
Med. 1996;120:583–6. 81. Al-Mateen M, Hood M, Trippel D, Insalaco SJ, Otto
78. Mazzola A, Spano JP, Valente M, Gregorini R, Villani RK, Vitikainen KJ. Cerebral embolism from atrial
C, Di Eusanio M, Ciocca M, Minuti U, Giancola R, myxoma in pediatric patients. Pediatrics. 2003;112:
Basso C, Thiene G. Leiomyosarcoma of the left e162–7.
Other Benign Cardiac Tumors
4
Cristina Basso, Tomaso Bottio, Gaetano Thiene,
Marialuisa Valente, and Gino Gerosa
(80–90%), attached to the endocardium, more

Papillary Fibroelastoma often valvular than mural. PFE represents the
(or Papilloma) most common primary tumor of cardiac valves,
with preferential localization on the semilunar
Papillary fibroelastoma (PFE, also known as cusps of the aortic valve (Fig. 4.1), followed by
endocardial fibroelastic papilloma or giant Lambl the atrio-ventricular (AV) valves (Figs. 4.2 and
excrescence) represents the second most frequent 4.3) and the pulmonary valve; more rarely, it has
benign lesion after cardiac myxoma, excluding been reported on a wide variety of other endocar-
pericardial cyst [1, 2]. While in the past it was dial locations, including papillary muscles
mostly an incidental autoptic observation, an (Figs. 4.4 and 4.5), chordae tendineae, and atrial
exponential increase of clinically diagnosed PFEs and ventricular walls [6–10].
occurred in the last 20 years due to the wide- At gross examination, it is generally a soft
spread use of two-dimensional trans-thoracic and mass, white–gray in color, although not infre-
trans-esophageal echocardiography, even in quently some brownish areas due to fresh or
asymptomatic patients [3]. In the Armed Forces organizing thrombus superimposition can be
Institute of Pathology series, 8% of primary car- observed. With its multiple papillary fronds, the
diac tumors are represented by PFEs [4]. PFE resembles a sea-anemone, particularly when
It is a benign endocardial tumor lined by it is immersed under water (Figs. 4.1b, 4.3b, and
endothelial cells. Usually small in size (10– 4.4b), otherwise the fronds can collapse and the
20 mm), some PFE can reach greatest dimensions tree-like structure disappears, thus explaining
(up to 50 mm) [5]. They are mostly single masses why many PFE are grossly mislabeled as valve
myxomas.
At histopathology examination, each frond
branching out from the main stalk consists of a
C. Basso, M.D., Ph.D. (*) • G. Thiene, M.D. single layer of endothelial cells, covering an inter-
• M. Valente, M.D.
mediate myxoid layer rich in proteoglycans and a
Pathological Anatomy, Department of Cardiac,
Thoracic and Vascular Sciences, Azienda Ospedaliera- central avascular core, in which elastic fibers are
University of Padua Medical School, via A. Gabelli, 61, most prominent [4, 5] (Fig. 4.6). Fibroblasts and
Padua 35121, Italy occasional inflammatory cells are visible in the
e-mail: cristina.basso@unipd.it
inner layers. Acute and organizing thrombi may
G. Gerosa, M.D. • T. Bottio, M.D., Ph.D. be found within the fronds, sometimes obscuring
Cardiac Surgery, Department of Cardiac, Thoracic and
the papillary appearance (Fig. 4.2).
Vascular Sciences, Azienda Ospedaliera-University of
Padua Medical School, via N. Giustiniani, 2, At immunohistochemistry, the single layer of
Padua 35128, Italy endothelial cells covering each frond expresses

46 C. Basso et al.
Fig. 4.1 Papillary fibroelastoma of the aortic valve: inci- coronary cusp with a short pedicle is visible. (b) Gross
dental finding during echocardiographic screening in a view of the surgically resected mass resembling a sea
77-year-old asymptomatic woman (from Bottio et al. [7] anemone under water. (c) Panoramic histologic section of
modified). Reprinted with permission of the Italian the resected mass: multiple fronds are branching out from
Society of Cardiology. (a) Trans-oesophageal 2D echocar- a main stalk, each consisting of a central avascular
diography, short axis: a mobile mass attached to the non- fibroelastic axis (elastic Van Gieson stain)
vimentin and CD34, but much less CD31 and PFEs as giant Lambl endocardial excrescences (a
factor VIII, when compared to the normal frequent finding in valvular heart disease),
endothelium [1, 11]. Some spindle cells in the although, the latter occur typically along the line
inner layers may express S100, to support their of closure of semilunar cusps, while PFE can
dendritic origin. occur anywhere on the cusp surface [4–6]. The
Electron microscopy confirms the connective frequent finding of fibrin within the PFE fronds
tissue structure of the central axis, with longitudi- seems in keeping with the thrombotic or iatro-
nally oriented mature collagen and elastic bun- genic origin of the lesion [1, 4, 12].
dles and fibroblasts immersed within the matrix; Because of its small dimensions, not leading
lining endothelial cells appear hyperplastic and to intracavitary obstruction, and of the consis-
rich in pinocytic vesicles [4, 5]. tency of the papillae due to the firm fibroelastic
The real nature of PFE is still a matter of axis, PFE has been frequently an occasional
debate, so that it has been variously described as finding at autopsy and later on at echocardiogra-
neoplasm, hamartoma, organized thrombus, and phy in asymptomatic patients. However, PFE can
iatrogenic lesion; in the latter situation, PFEs are be a source of distal embolism, due to the detach-
usually multiple and located mostly on the non- ment of platelet and fibrin thrombus layered upon
valvular endocardium. Some authors consider the papillary fronds more than to fragmentation
4 Other Benign Cardiac Tumors 47
Fig. 4.2 Papillary fibroelastoma of the mitral valve in a rior mitral valve leaflet (AO aorta, LA left atrium, LV left
74-year-old woman who underwent coronary artery ventricle, LVOT left ventricular outflow tract, RV right
bypass surgery (from Basso et al. [6] modified). Reprinted ventricle). (b) Gross view of the resected mass, showing
with permission of the Italian Society of Cardiology. (a) the irregular surface with variable color. (c) At histology,
Trans-oesophageal 2D echocardiography: a round mass, a fibrin network is visible within the fibroelastic fronds of
5 mm in diameter, is visible on the atrial side of the ante- the tumor (Heidenhain trichrome stain)
Fig. 4.3 Papillary fibroelastoma of the tricuspid valve in view: a 10 × 15 mm mass (F= fibroelastoma) is attached to the
a 40-year-old woman with a history of palpitations and septal leaflet of the tricuspid valve with a short pedicle (arrow)
effort dyspnea (from Scalia et al. [10] modified). Reprinted (AD right atrium; VD right ventricle; VS left ventricle). (b)
with permission of the Italian Society of Cardiology. (a) Gross view of the surgically excised mass: note the short
Trans-thoracic 2D echocardiography, apical four-chamber fronds of the tumor which resembles a cotton flock
48 C. Basso et al.
Fig. 4.4 Papillary fibroelastoma of the papillary muscle phy: a round mass (arrow) appears attached to the anterior
of the mitral valve: incidental finding in a 77-year-old papillary muscle of the mitral valve (AoV aortic valve, LA
woman with chronic atrial fibrillation (from Bottio et al. [9] left atrium, LV left ventricle, MV mitral valve, RV right ven-
modified). Reprinted with permission of the Italian Society tricle). (b) Gross examination of the excised mass reveals
of Cardiology. (a) Trans-oesophageal 2D echocardiogra- the usual papillary shape due to multiple fronds
of the tumor itself [5, 6, 11]. Angina, myocardial raphy (CT) and cardiac magnetic resonance
infarction, sudden death, transient ischemic imaging (MRI) characterization of PFE has been
attacks, and stroke are often reported as first clin- reported, but tumor visualization is challenging
ical manifestations [5, 14–25]. Moreover, PFEs due to its small dimensions and the rapid move-
localized on the valvular endocardium of the aor- ments with cardiac cycles.
tic semilunar cusps adjacent to the coronary ostia
can lead to fatal myocardial ischemia, due to
transient tumor wedging into the coronary ostium Hemangioma (or Angioma)
itself [13].
Nowadays, PFE is a frequent incidental obser- It is a benign vascular tumor which accounts
vation at echocardiography performed for routine for up to 4% of primary cardiac tumors in the
check-up even in asymptomatic patients. The AFIP series [3] . According to the histopatho-
potential risk of systemic embolism suggests pro- logic features, three patterns can be identi fi ed:
phylactic surgery for left-sided PFEs, with the (a) cavernous hemangioma (multiple dilated
majority of patients undergoing tumor excision thin walled vessels); (b) capillary heman-
without the need for valve replacement. On the gioma (capillary-like smaller vessels); (c)
opposite, the casual finding of right-sided PFEs arterio-venous hemangioma or cirsoid aneu-
does not justify surgery, due to the trivial conse- rysm (dysplastic malformed arteries and
quences of microembolization into the pulmo- veins) [1, 4, 29 ] .
nary circulation [10, 26, 27]. Antiplatelet therapy At gross examination, cardiac hemangiomas
must be considered in any case. show highly variable size, with a maximum diam-
PFE is easily detected by transthoracic two- eter occasionally >8 cm. In about 75% of cases
dimensional echocardiography, usually appear- they present an intramural growth, while in the
ing as a small, mobile, irregular, and pedunculated remaining 25% an intracavitary atrial or ventricu-
valvular mass [28]. It is quite common to observe lar growth is observed (Fig. 4.7). Usually, arterio-
the frond-like shape of the endocardial mass, venous and cavernous hemangiomas are not
with “shimmering” edges, a feature that can help capsulated and tend to be infiltrative intramural,
in differential diagnosis with cardiac myxoma. while capillary hemangiomas are intracavitary to
However, when the fronds are shorter, differen- mimic cardiac myxomas.
tial diagnosis can be difficult thus explaining why The histologic structure is similar to that of
many PFEs undergo surgery with a wrong diag- extracardiac hemangiomas, with the three pat-
nosis of cardiac myxoma [4]. Computed tomog- terns mentioned above (Fig. 4.7d). The capillary
Fig. 4.5 Papillary fibroelastoma of the mitral valve pap- 17 × 15 mm in size, is attached to the anterior papillary
illary muscle in a 31-year-old man with acute myocardial muscle of the mitral valve (LV left ventricle, RV right ven-
infarction and normal coronary arteries (from Valente tricle). (b) Gross view of the resected mass: note the short
et al. [5] modified). Reprinted with permission of the Italian pedicle and the apparently smooth surface out of the
Society of Cardiology. (a) Transthoracic 2D echocardiog- water. (c) Histologic examination reveals the papillary
raphy, apical four-chamber view: a round mass (arrow), structure of the tumor (Heidenhain trichrome stain)
pattern usually presents a myxoid matrix with capillary or venous vascular spaces with either
immersed nodules of small capillary-size vessels, thick or thin walls, full of blood; the arterio-
with endothelial cells, pericytes, and fibroblasts; venous pattern is characterized by heterogeneous
the cavernous pattern consists of large dilated dysplastic vessel types, with muscularized
50 C. Basso et al.
Fig. 4.6 Histologic and ultrastructural features of endocar- (elastic Van Gieson stain). (b) At immunohistochemistry, the
dial papillary fibroelastoma (same case as Fig. 4.5). Reprinted lining cells express endothelial markers (CD31). (c) Scanning
with permission of the Italian Society of Cardiology. (a) Each electron microscopy confirms the papillary structure of the
papillary frond consists of a central fibroelastic core and a tumor. (d) At higher magnification, the continuous endothe-
myxoid matrix, covered by a single layer of endothelial cells lial lining of the papillae is visible
arteries, veins, and capillaries showing irregularly Cardiac hemangiomas can arise from the
thickened walls, and may contain fibrous tissue epicardium and myocardium but are also found
and fat. Cardiac hemangiomas have frequently in cardiac cavities. The most frequent locations
combined features of cavernous, capillary, and are the left ventricular wall, the interventricular
arterio-venous hemangiomas. septum, the right ventricle, and the atria. They are
Papillary hyperplasia of endothelial cells is an rare on the epicardium and even exceptional on
unusual finding, probably due to exuberant reac- the valves [2, 4, 29–33].
tive endothelial proliferation as a part of a pro- From the clinical view point, intracavitary
cess of organizing thrombosis. However, at hemangiomas can present with obstructive symp-
difference from angiosarcoma, necrosis and toms like myxomas, while the intramural ones with
nuclear atypia are never observed. arrhythmias and conduction disturbances, conges-
At immunohistochemistry, the cells lining the tive heart failure, myocardial ischemia, pericardial
vascular spaces typically express endothelial effusion, and exceptionally with cardiac tampon-
markers CD31, CD34, and factor VIII. ade due to intrapericardial rupture. Most cardiac
Fig. 4.7 Right atrial hemangioma in a 62-year-old coronary angiography confirms that the mass is vascular-
woman with effort dyspnea (from Rizzoli et al. [31] ized from a collateral branch of the right coronary artery.
modified). Reprinted with permission of the Italian Society (c) At histology, the mass consists of numerous vascular
of Cardiology. (a) Trans-oesophageal 2D echocardiogra- structures full of blood and lined by a single layer of
phy showing an atrial septal mass protruding into the atrial endothelial cells (Heidenhain trichrome stain). (d) At
cavity to interfere with the blood flow: Color Doppler immunohistochemistry, the lining cells are positive for
reveals an afferent coronary artery branch. (b) Selective endothelial markers (CD31)
hemangiomas are discovered incidentally at through echocardiography and MRI, and of

autopsy or during echocardiographic screening. vascularization of the mass by a coronary artery
The majority of cardiac hemangiomas are branch at angiography or perfusion MRI
sporadic. However, although rarely, an associa- (Fig. 4.7b) [31].
tion with extracardiac hemangiomas of the gas- Among benign vascular tumors, cardiac lymp-
trointestinal tract and port-wine stain of the face hangiomas need to be mentioned. They are usu-
has been reported. The Kasabach–Merritt vascu- ally intrapericardial, although some cardiac
lar syndrome has been described in the setting of variants have been reported [4]. They are soft,
giant cardiac hemangioma, due to thrombosis spongy masses, with solid fibrotic areas, and a
and coagulopathies [34, 35]. histologic structure similar to that of heman-
Diagnosis during life can be suspected on the giomas, where the vascular spaces are filled with
basis of tissue characterization of the mass lymph instead of blood.
52 C. Basso et al.
Lipoma
It is a primary benign cardiac tumor composed

of mature adipocytes [4]. Lipomas usually do
not represent an indication to surgical resec-
tion, thus explaining why their prevalence in
surgical pathology series is low. Higher esti-
mates up to 10% of heart tumors are reported
when lipomatous hypertrophy of the atrial
septum, which is a separate entity, is included
[1, 4, 36–38].
Cardiac lipomas may occur anywhere in the
heart, with a predilection for visceral and parietal
pericardium [2, 4, 39]. Other sites are represented
by interventricular septum and valves (valve
“fibrolipoma”) [40].
Histopathologic examination reveals circum-
scribed masses of mature adipocytes, enmeshed
in a thin fibrous collagen network (Fig. 4.8).
As for other primary cardiac tumors, clinical
presentation is variable depending on the site and
size of lipoma, and many are incidental findings
at autopsy or during cardiac imaging investiga-
tion. CT and MRI can help in the diagnostic
work-up, being able to establish the fatty nature
of the mass.
Lipomas should not be confused with
lipomatous hypertrophy of the interatrial sep-
tum, a non-encapsulated benign lesion charac-
terized by mature adipose cell hyperplasia
intermixed with enlarged cardiac myocytes
typically located in the atrial septum (Fig. 4.9).
A prevalence of 1.1% has been reported in an
autoptic series [36]. It is often associated with
obesity (about one-third of cases), advanced
age, and cardiomegaly, as an intracardiac Fig. 4.8 Right atrial lipoma, incidental finding at
extension of the subepicardial fat, so that echocardiography in a 85-year-old woman followed up
for ischemic heart disease. Reprinted with permission of
lipomatous hypertrophy has been considered
the Italian Society of Cardiology. (a) Gross view of the
an acquired dysmetabolic process; however, surgically resected mass: note the yellow appearance of
its finding also in nonobese people is in keep- the smooth, round intracavitary mass. (b) At histology,
ing with a hamartomatous origin [36–38]. mature adipocytes with interspersed connective tissue are
visible (Masson trichrome stain)
Palpitations due to atrial arrhythmias (atrial
fibrillation or flutter, premature beats) are the
usual clinical symptoms. Conduction distur-
bances may also occur. When the lipomatous may appear to require surgical resection. This
hypertrophy is so large as to interfere or obstruct nosologic entity has been re-emphasized in the clin-
the venae cavae orifices, congestive heart failure ical setting after the advent of cardiac imaging
Fig. 4.9 Lipomatous hypertrophy of the atrial septum epicardial fat. (b) After longitudinal section of the heart,
(atrial septal lipoma) at autopsy in a 74-year-old woman an oval-shaped lipomatous mass, 3 × 2 cm in size, is visi-
with a history of tuberculosis and diabetes (from Basso ble in the atrial septum. (c) At histology, the non-capsu-
et al. [38] modified). Reprinted with permission of the lated mass presents mature adipocytes with tiny interstitial
Italian Society of Cardiology. (a) Ex vivo cardiac magnetic fibrosis and rare cardiac myocytes (Heidenhain trichrome
resonance showing a hyperintense signal similar to that of stain). (d) Close-up of C (Heidenhain trichrome stain)
modalities with tissue characterization properties cusps, in newborns and infants, particularly
such as CT and MRI [41]. under 2 months of age [4, 42]. They consist of
blood entrapped into leaflet crevices, covered
by flat endothelium (Fig. 4.10). They are con-
Blood Cyst (Valvular) sidered like diverticula of malformative ori-
gin, due to the invagination of the valvular
It is a congenital cyst of the valvular endocar- endocardium.
dium, small in size and usually without clinical The sequestered blood may exceptionally
significance. They are usually multiple and increase so much that the cyst, assuming huge
typically located along the closure rim of the intracavitary dimensions, creates obstructive
AV valve leaflets, or more rarely semilunar symptoms and requires surgery [43].
54 C. Basso et al.
Fig. 4.10 Giant blood cyst in a 4 months infant (Gallucci mass which appears dark red. (b) At histology, the cyst
et al. [43]). Reprinted with permission of the Italian Society wall consists of fibrous tissue with rare elastic fibers, cov-
of Cardiology. (a) Gross view of the surgically resected ered by endothelium with clots and mural thrombi
Fig. 4.11 Cystic tumor of the AV node, incidental level of the AV node: note the subendocardial mass con-
finding at autopsy in a 78-year-old woman who died of sisting of multiple cysts variable in size filled with mucoid
ischemic heart disease. Reprinted with permission of the material (Alcian PAS). (b) The cysts are lined by cuboid
Italian Society of Cardiology. (a) Histologic section at the and transitional cells (hematoxylin–eosin stain)
Cystic Tumor of the AV Node ble pericardial dysontogenetic origin). This tumor
is located in the triangle of Koch, at the right side
It is a benign, multicystic mass, also known as of the atrial septum in front of the coronary sinus,
tawarioma (from Tawara, the discoverer of the exactly at the level of the AV node [44–46].
AV node) or celothelioma (mesothelioma of the Tumor histogenesis, whether mesothelial or
AV node, because wrongly considered of possi- endodermal, has been debated for a long time
[1, 4]. Immunohistochemistry studies then provided rarely, they are located in the anterior, superior,
evidence of an origin from “endodermal rem- or inferior mediastinal spaces.
nants” (primitive endoderm), thus abandoning Although most probably congenital, pericar-
the term celothelioma or mesothelioma of the AV dial cysts are usually diagnosed in the adult age,
node. Since the diagnosis can be reached at any without any gender predilection. They are mostly
age, the congenital nature is not proven in all. asymptomatic or pauci-symptomatic, despite the
At gross examination, it appears multicystic huge dimensions they can reach (up to 16 cm)
even at naked eye, ranging in size from 2 to due to increasing storage of fluid within the cys-
20 mm. Histologically, it infiltrates and com- tic cavity. Symptoms include chest pain, dyspnea,
presses the AV node, not touching the borders of cough, palpitations, and even congestive heart
the central fibrous body and without extension failure. Once diagnosed, it does not represent
into the ventricular myocardium or valvular tis- “per se” an indication for surgery, except for
sue (Fig. 4.11). The cysts, which are filled with cases with compressive/obstructive symptoms.
mucoid substance, are lined by cuboid, squamous,
or transitional epithelial cells. At immunohis-
tochemistry, these cells strongly express cytok-
Other Rare Non-myxomatous Benign
eratin, epithelial membrane antigen (EMA),
Cardiac Tumors
carcinoembryonic antigen, and B72.3 [1].
The mean age at presentation is 38 years, with
These are distinct nosologic entities recently
a F/M ratio 3/1. Complete AV block is the clini-
reported as to require an update of the WHO
cal presentation in about 75% of patients, incom-
classification of primary cardiac tumors.
plete AV block in 15%, and sudden death in 10%.
Some are rare incidental findings in newborns Hamartoma of mature cardiac myocytes is a rela-
with congenital heart diseases. tively new entity described in young adults, either
The majority of cases have been diagnosed at asymptomatic or with fatal arrhythmias. It consists of
autopsy or after cardiac transplantation through single or multiple, non encapsulated, poorly demar-
histologic investigation of the conduction system, cated, firm white masses in the ventricles or atria,
although rare cases of in vivo diagnosis with sur- resembling normal myocardium. They are formed
gical removal have been reported [46]. by mature, hypertrophicied cardiomyocytes with
cross striations and large, bizarre nuclei, and spatial
disorganization (“myocardial disarray”) to mimic
Pericardial Cyst focal hypertrophic cardiomyopathy [47].
Adult cellular rhabdomyoma is a quite rare
Pericardial cysts are a frequent incidental finding
benign neoplasm of striated myocytes [48].
during routine chest x-ray. Most probably dison-
Ranging in size from 2 to 5 cm, it presents as soft,
togenetic in nature (i.e., pericardial diverticula),
bulging mass, tan to brown, with a pseudo-cap-
they consist of uni- or multi-loculated cysts, full
sule. At histology, this tumor differs from the
of serous liquid, with a thin and smooth wall.
pediatric cardiac rhabdomyoma since it is com-
At histology, the pericardial cyst wall consists
posed of tightly packed, monomorphic, round to
of highly vascularized connective tissue rich in
polygonal cardiomyocytes with eosinophilic
collagen bundles, with rare elastic fibers and scat-
granular cytoplasm and only occasional spider
tered lymphocytic and plasmacellular infiltrates;
cells. No association with tuberous sclerosis has
the cyst wall is lined on both sides by a single
been reported. The prognosis is unknown but pre-
layer of flat mesothelial cells, sometimes hyper-
sumably benign.
plastic, which express positivity for cytokeratin
[4] (Fig. 4.12). Inflammatory myofibroblastic tumor (also known as
The most common location is the right cardio- plasma cell granuloma or inflammatory pseudotu-
phrenic angle, followed by the left one; more mor) is a very rare cardiac tumor with an
56 C. Basso et al.
Fig. 4.12 Pericardial cyst, incidental finding in a 52-year- with serous fluid. (b) At histology, the cyst wall consists
old man during surgery for mitral valve replacement. of vascularized connective tissue covered by a single layer
Reprinted with permission of the Italian Society of of mesothelial cells (hematoxylin–eosin stain)
Cardiology. (a) Gross view of the uni-loculated cyst filled
endocavitary growth that can be found at any Other benign cardiac neoplasms or tumor-like
endocardial site in the heart, although it prefers the lesions which are not anymore listed in the recent
ventricles. Grossly, they can reach large dimen- WHO classification, but are still mentioned in the
sions (up to 8 cm) and show a relatively narrow series of the Armed Force Institute of Pathology
attachment to the mural endocardium. At histol- and in the literature, include granular cell tumor,
ogy, the mass consists of spindle myofibroblasts, paraganglioma (or cardiac pheochromocytoma),
fibroblasts, and chronic inflammatory cells, such neurofibroma, leiomyoma, intracardiac broncho-
as plasma cells, lymphocytes, macrophages, and genic cyst, thyroid heterotopy, and mesothelial
few eosinophils [1]. Fibrin thrombus deposition on incidental cardiac excrescences (also known as
the surface is a common feature. cardiac MICE) [4].
15. McFadden PM, Lacy JR. Intracardiac papillary

References fibroelastoma: an occult cause of embolic neurologic
deficit. Ann Thorac Surg. 1987;43:667–9.
1. Basso C, Valente M, Poletti A, Casarotto D, Thiene G. 16. Waltenberger J, Thelin S. Papillary fibroelastoma as
Surgical pathology of primary cardiac and pericardial an unusual source of repeated pulmonary embolism.
tumors. Eur J Cardiothorac Surg. 1997;12:730–7. Circulation. 1994;89:24–33.
2. Burke AP, Veinot JP, Loire R, Virmani R, Tazelaar H, 17. Etienne Y, Jobic Y, Houel JF, Barra JA, Boschat J,
Kaniya H, Araoz PA, Watanabe G. Tumours of the Meunier M, Penther P. Papillary fibroelastoma of the
heart. In: Travis WD, Brambilla E, Muller-Hermelink aortic valve with myocardial infarction: echocardio-
HK, Harris CC, editors. Pathology and genetics of graphic diagnosis and surgical excision. Am Heart J.
tumours of the lung, pleura, thymus and heart. IARC 1994;127:443–5.
Press: Lyon; 2004. p. 249–88. 18. Zell DN, Diamond M, Beringer D. Angina and sud-
3. Sun JP, Asher CR, Yang XS, Cheng GG, Scalia GM, den death resulting from papillary fibroelastoma of
Massed AG, Griffin BP, Ratliff NB, Stewart WJ, the aortic valve. Ann Emerg Med. 1985;14:470–3.
Thomas JD. Clinical and echocardiographic charac- 19. Mann J. Papillary fibroelastoma of the mitral valve: a
teristics of papillary fibroelastomas: a retrospective rare cause of transient neurological deficits. Br Heart
and prospective study in 162 patients. Circulation. J. 1994;71:6.
2001;103:2687–93. 20. Fowles RE, Miller DC, Egbert BM, Fitzgerald JW,
4. Burke A, Virmani R. Atlas of tumor pathology. Popp RL. Systemic embolization from a mitral valve
Tumors of the heart and great vessels. Washington, papillary endocardial fibroma detected by two-dimen-
DC: Armed Forces Institute of Pathology; 1996. sional echocardiography. Am Heart J.
5. Valente M, Basso C, Thiene G, Bressan M, Stritoni P, 1981;102:128–30.
Cocco P, Fasoli G. Fibroelastic papilloma: a not so benign 21. Lee KS, Topol EJ, Stewart WJ. Atypical presentation
cardiac tumor. Cardiovasc Pathol. 1992;1:161–6. of papillary fibroelastoma mimicking multiple vegeta-
6. Basso C, Bottio T, Valente M, Bonato R, Casarotto D, tions in suspected subacute bacterial endocarditis. Am
Thiene G. Primary cardiac valve tumours. Heart. Heart J. 1993;125:1443–5.
2003;89:1259–60. 22. Gallo R, Kumar N, Prabhakar G, Awada A, Maalouf
7. Bottio T, Pittarello D, Bonato R, Thiene G, Gerosa G, Y, Duran CM. Papillary fibroelastoma of mitral valve
Casarotto D, Basso C. Echocardiographic diagnosis chordae. Ann Thorac Surg. 1993;55:1576–7.
of aortic valve papillary fibroelastoma. Tex Heart Inst J. 23. Kasarskis EJ, O’Connor W, Earle G. Embolic stroke
2004;31:322–3. from cardiac papillary fibroelastomas. Stroke.
8. Mazzucco A, Bortolotti U, Thiene G, Dan M, Stritoni 1988;19:1171–3.
P, Scutari M, Stellin G. Left ventricular papillary 24. Topol EJ, Biern RO, Reitz BA. Cardiac papillary
fibroelastoma with coronary embolization. Eur J fibroelastoma and stroke: echocardiographic diagno-
Cardiothorac Surg. 1989;3:471–3. sis and guide excision. Am J Cardiol.
9. Bottio T, Basso C, Rizzoli G, Casarotto D, Thiene G. 1986;80:129–32.
Case report: fibroelastoma of the papillary muscle of 25. Fine G, Pai SR. Cardiac papillary fibroelastoma: a
the mitral valve: diagnostic implications and review source of coronary artery emboli and myocardial
of the literature. J Heart Valve Dis. 2002;11:288–91. infarction. Henry Ford Hosp Med J. 1984;32:204–8.
10. Scalia D, Basso C, Rizzoli G, Lupia M, Budano S, 26. Frumin H, O’Donnell L, Kerin NZ, Levine F, Nathan
Thiene G, Venturini A. Should right-sided Jr LE, Klein SP. Two-dimensional echocardiographic
fibroelastomas be operated upon? J Heart Valve Dis. detection and diagnostic features of tricuspid papil-
1997;6:647–50. lary fibroelastoma. J Am Coll Cardiol.
11. Rubin MA, Snell JA, Tazelaar HD, Lack EE, 1983;2:1016–8.
Austenfeld JL, Azumi N. Cardiac papillary 27. Wolfe JT, Finck SJ, Safford RE, Persellin ST.
fibroelastoma: an immunohistochemical investigation Tricuspid valve papillary fibroelastoma: echocardio-
and unusual clinical manifestations. Mod Pathol. graphic characterization. Ann Thorac Surg.
1995;8:402–7. 1991;51:116–8.
12. Boone SA, Campagna M, Walley VM. Lambl’s 28. Shub C, Tajik AJ, Seward JB, Edwards WD, Pruitt
excrescences and papillary fibroelastomas: are they RD, Orszulak TA, Pluth JR. Cardiac papillary
different? Can J Cardiol. 1992;8:372–6. fibroelastomas. Two dimensional echocardiographic
13. Israel DH, Sherman W, Ambrose JA, Sharma S, recognition. Mayo Clin Proc. 1981;56:629–33.
Harpaz N, Robbins M. Dynamic coronary ostial 29. Burke AP, Johns J, Virmani R. Hemangiomas of the
obstruction due to papillary fibroelastoma leading to heart: a clinico-pathologic study of 10 cases. Am J
myocardial ischemia and infarction. Am J Cardiol. Cardiovasc Pathol. 1991;13:283–90.
1991;67:104–5. 30. Brizard C, Latremouille C, Jebara VA, Acar C, Fabiani
14. Basso C, Thiene G, Dalla Volta S. Embolia coronar- JN, Deloche A, Carpentier AF. Cardiac hemangiomas.
ica: una causa spesso dimenticata di infarto mio- Ann Thorac Surg. 1993;56:390–4.
cardico e morte improvvisa. G Ital Cardiol. 31. Rizzoli G, Bottio T, Pittarello D, Napodano M, Thiene
1992;22:751–60. G, Basso C. Atrial septal mass: transesophageal
58 C. Basso et al.
echocardiographic assessment. J Thorac Cardiovasc 40. Benvenuti LA, Mansur AJ, Lopes DO, Assis RVC.
Surg. 2004;128:767–9. Primary lipomatous tumors of the cardiac valves.
32. Chang JS, Young ML, Chiu WM, Lue HC. Infantile South Med J. 1996;89:1018–20.
cardiac hemangioendotelioma. Pediatr Cardiol. 41. Isner JM, Swan 2nd CS, Mikus JP, Carter BL.
1992;13:52–5. Lipomatous hypertrophy of the interatrial septum:
33. Palmer TE, Tresch DD, Bonchek LI. Spontaneous in vivo diagnosis. Circulation. 1982;66:470–3.
resolution of a large, cavernous hemangioma of the 42. Zimmerman KG, Paplanus SH, Dong S, Nagle RB.
heart. Am J Cardiol. 1986;58:184–5. Congenital blood cysts of heart valves. Hum Pathol.
34. Gengenbach S, Ridkler PM. Left ventricular heman- 1983;14:699–703.
gioma in Kasabach–Merritt syndrome. Am Heart J. 43. Gallucci V, Stritoni P, Fasoli G, Thiene G. Giant blood
1991;121:202–3. cyst of tricuspid valve. Successful excision in an
35. Weston CF, Hayward MW, Seymour RM, Stephens infant. Br Heart J. 1976;38:990–2.
RM. Cardiac hemangioma associated with a facial 44. Rossi L, Piffer R, Turolla E, Frigerio B, Coumel P,
port-wine stain and recurrent atrial tachycardia. Eur James TN. Multifocal Purkinje-like tumor of the
Heart J. 1988;9:668–71. heart. Occurrence with other anatomic abnormalities
36. Shirani J, Roberts WC. Clinical, electrocardiographic in the atrioventricular junction of an infant with junc-
and morphologic features of massive fatty deposits tional tachycardia, Lown–Ganong–Levine syndrome,
(“lipomatous hypertrophy”) in the atrial septum. J Am and sudden death. Chest. 1985;87:340–5.
Coll Cardiol. 1993;22:226–38. 45. Nojima Y, Ishibashi-Ueda H, Yamagishi M. Cystic
37. Heyer CM, Kagel T, Lemburg SP, Bauer TT, Nicolas tumour of the atrioventricular node. Heart.
V. Lipomatous hypertrophy of the interatrial septum: 2003;89:122.
a prospective study of incidence, imaging findings, 46. Paniagua JR, Sadaba JR, Davidson LA, Munsch CM.
and clinical symptoms. Chest. 2003;124:2068–73. Cystic tumour of the atrioventricular nodal region:
38. Basso C, Barbazza R, Thiene G. Images in cardiovas- report of a case successfully treated with surgery.
cular medicine. Lipomatous hypertrophy of the atrial Heart. 2000;83:E6.
septum. Circulation. 1998;97:1423. 47. Burke AP, Ribe JK, Bajaj AK, Edwards WD, Farb A,
39. Schrepfer S, Deuse T, Detter C, Treede H, Koops A, Virmani R. Hamartoma of mature cardiac myocytes.
Boehm DH, Willems S, Lacour-Gayet F, Hum Pathol. 1998;29:904–9.
Reichenspurner H. Successful resection of a symp- 48. Burke AP, Gatto-Weis C, Griego JE, Ellington KS,
tomatic right ventricular lipoma. Ann Thorac Surg. Virmani R. Adult cellular rhabdomyoma of the heart:
2003;76:1305–7. a report of 3 cases. Hum Pathol. 2002;33:1092–7.
Primary Cardiac Tumors
in the Pediatric Age 5
Massimo A. Padalino, Cristina Basso,
Ornella Milanesi, Gaetano Thiene, and Giovanni Stellin
of cardiac tumor was possible in 67 children among

Introduction 38,952 who were evaluated between 1980 and 1998
(0.17%) [6]. Surely, the real incidence of this dis-
Most of primary cardiac tumors in the pediatric ease is greater than previously thought, mostly
age group are benign. However, they may cause because of improved cardiac imaging techniques.
major symptoms because of their intracardiac Although myxomas are the most common car-
position and/or dimensions [1–9]. In addition, diac tumors in adults [7, 8], in the pediatric age
since up to 10% of cardiac tumors may be malig- the most frequent heart tumors are rhabdomyo-
nant, a precise histopathologic diagnosis is of mas (45%), followed by fibromas (25%), myxo-
paramount importance for a proper diagnosis and mas (10–15%), and intrapericardial teratomas
therapeutical plan [3, 7]. (10%) [4, 6, 9–15]. In addition, rhabdomyomas
Cardiac tumor prevalence in the pediatric age is are the most common cardiac neoplasms in the
not easy to assess. Postmortem examination data neonate and infant, while in teenagers myxomas
account for an overall incidence of cardiac tumors occur more often [3, 6].
in the pediatric population ranging between 0.028 Due to the peculiar characteristics of each type
and 0.08% [4], and 14.2% of all tumors occur in of tumor, they will be discussed separately.
patients younger than 16 years of age [5].
Based on recent data from the Cardiovascular
Program at Boston Children’s Hospital, diagnosis Primary Benign Cardiac Tumors
Rhabdomyoma
M.A. Padalino, M.D., Ph.D. (*) • G. Stellin, M.D. Rhabdomyomas represent the most common
Pediatric Cardiac Surgery, Department of Cardiac, heart neoplasms in pediatric age, with an esti-
Thoracic and Vascular Science, Azienda Ospedaliera-
mated prevalence of 45–63% [1, 2,15]. Diagnosis
University of Padua Medical School, Via N. Giustiniani 2,
Padua 35128, Italy may be prenatal (24% in the Boston Children’s
e-mail: massimo.padalino@unipd.it Hospital experience) [6], but it is often achieved
C. Basso M.D., Ph.D. • G. Thiene M.D. at birth. Children may be asymptomatic or only
Pathological Anatomy, Department of Cardiac, mildly symptomatic, despite an extensive
Thoracic and Vascular Sciences, Azienda Ospedaliera- infiltration of the myocardium, and presenting
University of Padua Medical School, via A. Gabelli, 61,
only with a cardiac murmur at physical examina-
Padua 35121, Italy
tion [4, 9]. Usually, prenatal diagnosis occurs
O. Milanesi M.D.
when arrhythmias, hydrops, delayed fetal growth,
Pediatric Cardiology, Department of Pediatrics, Azienda
Ospedaliera-University of Padua Medical School, or family history for tuberous sclerosis have been
via N. Giustiniani, 2, Padua 35128, Italy detected on routine fetal screening [16].

60 M.A. Padalino et al.
Rhabdomyomas are usually multiple, well- [19, 23]. Most common electrocardiographic
defined, whitish or grayish nodular masses [2–4, 6]; abnormalities are left axial deviation, atrial
they are single masses in only 10% of the cases and/or ventricular enlargement, ST elevation,
[2, 3]. They may appear everywhere in the heart, bundle branch block, various degrees of atrio-
more often in the ventricular myocardium [2–4, ventricular block [1, 12, 19].
9, 13]. Mostly intramural, they may sometimes The chest X-ray may be absolutely normal, or
protrude into the ventricular cavity, or they may show cardiomegaly and pulmonary edema in the
appear as pedunculated or sessile masses [17] most compromised patients [1, 4, 12, 19].
(Fig. 5.1a). Two-dimensional echocardiography remains
At histology, rhabdomyomas typically the main diagnostic tool. Typically, rhabdomyo-
present with enlarged vacuolated cells, with mas are multiple, well-circumscribed nodular
sparse cytoplasm with glycogen deposits and masses, which are highly echogenic, either intra-
so-called “spider” cell appearance, i.e., cells mural or pedunculated intracavitary (Fig. 5.1a,b),
characterized by cytoplasm radial extensions and localized everywhere in the myocardium
with contractile myofilaments from the central [17–23]. Rhabdomyomas present with a homo-
nucleus to the cell periphery [3, 7, 8] (Fig. 5.1b). geneous echogenicity due to the absence of
Immunohistochemical studies show the typical fibrosis, necrosis, calcification, as well as cystic
features of striated muscle cells (myoglobin, and hemorrhagic areas. This is an important fea-
desmin, actin, and vimentin positive), thus ture to distinguish them from thrombi, myxomas,
confirming the diagnosis. At transmission elec- and other tumors [6]. In addition, pericardial
tron microscopy, rhabdomyoma cells look like effusion is rarely detected at echocardiographic
myocytes with abundant glycogen, rare mito- examination [6].
chondria, and intercalated disks sparse all Rhabdomyomas are frequently associated
around the periphery of the cell instead of with tuberous sclerosis (86%) [19, 23], while
being localized at the cell poles. about 50% of children with tuberous sclerosis
Clinical features of rhabdomyomas depend on have a cardiac rhabdomyoma. Tuberous sclerosis
their localization, number and dimensions [18]: is an autosomal dominant disease, with variable
for example, a large intramural or intracavitary penetrance and expression, which may poten-
mass may cause ventricular outflow obstruction, tially involve all organs, including the brain,
or atrioventricular or semilunar valve distortion pancreas, kidney, skin, and retina. Usual is the
[3, 11, 18]. Congestive heart failure, respiratory association with epilepsy (due to neurofibroma-
distress, or even low cardiac output syndrome tosis lesions), mental retardation (evident by 1
may occur in neonates or infants [13, 17–19]. In year of age), and skin lesions.
the most severe cases, the ventricular obstruction Almost 50% of patients with rhabdomyoma
may even mimic a severe subvalvar aortic steno- present with a family history of tuberous sclero-
sis or hypoplastic left heart syndrome or pulmo- sis. Recently, two genes have been found to be
nary stenosis [20–22]. Exceptionally, the tumoral associated with tuberous sclerosis: TSC1, which
masses may infiltrate diffusely the myocardium, codifies for the protein hamartin (9q34); and
as to cause a severe contractile and diastolic dys- TSC2, which codifies for the protein tuberin
function, even mimicking a restrictive cardiomy- (16p13.3) [24, 25]. These two proteins are
opathy [12]. involved in the tumor suppression mechanism,
In the literature, all the commonest arrhyth- but their precise role in cardiac tumor develop-
mias (including sudden death) have been ment remains still unknown.
described in association with cardiac rhab- The natural history of rhabdomyomas is char-
domyomas [1, 2, 12, 19, 23]. Direct compres- acterized by the possibility of spontaneous regres-
sion of the conduction system may account for sion, which may be partial or complete [3, 4, 7,
atrial or supraventricular tachyarrhythmias, 11, 14]. For this reason, surgery is reserved only to
such as the Wolff Parkinson White syndrome severely symptomatic patients; when symptoms
5 Primary Cardiac Tumors in the Pediatric Age 61
Fig. 5.1 Rhabdomyoma in a 7-month-old child with a lar outflow tract obstruction due to an endocavitary mass
systolic murmur due to subaortic stenosis (modified from attached to the anterolateral wall in the subaortic area. (b)
De Dominicis et al. [22]). Reprinted with permission of At histology, the resected mass shows the pathognomonic
the Italian Society of Cardiology. (a) Two-dimensional spider cells with cytoplasmatic myofibrils radiating to the
echocardiography, subcostal view: note the left ventricu- cell periphery (hematoxylin–eosin stain)
are mild or even absent, clinical follow-up, associ- Fibroma

ated with oral medication, is usually indicated [4, Cardiac fibroma is the second most frequent type
11, 26]. The most common reason for surgical of cardiac tumor in the pediatric age (about 20%)
referral is ventricular arrhythmias, which do not [1–4, 7, 9, 11]. Although the diagnosis is more
respond to drug therapy and obstruction of ven- frequent in late childhood or in teenagers, the
tricular outflows. Surgical resection of the tumoral tumor may become symptomatic also in early
mass aims to remove all tissue causing clinical childhood or even in the neonate [27, 28]
symptoms/signs and ideally should be as radical as (Fig. 5.2). Macroscopically at gross examination,
possible. However, the well-known possibility of the fibroma usually is a single, solid, well-defined,
cardiac mass regression allows to safely perform a whitish and whorled mass, almost invariably
partial resection whenever a greater removal of tis- intramural, and usually located in the right or left
sue may jeopardize important cardiac structures ventricular free walls, or in the interventricular
[3, 4, 10–12, 15, 18–23]. This surgical strategy septum [1–5, 7]. These tumors may reach huge
presents excellent early and long-term outcomes dimensions, even up to 8 cm of diameter, to
[3, 26]. obstruct the ventricular cavity [27, 28].
Fig. 5.2 Fibroma in a neonate who underwent heart free wall (LV). (b) Macroscopically, by opening the
transplant at 38 days of life, after prenatal echocardio- explanted heart along the obtuse margin, a large intramu-
graphic diagnosis of left ventrciular mass (modified from ral oval-shaped, whorled and whitish mass, obstructing
Valente et al. [27]). Reprinted with permission of the the mitral valve orifice, is visible. (c) At histology,
Italian Society of Cardiology. (a) Fetal two-dimensional fibromatous proliferation with abundant collagen fibers
echocardiography of the tumor (T) of the left ventricular (Heidenhain trichrome stain)
At histology, the fibroma consists of a homo- mass, which may be excised completely and
geneous mass of fibroblasts mixed with abundant safely even if huge [28] (Fig. 5.3). However,
collagen and elastic fibers, and often entrapping whenever a total resection could be potentially
some cardiomyocytes. They are not encapsulated dangerous, partial resection is also effective in
and often extend into the surrounding myocar- the early and long term; cavo-pulmonary shunt
dium. The amount of cells decreases during the anastomosis in cases with a very large fibroma of
time, while the collagen content increases [3, 5, the right ventricle has been even performed [4, 32].
7, 27]. Occasionally, these tumors may present In the most severe cases, with massive infiltration
lymphomonocyte aggregates, and areas of of the myocardium, heart transplant can be the
calcification which are detected on chest X-ray or only therapeutic option [15, 27].
CT scan [12]. Spontaneous regression or malig-
nant degeneration has never been described [1, 2, Myxoma
4, 5, 7, 9]. Myxoma is the most frequent cardiac tumor in
Clinical symptoms are mostly caused by the adults [7, 8], but it represents only the 10–15% of
dimensions of the mass and from its location. cardiac tumors in the pediatric age [1–5]. It is
Occasionally, they may be asymptomatic despite more often diagnosed in teenagers, while it is
large dimensions and be an incidental finding rare but clinically very dramatic in infants [33]
[29]. More commonly, since they can infiltrate (Fig. 5.4).
the ventricular septum myocardium and the con- Myxoma is usually sporadic, but 10% of
duction axis, fibromas may cause ventricular patients present an association with the so-called
arrhythmias and conduction disturbances which Carney complex, with autosomal dominant inher-
may even be lethal causing sudden death [4, 9, itance [34, 35].
30]. Whenever the mass is large and intramural, it Intracardiac myxomas are very friable, poly-
may protrude in the ventricular outflow tract and poid, gelatinous masses, sessile or pedunculated,
cause severe mechanical obstruction, together yellowish or reddish. When present, the stalk is
with contractile dysfunction and severe conges- typically attached to the endocardium of the fossa
tive heart failure [1, 3–5, 9, 27, 28]. ovalis. Although they are usually single masses,
At echocardiography, fibromas appear as solid multiple or biatrial masses have been reported in
single intramural masses, homogeneously dense, the literature [7, 36]. They are more frequently
with a diameter ranging from few mm to some localized in the left atrium, but they have been
cm, and usually involving the ventricular free described everywhere inside the heart [1–5, 7, 8,
wall or the interventricular septum [3, 4, 9]. 33].
Cardiac magnetic resonance imaging (MRI) Microscopically, myxomas present with a
enables the physician to achieve a better definition myxoid mucopolysaccharidic matrix containing
of the mass and of its relation with the surround- fusiform, stellate, or polygonal cells, and some-
ing structures [28] (Fig. 5.3). times aggregated in pseudovascular structures [7]
Noteworthy, about 3% of patients with Gorlin (Fig. 5.5).
syndrome (or nevoid basal cell carcinoma syn- Myxomas are benign neoplasms, but they may
drome) show cardiac fibromas [31]. This is an have a “malignant” behavior because of their
autosomal dominant disorder that affects many dimensions, location, recurrency, or systemic
areas of the body with an increased risk of devel- embolization risk [8, 13, 33]. A malignant histo-
oping various tumors and is due to mutations in logic variant has never been described.
the PTCH1, a tumor suppressor gene. The myxoma usually presents with three types
Surgical referral depends on the presence of of clinical symptoms and signs, i.e., obstructive,
clinical symptoms [3, 15]. Although regression embolic, and constitutional.
has never been described, the asymptomatic Since they are pedunculated and mobile, myx-
patients are usually followed up clinically. Aim omas in the left or right atrium may impinge into
of surgical intervention is the resection of the the mitral or tricuspid valve orifice, thus blocking
Fig. 5.3 Fibroma in a 5-month-old infant with congestive involving the anterior wall of the right ventricle, with an
heart failure and liver enlargement (modified from Padalino almost complete obliteration of the ventricular cavity and
et al. [28]). Reprinted with permission of the Italian Society of the pulmonary outflow tract. (b) Intraoperative image of
of Cardiology. (a) Cardiac magnetic resonance imaging in the mass involving the right ventricular free wall, which
sagittal view: note a large homogeneous mass, 6 × 4 × 5 cm, required a ventricular patch plasty after resection
the blood flow during diastole. This hemody- prolapse into the mitral valve orifice during dias-
namic block can cause transient heart failure, tole. These clinical manifestations are often
recurrent syncope (Fig. 5.4b), or even sudden related to the patient position, typically occurring
death [8, 13, 32]. Myxomas with a long pedicle when he or she is standing up; on the contrary,
may even protrude into the ventricular cavity the myxoma moves away from the valve with
and cause outflow tract obstruction. At physical symptoms relief while lying down. Finally,
examination, a characteristic mesodiastolic mur- because of the fast growth of the mass in a small
mur or “tumor plop” is often heard, due to mass atrial cavity, cardiac myxoma in children usually
Fig. 5.4 Myxoma in a 6-year-old child with congestive (systole): note the presence of a mass in the left atrium.
heart failure (modified from Padalino et al. [32]). (c) Two-dimensional color Doppler echocardiography
Reprinted with permission of the Italian Society of (diastole): note the mass prolapse into the mitral valve
Cardiology. (a) Chest X-ray showing cardiomegaly. orifice. (d) The resected mass is gelatinous, whitish, with
(b) Two-dimensional color Doppler echocardiography a fine villous surface
presents with severe congestive heart failure and Raynaud’s syndrome, anemia, increased C
low cardiac output syndrome [3, 33]. reactive protein, low platelet count, arthralgias,
The embolic risk is related to the intrinsic fri- myalgias, mostly due to IL-6 release, which is
able structure of this tumor, which may embolize associated with protein synthesis and production
either in the systemic or in the pulmonary circu- of inflammatory mediators [37]. All these features
lation, depending on its location. Emboli may usually disappear soon after myxoma resection.
consist of fragments either of the myxoma or of At echocardiography, myxoma appears as a
the thrombus that frequently develop on the sur- lobulated intracavitary mass which is attached
face of the tumor itself. Paradoxical embolism with a thin stalk to the endocardium. The color
may be caused by a myxoma of the right atrium Doppler evaluation enables the estimation of
through a patent foramen ovale [4, 7–9]. Whenever obstruction or regurgitation of the mitral or tri-
a child presents with embolic manifestations, an cuspid valves. In addition, whenever the myxoma
accurate two-dimensional echocardiographic is on the right side of the heart, right ventricular
examination must be done as soon as possible to pressure measurement is useful to rule out pul-
rule out a cardiac myxoma. monary embolism. Ventricular myxoma, although
The so-called “constitutional” symptoms or rare, may cause dynamic obstruction of the
signs are aspecific and include fever, weight loss, outflow tract.
Fig. 5.5 Same case of Fig. 5.4. Reprinted with permis- dant myxoid matrix (Alcian PAS ×3). (b) At higher
sion of the Italian Society of Cardiology. (a) Histology magnification, single cells embedded within a myxoid
confirms the villous structure of the tumor, with an abun- matrix are visible (hematoxylin eosin stain, ×120)
Due to the unpredictable risk of tumor embo- Intrapericardial Teratoma (Germ Cell
lization, diagnosis of intracardiac myxoma is by Tumor)
definition an indication to prompt surgical resec- Germ cells tumors are classified depending on
tion of the mass [3, 6, 7, 15, 33]. The surgeon the germ they derive from, such as seminoma (or
must remove not only the myxoma, but also the dysgerminoma), embrional carcinoma, yolk sac
endocardial tissue which surrounds the thin stalk tumor, choriocarcinoma, and teratoma [2].
of the mass, in order to prevent the well-known Among more than 100 cases of intrapericardial
risk of myxoma recurrence. Moreover, since the germ cell tumors reported in the literature, 90%
mass is highly friable, it is imperative to avoid of teratomas involve the pericardium, while only
manipulation of the heart before the cardio-pul- 10% involves the myocardium. Diagnosis occurs
monary bypass is established and the aorta cross- typically within the first month of life [38, 39].
clamped. They are very rare, usually benign, in contrast
Fig. 5.6 Teratoma in a 12-day-old neonate with pericar- (b) Transverse panoramic histologic section of the resected
dial effusion at birth (modified from Padalino et al. [3]). mass: note the typical cystic structure (Heidenhain
Reprinted with permission of the Italian Society of trichrome stain). (c) At immunohistochemistry, multiple
Cardiology. (a) Two-dimensional echocardiography, sub- immature elements of different embryonic origin are vis-
costal four-chamber view: note the presence of a disho- ible (pan-keratin antibody). (d) Close-up of (c): note
mogeneous and cystic mass at the root of the great vessels. intestinal epithelium (pan-keratin antibody)
with those occurring in adult age which are vena cava, and may cause compression of these
mostly malignant germ cell tumors. latter structures but also of the right atrium and
A teratoma is an encapsulated tumor with tissue ventricle and of the pulmonary artery [40]. They
or organ components resembling normal derivatives may grow up to reach even 15 cm of diameter, to
of all three germ layers, although sometimes all three become even bigger than the heart itself.
germ layers are not identifiable (and are probably The neonate with an intrapericardial teratoma
misclassified as bronchogenic cysts). Tissue compo- is usually severely symptomatic. In fact, because
sition may be highly variable, since teratomas may of the large dimensions and the intrapericardial
contain hair, teeth, bone, cartilage, lung or gastro- position, the mass usually compresses the sur-
enteric and many other tissues [4, 7–9, 38, 39]. rounding cardiac and vascular structures, and
Teratomas are generally solitary, encapsulated even the pulmonary parenchyma. Pericardial
cystic masses with intervening solid areas, often effusion is commonly associated. This may concur
connected to the aortic root or to the pulmonary in causing a severe respiratory distress, cardiac
artery by means of a thin vascularized pedicle tamponade, and low cardiac output syndrome
(Fig. 5.6). They are usually localized at the base of that may be fatal if prompt diagnosis and treat-
the heart, anterior to the aorta, close to the superior ment are not provided [39, 40].
Fig. 5.7 Hemangioma in a 5 days old neonate, with of a dyshomogeneous mass inside the right atrium.
paroxysmal supraventricular tachycardia at birth and a (b) Surgical view after right atriotomy. (c) Macroscopic
diagnosis of right atrial mass (modified from Padalino view of the resected mass: note the multiple vascular
et al. [32]). Reprinted with permission of the Italian spaces filled of blood. (d) Histology confirms the diag-
Society of Cardiology. (a) Two-dimensional echocar- nosis of benign cavernous hemangioma (Heidenhain
diography, subcostal four-chamber view: note the presence trichrome stain)
Diagnosis is usually achieved with two- vascularised pedicle from the ascending aorta,
dimensional echocardiography during both the and from the adjacent pericardium. Since the
fetal and the neonatal period [41, 42]. The tera- mass is typically extracardiac, cardiopulmonary
toma looks like a single pedunculated mass, bypass is not required but a careful dissection and
inside the pericardium; it appear as a dyshomog- ligation of the aorta and/or pulmonary artery is
enous mass because of the presence of cystic and needed to prevent massive hemorrhage being the
calcified areas. Two-dimensional echocardiogra- blood supply from the root of these vessels [44].
phy allows a precise evaluation of the mass
dimensions, location, and associated pericardial Hemangioma
effusion, thus guiding the physician for pericar- Cardiac hemangioma and all other tumors derived
dial fluid drainage [40]. Fetal echocardiography from vascular tissue (lymphangiomas) are rare
enables an early diagnosis to plan a prompt surgi- benign cardiac tumors which may arise every-
cal management at birth [40, 41]. Surgical resec- where in the heart. Two-dimensional echocar-
tion of the mass is often lifesaving and effective, diography shows multiple echo-transparent
since tumor relapse or pericardial effusion recur- masses, often associated with pericardial effusion,
rence has never been reported [43]. Surgery con- which may grow within the myocardium but also
sists in a complete resection of the mass and of its intracardiac (Fig. 5.7) [45, 46]. They are frequently
clinically silent as to be an incidental finding dur-

ing routine examination; sometimes they may
trigger arrhythmias or cause obstructive symp-
toms. In asymptomatic patients, clinical and
echocardiographic follow-up is usually enough,
On the contrary, surgical resection is indicated
whenever the mass causes symptoms and is well
defined and circumscribed. However, if the mass
is diffusely infiltrating the myocardium, cardiac
transplantation may be the only therapeutic
option [45, 46].
Histiocytoid Cardiomyopathy
This lesion is also known as oncocytic cardio-
myopathy, Purkinje cell tumor or hamartoma,
focal lipid cardiomyopathy, idiopathic infantile Fig. 5.8 Purkinje cell tumor in a 13-month-old child pre-
cardiomyopathy [47, 48]. It occurs mostly in the senting with cyanosis and dyspnea. Reprinted with per-
first 2 years of life. mission of the Italian Society of Cardiology. Histology
Concerning its pathogenesis, nowadays it is shows focal islands of Purkinje-like cells, clearly distinct
from the normal surrounding cardiomyocytes (hematoxy-
considered a tumor deriving from the cardio- lin–eosin stain)
myocyte with some Purkinje cell features,
although many other theories have been globin, myosin, and muscle-specific actin,
advanced including viral infections, myocardial whereas there is no expression of histiocyte
ischemia, glycogen storage disease, and mito- antigens.
chondrial cardiomyopathy. Echocardiography may reveal nodular depos-
Macroscopically, these masses present as sin- its on the ventricular endocardium or valves. If
gle or multiple subendocardial yellowish nodules left untreated, oncocytic cardiomyopathy may
or plaques, 1–15 mm in size. The most common have a fatal course in affected infants. Surgical
locations are the conduction system and the left excision or cryoablation of the multiple nodular
ventricle, but they may be also found in the right lesions is required for long-term cure, with a sur-
atrium and ventricle. In up to one-third of patients vival rate of 80% [26, 49]. A few cases of cardiac
the tumors may be associated with cardiac or ext- transplantation due to extensive disease have
racardiac anomalies such as atrial and ventricular been also reported.
septal defects, hypoplastic left heart syndrome,
cleft palate, and anomalies of the eyes, skin, and Other Benign Cardiac Tumors
central nervous system. Other types of benign cardiac tumors in infancy
Microscopically, these multifocal islands con- are extremely rare and include lipoma and papil-
tain large, polygonal, or oval cells, with a coarse loma, which may occur anywhere inside the heart
granular pale eosinophilic cytoplasm (Fig. 5.8). [1, 2, 4, 9].
The cytoplasm is filled with abundant, bizarre Finally, a very rare and peculiar type of car-
looking mitochondria. The term oncocytic cardi- diac tumor is the inflammatory myofibroblastic
omyopathy describes the process of the granules tumor (or inflammatory pseudotumor, plasma
(mitochondria) displacing the working myofibrils. cell granuloma), a proliferation of uncertain
When compared to rhabdomyoma, there are histogenesis. Histologically, it is composed of
many mitochondria with no T tubules or complex spindled myofibroblasts, fibroblasts, and chronic
intercellular junctions, and no vacuoles or inflammatory cells including lymphocytes,
myofibrils (Fig. 5.8). At immunohistochemistry, macrophages, plasma cells, and eosinophils
tumor cells react with antibodies to desmin, myo- [49]. Grossly, they are endocardial lesions
which often have a narrow attachment to the 8. Bortolotti U, Maraglino G, Rubino M, Santini F,
endocardium and protrude into the cardiac cham- Milano A, Fasoli G, Livi U, Thiene G, Gallucci V.
Surgical excision of intracardiac myxomas: a 20 year
bers. There is often organizing fibrin thrombus on follow up. Ann Thorac Surg. 1990;49:449–53.
the surface. Echocardiographic evaluation shows 9. Freedom RM, Lee KJ, MacDonald C, Taylor G.
a homogeneous intracavitary mass that often fills Selected aspects of cardiac tumors in infancy and
completely the cardiac cavity. It may be silent or childhood. Pediatr Cardiol. 2000;21:299–316.
10. Jacobs JP, Anastasios KK, Holland FW, Hershowitz
can cause obstructive symptoms; surgery is usu- K, Ferrer PL, Perryman RA. Surgical treatment for
ally indicated [50]. cardiac rhabdomyomas in children. Ann Thorac Surg.
1994;58:1552–5.
11. Becker AE. Primary heart tumors in the pediatric age
group: a review of salient pathologic features relevant
Primary Malignant Cardiac Tumors in for clinicians. Pediatric Cardiol. 2000;21:317–23.
the Pediatric Age 12. Bini RM, Westaby S, Bargeron Jr LM, Pacifico AD,
Kirklin RW. Investigation and management of pri-
Malignant primary cardiac tumors are extremely mary cardiac tumors in infants and children. J Am
Coll Cardiol. 1983;2:351–7.
rare in infancy and pediatric age. There no series in 13. Sallee D, Spector ML, van Heeckeren DW, Patel CR.
the literature to date. In a review of neonatal and Primary pediatric cardiac tumors: 17 year experience.
fetal heart tumors published prior to 2004, sar- Cardiol Young. 1999;9:155–62.
coma represented 0 and 2% of total cases, respec- 14. Chan HSL, Sonley MJ, Moes F, Daneman A, Smith
CR, Martin DJ. Primary and secondary tumors of
tively [51]. It is suspected that several pediatric childhood involving the heart, pericardium and great
heart tumors reported in the medical literature as vessels. Cancer. 1985;56:825–36.
sarcomas are probably misdiagnosed inflammatory 15. Padalino MA, Vida VL, Boccuzzo G, Tonello M,
myofibroblastic tumors (see above). Sarris GE, Berggren H, Comas JV, Di Carlo D, Di
Donato RM, Ebels T, Hraska V, Jacobs JP, Gaynor JW,
Metras D, Pretre R, Pozzi M, Rubay J, Sairanen H,
Schreiber C, Maruszewski B, Basso C, Stellin G. Surgery
for primary cardiac tumors in children: early and late
References results in a multicenter European congenital heart sur-
geons association study. Circulation. 2012;126:22–30.
1. Fyler DC. Report of the New England regional infant 16. Deeg KH, Voigt HJ, Hofbeck M, Singer H, Kraus J.
cardiac program. Pediatrics. 1980;65:376–461. Prenatal ultrasound diagnosis of multiple cardiac
2. Burke AP, Veinot JP, Loire R, Virmani R, Tazelaar H, rhabdomyomas. Pediatr Radiol. 1990;20:291–2.
Kaniya H, Araoz PA, Watanabe G. Tumours of the 17. Fischer DR, Beerman LB, Park SC, Bahnson HAT,
heart. In: Travis WD, Brambilla E, Muller-Hermelink Fricker FJ, Mathews RA. Diagnosis of intracardiac
HK, Harris CC, editors. Pathology and genetics of rhabdomyoma by two dimensional echocardiography.
tumours of the lung, pleura, thymus and heart. Lyon: Am J Cardiol. 1984;53:978–97.
IARC Press; 2004. p. 249–88. 18. Roberts WC. Primary and secondary neoplasms of the
3. Padalino MA, Basso C, Milanesi O, Vida VL, Svaluto heart. Am J Cardiol. 1997;80:671–82.
Moreolo G, Thiene G, Stellin G. Surgically treated 19. Shaher RM, Mintzer J, Farina M, Alley R, Bishop M.
primary cardiac tumors in early infancy and child- Clinical presentation of rhabdomyoma of the heart in
hood. J Thorac Cardiovasc Surg. 2005;129:1358–63. infancy and childhood. Am J Cardiol. 1972;30:95–103.
4. Beghetti M, Gow RM, Haney I, Mawson J, Williams WG, 20. Abdel-Rahman U, Ozaslan F, Esmaeili A, Moritz A.
Freedom RM. Pediatric primary benign cardiac tumors: A giant rhabdomyoma with left ventricular inflow
a 15 year review. Am Heart J. 1997;134:1107–14. occlusion and univentricular physiology. Thorac
5. Burke A, Virmani R. Tumors of the heart and great Cardiovasc Surg. 2005;53:259–60.
vessels. Atlas of tumor pathology, series 3, fascicle 21. Friedberg M, Silverman NH. Right ventricular outflow
16. Washington, DC: Armed Force Institute of tract obstruction in an infant. Heart. 2005;91:748.
Pathology; 1995. 22. De Dominicis E, Frigiola A, Thiene G, Menicanti L,
6. Marx GA, Moran AM. Cardiac tumors. In: Allen HD, Bozzola L, Finocchi G. Subaortic stenosis by solitary
Adams FH, Moss AJ, editors. Moss & Adams’s heart rhabdomyoma. Successful excision in an infant fol-
disease in infants, children and adolescents: including lowing 2D echocardiogram and Doppler diagnosis.
the fetus and young adult. Philadelphia, PA: Lippincott Chest. 1989;95:470–2.
Williams & Wilkins; 2001. p. 1432–45. 23. Bosi G, Lintermans JP, Pellegrino PA, Svaluto
7. Basso C, Valente M, Poletti A, Casarotto D, Thiene G. Moreolo G, Vliers A. The natural history of cardiac
Surgical pathology of primary cardiac and pericardial rhabdomyoma with and without tuberous sclerosis.
tumors. Eur J Cardiothorac Surg. 1997;12:730–8. Acta Pediatr. 1996;85:928–31.
24. Povey S, Burley MW, Attwood J, Benham F, Hunt D, 37. Kanda T, Umeyama S, Sasaki A, Nakazato Y,
Jeremiah SJ, Franklin D, Gillett G, Malas S, Robson Morishita Y, Imai S, Suzuki T, Murata K. Interleukin-6
EB. Two loci for tuberous sclerosis: one on 9q34 and and cardiac myxoma. Am J Cardiol. 1994;74:965–7.
one on 16p13. Ann Hum Genet. 1994;58:107–27. 38. Sumner TE, Crowe JE, Klein A, McKone RC, Weaver
25. van Slegtenhorst M, de Hoogt R, Hermans C, Nellist RL. Intrapericardial teratoma in infancy. Pediatr
M, Janssen B, Verhoef S, Lindhout D, van den Radiol. 1980;10:51–3.
Ouweland A, Halley D, Young J, Burley M, Jeremiah 39. Agozzino L, Vosa C, Arciprete P, de Leva F, Cotrufo
S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne M. Intrapericardial teratoma in the newborn. Int J
J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Cardiol. 1984;5:21–8.
Tachataki M, Ravine D, Sampson JR, Reeve MP, 40. Benatar A, Vaughan J, Nicolini U, Corrin B, Licoln C.
Richardson P, Wilmer F, Munro C, Hawkins TL, Sepp Prenatal pericardiocentesis: its role in the manage-
T, Ali JB, Ward S, Green AJ, Yates JR, Kwiatkowska ment of intrapericardial teratoma. Obstet Gynecol.
J, Henske EP, Short MP, Haines JH, Jozwiak S, 1992;79:856–9.
Kwiatkowski DJ. Identification of the tuberous scle- 41. Cyr DR, Guntheroth WG, Nyberg DA, Smith JR,
rosis gene TSC1 on chromosome 9q34. Science. Nudelman SR, Ek M. Prenatal diagnosis of an intrap-
1997;277:805–8. ericardial teratoma. A cause for non immune hydrops.
26. Takach TJ, Reul GI, Ott DA, Cooley DA. Primary car- J Ultrasound Med. 1988;7:87–90.
diac tumors in infants and children: immediate and 42. Farooki ZQ, Arciniegas E, Hakimi M, Clapp S,
long term operative results. Ann Thorac Surg. Jackson W, Green EW. Real time echocardiographic
1996;62:559–64. features of intrapericardial teratoma. J Clin Ultrasound.
27. Valente M, Cocco P, Thiene G, Casula R, Poletti A, 1982;10:125–8.
Milanesi O, Fasoli G, Livi U. Cardiac fibroma and 43. Banfield F, Dick II M, Behrendt DM, Rosenthal A,
heart transplantation. J Thorac Cardiovasc Surg. Pescheria A, Scott W. Intrapericardial teratoma: a new
1993;106:1208–12. and treatable cause of hydrops fetalis. Am J Dis Child.
28. Padalino MA, Basso C, Thiene G, Stellin G. Giant 1980;134:1174–5.
right ventricular fibroma in an infant. Circulation. 44. Paw PT, Jamieson SW. Surgical management of intra-
2002;106:386. pericardial teratoma diagnosed in utero. Ann Thorac
29. Takahashi K, Imamura Y, Ochi T, Hamanda M, Ito T, Surg. 1997;64:552–4.
Hiwada K, Kokubu T. Echocardiographic demonstra- 45. Tabry IF, Nassar VH, Rizk G, Touma A, Dagher IK.
tion of an asymptomatic patient with left ventricular Cavernous hemangioma of the heart: case report and
fibroma. Am J Cardiol. 1984;53:981–2. review of literature. J Thorac Cardiovasc Surg.
30. Filiatrault M, Beland MJ, Neilson KA, Paquet M. 1975;69:415–20.
Cardiac fibroma presenting with clinically significant 46. Grenadier E, Margulis T, Palant A, Safadi T, Merin G.
arrhythmias in infancy. Pediatr Cardiol. 1991; Huge cavernous hemangioma of the heart: a com-
12:118–20. pletely evaluated case report and review of the litera-
31. Vaughan CJ, Veugelers M, Basson CT. Tumors and ture. Am Heart J. 1989;117:479–81.
the heart: molecular genetic advances. Curr Opin 47. Rossi L, Piffer R, Turolla E, Frigerio B, Coumel P,
Cardiol. 2001;16:195–200. James TN. Multifocal Purkinje-like tumor of the
32. Beghetti M, Haney I, Williams WG, Mawson J, heart. Occurrence with other anatomic abnormalities
Freedom RM, Gow RM. Massive right ventricular in the atrioventricular junction of an infant with junc-
fibroma treated with partial resection and a cavopul- tional tachycardia, Lown–Ganong–Levine syndrome,
monary shunt. Ann Thorac Surg. 1996;62:882–4. and sudden death. Chest. 1985;87:340–5.
33. Padalino MA, Basso C, Svaluto Moreolo G, Thiene 48. Ferrans VJ, McAllister Jr HA, Haese WH. Infantile
G, Stellin G. Left atrial myxoma in a child. Case cardiomyopathy with histiocytoid change in cardiac
report and review of literature. Cardiovasc Pathol. muscle cells. Report of six patients. Circulation.
2003;12:233–6. 1976;53:708–19.
34. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go 49. Garson A, Smith RT, Moak JP, Kearney DL, Hawkins
VL. The complex of myxomas, spotty pigmentation, EP, Titus JL, Cooley DA, Ott DA. Incessant ventricu-
and endocrine overactivity. Medicine. 1985;64:270–83. lar tachycardia in infants: myocardial hamartomas and
35. Carney JA, Hruska LS, Beauchamp GD, Gordon H. surgical cure. J Am Coll Cardiol. 1987;10:619–26.
Dominant inheritance of the complex of myxomas, 50. Rose AG, McCormick S, Cooper K, Titus JL.
spotty pigmentation, and endocrine overactivity. Inflammatory pseudotumor (plasma cell granuloma)
Mayo Clin Proc. 1986;61:165–72. of the heart. Report of two cases and literature review.
36. Cilliers AM, van Unen H, Lala S, Vanderdonck KH, Arch Pathol Lab Med. 1996;120:549–54.
Hartman E. Massive biatrial myxomas in a child. 51. Burke A, Virmani R. Pediatric heart tumors.
Pediatr Cardiol. 1999;20:150–1. Cardiovasc Pathol. 2008;17:193–8.
Primary Malignant Tumors
of the Heart 6
Marialuisa Valente, Stefania Rizzo, Ornella Leone,
and Cristina Basso
There are a few differences in this recent

Introduction WHO classification compared to the previous
one utilized by the Armed Forces Institute of
Primary malignant tumors of the heart are rare Pathology [2] (a) epithelioid hemangioendothe-
and are represented by sarcomas, primary lym- lioma has been introduced; (b) malignant fibrous
phomas, and malignant pericardial tumors. histiocytoma (MFH) and undifferentiated pleo-
According to the “WHO histological morphic sarcoma are regarded as synonyms and
classification of the tumors of the heart” [1] pri- cases reported in the past as osteosarcomas are
mary cardiac malignancies include: now considered as MFH with osseous differenti-
– Angiosarcoma ation; (c) myxosarcoma is thought to be a myxoid
– Epithelioid hemangioendothelioma variant of fibrosarcoma. Finally, other very rare
– Pleomorphic malignant fibrous histiocytoma primary cardiac tumors, like malignant schwan-
(MFH)/undifferentiated pleomorphic sarcoma noma, malignant rhabdoid tumor [2], and carci-
– Fibrosarcoma and myxoid fibrosarcoma nosarcoma [3] are not mentioned by the WHO
– Rhabdomyosarcoma classification.
– Leiomyosarcoma There is no TNM classification for primary
– Synovial sarcoma malignant cardiac tumors, and, due to their low
– Liposarcoma frequency, there is no specific grading scheme for
– Cardiac lymphoma sarcomas. Thus, the general criteria proposed for
– Primary malignant pericardial tumors (soli- grading malignant tumors of the soft tissues are
tary fibrous tumor, malignant mesothelioma, utilized also for the cardiac ones [4].
germ cell tumor) The two most widely used grading systems for
soft tissue sarcomas are those proposed by the
United States National Cancer Institute (NCI) [5]
and by the Fédération Nationale des Centres de
M. Valente, M.D. () • S. Rizzo, M.D.
• C. Basso, M.D., Ph.D. Lutte Contre le Cancer (FNCLCC) [6]. According
Pathological Anatomy, Department of Cardiac, to the latter, a histological score from 1 to 3 is
Thoracic and Vascular Sciences, assigned to each of three parameters, i.e., tumor
Azienda Ospedaliera-University of Padua Medical
differentiation, mitotic rate, and amount of necro-
School, via A. Gabelli, 61, Padua 35121, Italy
e-mail: marialuisa.valente@unipd.it sis in untreated primary soft tissue sarcomas. The
final grade is obtained by adding the three scores.
O. Leone, M.D.
Department of Pathology, S. Orsola-Malpighi Hospital, The grade has been demonstrated to be the main
Via Massarenti, 9, Bologna 40138, Italy predictive factor for metastases in soft tissue

74 M. Valente et al.
pleomorphic sarcoma, undifferentiated sarcoma Imaging. Two-dimensional echocardiography

and synovial sarcoma [7]. demonstrates an echogenic mass (Fig. 6.1a) in
The prognosis for cardiac sarcomas firstly the right atrium associated with pericardial effu-
depends on complete surgical resection. This sion and/or infiltration [20]. Cardiovascular mag-
is only rarely achieved, so adjuvant chemo- netic resonance imaging (MRI) reveals a nodular
therapy and more rarely radiotherapy are also and heterogeneous mass with focal areas of
given. Orthotopic heart transplantation [8 ] or increased signal intensity related to hemorrhage.
even autotransplantation [9 ] is an option in Enhancement along the vascular channels gives a
selected cases. “sunray” appearance [21]. Moreover, MRI allows
to distinguish between pericardial neoplasm and
pericardial effusion. On computed tomography
(CT) angiosarcoma appears as an inhomoge-
Angiosarcoma
neous mass, with high attenuation caused by
hemorrhage, and low attenuation in necrotic
This sarcoma with endothelial differentiation is
areas [20].
the most frequent primary malignant cardiac
tumor [10–14]. It has been reported with several Gross features. Angiosarcoma is usually a
synonyms such as hemangioendothelioma, cauliflower-like dark-red mass, projecting into
malignant hemangioendothelioma, hemangiosar- the right atrial cavity, with variable size and
coma, hemangioendothelial sarcoma, malignant poorly defined borders, infiltrating the pericar-
hemangioma, malignant angioendothelioma, and dium and causing hemorrhagic pericardial effu-
hemangioendotheliosarcoma. sion. Obstruction of the venae cavae, tricuspid
valve, right ventricle, and rarely the pulmonary
Epidemiology. Primary cardiac angiosarcomas can
artery may occur.
occur at any age (from 36 months to 80 years), but
they are more frequently diagnosed in the fourth Histopathological features. In two thirds of the
decade [15, 16]. There is no sex predilection. cases, angiosarcoma is well differentiated; irreg-
ularly shaped and anastomotic vascular channels
Localization. Angiosarcomas are usually located
are visible, admixed with papillary proliferation
within the right atrium, close to the atrio-ventric-
of bizarre endothelial cells, with large hyperchro-
ular sulcus, but they have been seldom reported
matic nuclei (Fig. 6.1b, c). In one third of the
also in the other cardiac chambers and in the
cases, tumor is poorly differentiated, composed
pericardium.
of solid clusters of oval and spindle-shaped cells
Clinical presentation. The diagnosis of angiosar- with eosinophilic cytoplasm and hyperchromatic
coma is usually difficult and late, as the clinical nuclei furnished with prominent nucleoli. Mitosis
picture, including constitutional symptoms (fever, and scattered extravascular red blood cells are
arthralgias, weakness and loss of weight) is frequently seen; areas of tumor necrosis and
nonspecific. The most common symptom is chest hemorrhage may be present. The immunohis-
pain [15], followed by right heart failure, haem- tochemical profile reflects the endothelial nature
orrhagic pericardial effusion and supraventricular of the malignant cells, which are strongly posi-
arrhythmias. Metastases to the lungs are fre- tive for CD31, CD34, and factor VIII (Fig. 6.1d).
quently present at diagnosis [17]; coagulation Ultrastructural studies rarely contribute to the
abnormalities are also observed [18]. diagnosis, because Weibel-Palade bodies, the
The diagnosis may be achieved through an ultrastructural markers of normal endothelial
endomyocardial biopsy due to frequent right cells, are very rare in the cells of angiosarcoma.
heart localization of the tumor [19], as well as However, other features such as pinocytic vesicles,
through an open pericardial biopsy in case of intermediate filaments, prominent rough endo-
pericardial infiltration with hemorrhagic effu- plasmic reticulum, Golgi apparatus, and associa-
sion. Cardiac rupture has been rarely described. tion with pericytes are present.
6 Primary Malignant Tumors of the Heart 75
Fig. 6.1 Angiosarcoma in 36- year-old woman, suffering biopsy of the mass: the myocardium appears infiltrated by
from dyspnea and fever (modified from Poletti et al. [19]). pleomorphic spindle cells with hyperchromatic nuclei
Reprinted with permission of the Italian Society of forming vascular channels (hematoxylin–eosin stain). (c)
Cardiology. (a) Two-dimensional echocardiogram, apical Immunostaining against myoglobin is strongly positive in
four-chamber view, showing an irregular, both endocavi- the normal myocardium but not in the neoplastic prolif-
tary and intramural large mass (arrows) in the right atrium eration. (d) The tumor cells arranged in vascular channels
(RA), extending into the right ventricle (RV), 6 × 8 cm in are positive to factor VIII (LV left ventricle)
size. (b) Histology of the transvenous endomyocardial
Genetic studies on angiosarcoma are extremely

limited. K-ras alterations [22] and clonal poly- Pleomorphic Malignant Fibrous
ploidy [23] have been identified. Histiocytoma/Undifferentiated
Pleomorphic Cardiac Sarcoma
Prognosis. Prognosis is extremely poor, usually
because of delayed diagnosis, when metastases,
According to the recent WHO classification of soft
in particular to the lungs, have already occurred
tissue tumors [4] malignant fibrous histiocytoma
[24]. Median survival is less than 1 year from the
(MFH) and undifferentiated pleomorphic sarcoma,
first operation [25]. Cardiac transplantation does
previously considered as separate entities, are now
not provide long-term survival [8].
regarded as synonyms. They are malignant undif-
ferentiated mesenchymal tumors. Three different
subtypes have been described (1) high grade MFH/
Epithelioid Hemangioendothelioma
undifferentiated pleomorphic sarcoma; (2) giant
cells MFH/undifferentiated pleomorphic sarcoma;
Epidemiology and localization. Epithelioid
(3) MFH/undifferentiated pleomorphic sarcoma
hemangioendothelioma is a rare tumor that has
with prominent inflammation.
been described in the soft tissues of the limbs,
usually occurring inside a medium-sized vein, in Epidemiology. Undifferentiated pleomorphic sar-
the lungs (originally considered as an intravascu- coma was by far the most frequent primary car-
lar bronchioalveolar tumor) and in the liver, diac malignancy (about 50%) in the past [31], but
where it seems to be related to oral contraceptive actually, thanks to the use of immunohistochem-
use. Only a few cases have been reported in the istry, it is a diagnosis by exclusion when all the
heart, located close to atrio-ventricular sulcus immunohistochemical stains fail to give evidence
[26] or in the valves [27]. of specific differentiation and it is very rare
Gross features. It consists grossly of small, red- [32–34]. The Atlas of Armed Force Institute of
dish nodules with frequent calcifications. Pathology [2] reports still a high frequency of
these tumors (24% of all cardiac sarcomas), but
Histopathological features. It is characterized by this is due to the unavailability of material for
round or oval cells, arranged in short strands and immunohistochemical/ultrastructural analysis in
nests; these cells present with small intracellular most cases.
lumina, which mimic the vacuoles observed in
some cells of adenocarcinoma. The expression Localization. Most undifferentiated sarcomas
of vascular endothelial markers, such as factor arise in the left atrium (posterior wall and/or inter-
VIII, CD31, and CD34, by cells of epithelioid atrial septum), and have an intracavitary growth,
hemangioendothelioma, rules out metastatic mimicking cardiac myxoma [35] (Fig. 6.2a).
adenocarcinoma.
Clinical presentation. Patients with MFH/undif-
A chromosomal translocation involving chro-
ferentiated sarcomas present with constitutional
mosomes 1 and 3 has been detected by cytoge-
or obstructive symptoms, including pulmonary
netic analysis in 2 out of 3 cases of soft tissue
congestion, mitral valve obstruction, dyspnea,
epithelioid hemangioendothelioma [28, 29].
chest pain, congestive heart failure, or arrhyth-
Prognosis. The occurrence of systemic metasta- mias. Metastasis to the lymph nodes, lungs, skin,
ses has been described in 10% of the extra-cardiac and systemic organs occurs early.
cases. Cardiac epithelioid hemangio-endothe- Echocardiography is helpful in demonstrating
lioma can produce systemic metastases. In the a cardiac mass, but CT and MRI are required to
medical literature only a case of epithelioid assess local extent or metastases for preoperative
hemangioendothelioma originating from the heart planning when curative management is contem-
with systemic metastases has been reported [30]. plated and postoperatively to identify if excision
Fig. 6.2 Left atrial malignant fibrous histiocytoma in a surgical resected mass showed a rough and irregular sur-
68 -year-old man, presenting with fever and increased face. (c) At histology, bizarre cells with pleomorphic
serum inflammatory markers. Reprinted with permission nuclei admixed to giant cells and spindle-shaped cells,
of the Italian Society of Cardiology. (a) Two-dimensional with high mitotic rate are seen (hematoxylin–eosin stain).
echocardiography: an endoluminal round mass is visible (d) At immunohistochemistry, the tumor cells are positive
in the left atrium, simulating a myxoma. (b) Grossly, the to vimentin
is complete and tumor recurrence in the (endothelial, cardiomyocytes, smooth muscle

follow-up. cells, fibroblasts, adipose, nerves, epithelial cells).
Histogenesis of tumor cells is still debated; a his-
Gross features. Tumor may appear as a yellow-
tiocytic origin has been suggested due to immu-
ish–white polypoid mass, pedunculated or ses-
nostaining positive for a1 antichymotrypsin,
sile, with areas of necrosis and hemorrhage
complement receptors, and Ig [37], but the histio-
(Fig. 6.2b). Unlike cardiac myxoma, it may pres-
cytic markers, including CD15 and CD14, are
ent as multiple intracavitary cardiac masses [36].
negative.
Histopathological features. MFH/undifferenti- Genetic alterations, in particular in chromo-
ated pleomorphic sarcoma is characterized by a some 13, have been reported in soft tissue sarco-
proliferation of bizarre spindle-shaped or epithe- mas MFH [38–40], but cytogenetic analysis on
lioid cells with pleomorphic nuclei, often admixed cardiac tumors is still lacking.
with giant cells in a storiform pattern. Mitotic The prognosis of cardiac MFH is very poor,
figures are usually abundant (Fig. 6.2c, d). The because surgical resection is often incomplete.
tumor is diagnosed as a pleomorphic MFH/undif- Chemotherapy and radiotherapy give only
ferentiated pleomorphic sarcoma when histology temporary improvement. Heart or heart/lung
and immunohistochemistry fail to give evidence transplantation [8, 35, 41, 42] as well as auto-
of myogenic or other specific differentiation transplantation [43] might be an alternative.
Fig. 6.3 Fibrosarcoma of the right atrium in a 62 -year-old panoramic view of bioptic specimens (hematoxylin–eosin
woman, suffering from weakness and effort dyspnea. stain). (c) At higher magnification, note atypical spindle
Reprinted with permission of the Italian Society of cells within a fibrous stroma (hematoxylin–eosin stain).
Cardiology. (a) CT showing a mass infiltrating the right (d) At immunohistochemistry, the tumor cells are positive
atrial free wall. (b) Transvenous endomyocardial biopsy: for vimentin
Survival of patients ranges from 5 [2] to tary and mural (Fig. 6.3a) growth; congestive heart
18 months [35]. Most patients ultimately die of failure due to pulmonary congestion and mitral
metastasis or local recurrence. stenosis are the most common clinical presentations.
Heterologous elements such as bone are More rarely, it originates from the pericardium.
identi fi ed in 15% of MFH. In the past these vari-
Gross features. It is usually a soft, lobulated,
ants were diagnosed as primary cardiac osteosar-
polypoid mass projecting into the cardiac
comas, which are almost invariably located in the
chamber.
left atrium [44, 45]; only a case has been described
in the right ventricle [46]. Histopathological features. Fibrosarcoma is com-
posed of monomorphic spindle cells, with variable
mitotic activity (Fig. 6.3b-d) arranged in fascicles
with a storiform, “herring-bone”pattern within a
Fibrosarcoma and Myxosarcoma
collagen stroma. Immunohistochemically, the
tumor cells are positive for vimentin and focally
Cardiac fibrosarcoma consists of a malignant pro-
for a-smooth muscle actin [48]. Ultrastructural
liferation of mesenchymal cells with fibroblastic
examination reveals features of fibroblasts (spindle
features [1, 2, 47].
morphology and prominent rough endoplasmic
Epidemiology, localization, and clinical presenta- reticulum) or myofibroblasts (spindle morphology
tion. These rare tumors represent about 5–10% of and prominent rough endoplasmic reticulum
cardiac sarcomas. The most frequent location is in together with focal presence of basal lamina,
the atria (particularly the left), with both intracavi- myofilaments, and “dense bodies”).
Prognosis. In spite of surgery, survival is poor, stains, it was thought to be the most common pri-
about 5 months [2]. mary cardiac sarcoma; nowadays, it is considered
According to the WHO classification [1], very rare, accounting for around 5% of primary
myxosarcoma is the myxoid variant of cardiac malignancies. Probably it is still the most com-
fibrosarcoma, showing ovoid or stellate-shaped mon sarcoma in children [49]. Recently, Donsbech
cells enmeshed within a myxoid stroma. Neither et al. [50] revalued 24 tumors by immunohis-
cellular pleomorphism nor prominent vascular tochemistry previously diagnosed as rhabdomyo-
component is present in fibrosarcoma and in sarcomas by simple histological stains; the
myxofibrosarcoma. diagnosis was not confirmed in any case.
In the past, myxosarcoma was thought to be Noteworthy, no rhabdomyosarcoma has been
the malignant transformation of myxoma [48]. reported among Mayo Clinic cases [51].
Nowadays, it is considered the equivalent to the Cardiac rhabdomyosarcomas typically involve
extracardiac soft tissue myxo-fibrosarcoma and the myocardium and show no chamber predilec-
fibromyxoid sarcoma at a low grade of malig- tion, although they more often occur in the ven-
nancy, which are grouped among fibroblastic/ tricles than other type of sarcomas.
myofibroblastic neoplasms [2].
Gross features. These tumors are large, bulky,
infiltrative masses, either gelatinous or soft and
necrotic (Fig. 6.4) and rarely present with an
Rhabdomyosarcoma
endocavitary growth [52].
Rhabdomyosarcoma is a malignant mesenchy- Histopathological features. In soft tissues, rhab-
mal tumor with striated muscle differentiation. In domyosarcoma is divided into three subtypes,
the past, before the use of immunohistochemical i.e., embryonal (including botryoid variant),
Fig. 6.4 Rhabdomyosarcoma in

a 36- year-old patient at autopsy.
Reprinted with permission of the
Italian Society of Cardiology.
(a) Chest X-ray shows pericardial
and right pleural effusion.
(b) At ECG, atrio-ventricular
dissociation is present.
(c) At autopsy, the tumor appears
as a bulky mass infiltrating the
left atrial posterior wall.
(d) At histology, tumor cells
appear pleomorphic and
tadpole-like, with small transverse
bands in the cytoplasm
(hematoxylin–eosin stain)

alveolar, and pleomorphic. Primary cardiac rhab- Leiomyosarcoma

domyosarcomas are virtually all of the embryo-
nal subtype. In the heart the botryoid variant has Leiomyosarcoma is a malignant mesenchymal
been reported only in two cases [53, 54] and the tumor with smooth muscle differentiation.
alveolar subtype only as metastatic [55].
Epidemiology. Leiomyosarcoma represents about
Embryonal rhabdomyosarcoma is composed of
10% of primary cardiac sarcomas, usually affect-
small-sized round cells with hyperchromic nuclei
ing patients during the fourth decade [1, 2], with-
and high mitotic rate, and rhabdomyoblasts with
out any sex predilection.
eosinophilic and PAS positive cytoplasm,
described as “tadpole cells” (Fig. 6.4d). The more Localization. There are two usual sites of origin.
the myoblasts, the greater the differentiation. One is the left atrium, where it may present as a
Positive nuclear immunostaining with anti- single or multinodular endocavitary mass, mim-
bodies to myogenin [56] and positive cytoplas- icking the left atrial myxoma, although it is
mic staining with antibodies to desmin allow the mostly attached to the posterior wall and infiltrates
diagnosis. the pulmonary veins [59] (fig 6.5). The second
Sarcoma botryoid is a multilobated grape-like location is the pulmonary infundibulum and
mass, histologically showing cambium layer cells artery, where it may present abruptly to mimic
in a myxomatous stroma. pulmonary embolism (Fig. 6.6) [1, 2].
Electron microscopy reveals thin and thick
filaments and structure resembling Z lines. Gross features. It appears like a gray–white, solid
Cytogenetic analysis shows mutation in exon 1 of sessile, intraluminal mass (Fig. 6.5a, b). In 30%
K-ras gene [57]. of cases tumor may present as multiple nodules.
Treatment. Surgical resection is often palliative Histopathological features. Leiomyosarcoma con-

due to local and distant metastasis, and response sists of compacted fascicles of spindle cells with
to adjuvant radiation and chemotherapy is dis- blunt-ended nuclei and eosinophilic cytoplasm
mal. In selected cases, cardiac transplantation has (Figs. 6.5c and 6.6b), containing glycogen and peri-
been even considered [58]. nuclear vacuoles. There are areas of necrosis and high
mitotic activity. The spindle cells show positive
Fig. 6.5 Leiomyosarcoma of the left atrium in a 21-year- whitish, lardaceous appearance. (c) At histology, pleo-
old woman with acute pulmonary edema and a preopera- morphic cells arranged in a storiform pattern within a
tive diagnosis of left atrial myxoma. Reprinted with myxoid background (hematoxylin–eosin stain). (d)
permission of the Italian Society of Cardiology. (a) Gross Immunohistochemical staining showing tumor cells posi-
features of the mass resected at surgery, showing a rough tivity for desmin
and irregular surface. (b) Cut-surface of the mass with a
Fig. 6.6 Leiomyosarcoma of the pulmonary artery surgi- (b) At higher magnification, compact bundles of spindled
cally resected in a 53-year-old woman. Reprinted with cells with blunt-ended nuclei were seen (hematoxylin–
permission of the Italian Society of Cardiology. (a) eosin stain). (c) Immunohistochemical positivity of tumor
Histological picture showing the pulmonary artery cells for smooth muscle actin. (d) Immunohistochemical
occluded by a neoplastic lesion (hematoxylin–eosin stain). positivity of tumor cells for desmin
reactivity for a-smooth muscle actin (Fig. 6.6c) of only a uniform spindle cell component. The
and desmin (Fig. 6.5d and 6.6d). presence of edema between bundles of spindle
cells allows the differential diagnosis with
Prognosis. Surgical resection, usually associated
fibrosarcoma.
with adjuvant chemotherapy and radiation, is
Immunohistochemical staining shows that the
considered palliative, and the mean survival time
spindle cells are diffusely positive for vimentin,
being about 1 year. Nevertheless, one case sur-
and also focally positive for a-smooth muscle
vived more than 7 years after surgical resection
actin and calretinin; instead, epithelioid compo-
and radio/chemotherapy, one patient underwent
nent is positive for cytokeratins and epithelial
to cardiac transplantation after tumor eradication
membrane antigen (EMA). The cells are negative
by chemotherapy, and finally a 21 -year-old
for CD34, and this feature in association with
patient was still alive 24 months after the diagno-
dense cellular distribution and high grade malig-
sis has been reported [60].
nancy helps to distinguish this tumor from soli-
tary fibrous tumor of the pericardium. Differential
diagnosis includes also sarcomatoid malignant
Synovial Sarcoma mesothelioma that grossly proliferates diffusely
and covers the surface of the heart; moreover,
Synovial sarcoma is a malignant tumor which synovial sarcoma histologically is composed of
most commonly arises in the soft tissue near the more uniform tumor cells. Detection of SS18-
joints of the arm and leg, but may be found in SSX(SYT-SSX) or t(X; 18)(p11.2; q11.2) chro-
many organs, including the heart. mosomal translocation by molecular genetic
Because this characteristic location near the analysis using reverse transcription polymerase
joints and the microscopic similarity to synovia, chain reaction (RT-PCR), performed also in
in the past it was erroneously thought to have a paraffin-embedded tissue blocks [62, 63], is
synovial origin. It is a biphasic tumor composed extremely useful for reaching a definitive diagno-
of two kinds of cells, spindle-shaped and epithe- sis of synovial sarcoma.
lioid cells; monomorphic variant, composed only
by spindle-shaped cells may occur and is the vari-
ant more frequently described in the heart. In all Liposarcoma
cases a reciprocal translocation t(x; 18)(p11.2;
q11.2) is present. Liposarcoma is a mesenchymal malignant tumor
In the literature, 14 cases of synovial sarcoma that contains lipoblasts.
have been reported that originated in the heart or In the literature, about 20 cases have been
pericardium. The patients’ age range is reported [64]. Liposarcoma usually develops in
13–53 years [61]. adulthood, arises in the atria, and has an endolu-
There is a predilection for the atria and minal growth, simulating cardiac myxoma [65],
pericardial surfaces. Clinically, patients present but may involve also the pericardium causing
symptoms related to intracardiac obstruction, effusion or cardiac tamponade [2, 66].
embolism, or cardiac tamponade.
Gross features. On gross examination liposarco-
Gross features. The tumor is whitish, infiltrative, mas are generally yellowish masses, sometimes
and accompanied by necrosis and hemorrhage. myxoid, flaccid, and multilobulated [2].
Histopathological features. Synovial sarcomas Histopathological features. Two main subtypes
are classified into a biphasic type, which is arise in the heart: pleomorphic liposarcoma, sim-
composed of a spindle cell component and an ulating malignant fibrous histiocytoma, and myx-
epithelial cell component, proliferating in a oid liposarcoma.
nodular or glandular fashion; and a monophasic The histological hallmark of liposarcoma is
type, the most common in the heart, consisting lipoblast, the precursor cell for adipocytes, which
in the pleomorphic subtype presents with centrally

located nucleus and multiple cytoplasmic small Cardiac Lymphoma
lipid droplets, while in the myxoid subtype it
appears as a cell containing a unique large lipid Primary cardiac lymphoma (PCL) is an extra-
droplet, which displaces the nucleus giving the cell nodal non-Hodgkin’s lymphoma exclusively
a signet ring shape. In addition a plexiform capillary located in the heart and/or pericardium.
pattern and a myxoid matrix are present. Mixed Primary cardiac lymphomas are very rare, rep-
forms have been described. Immunohistochemical resenting 1.3% of primary cardiac tumors [2,
staining shows S100 positivity in tumor cells. At 67–69].
electron microscopic examination, lipid droplets They may occur in both immunodeficient and
do not exhibit a discrete membrane. immunocompetent people. The median age of
patients with PCL is 62 years (range 5–90), and it
occurs three times more frequently in men than in
Sarcomas Not Included in the WHO women. The prognosis is poor with median sur-
Classification vival of 7 months.
Initial signs and symptoms include shortness
Malignant mesenchymoma is defined as a malig- of breath, palpitations, chest pain, syncope,
nant tumor that consists of two or more different arrhythmia, congestive heart failure, or pericar-
mesenchymal components in addition to poorly dial effusion.
differentiated mesenchymal cells, as seen in
Gross features. It presents as a whitish intramural
MFH/undifferentiated pleomorphic sarcoma.
infiltrating mass which may involve also the peri-
“Triton’s tumors” are rare, malignant tumor made
cardium causing massive effusion. The right
up of both malignant schwannoma cells and
atrium is the most common site of origin (two
malignant rhabdomyoblasts.
third of cases), but any chamber may be
Malignant peripheral nerve sheath tumor
involved.
(MPNST), also called neurofibrosarcoma or
malignant schwannoma, is a malignant tumor Histopathological features. Almost 80% of PCLs
composed of spindle cells, irregular nuclei, are diffuse large B-cell lymphomas (Fig. 6.7)
arranged in a plexiform pattern and positive for which at immunohistochemistry reveal expres-
S100 at immunohistochemistry. sion of CD45 and of the B-cell marker CD20
Malignant rhabdoid tumor is characterized (Fig. 6.7d), whereas the remaining 20% are CD3
ultrastructurally by perinuclear prominent inter- positive T-cell lymphomas.
mediate filaments, positive for vimentin. In the Immunocompromised HIV-positive individu-
WHO classification [1] it is considered as a sub- als and patients affected by Kaposi sarcoma may
type of MFH/undifferentiated pleomorphic sar- develop so-called “primary effusion lymphoma”
coma, which sometimes shows similar cells. (PEL), that is pericardial effusion without the
Kaposi’s sarcoma has been described in the evidence of neoplastic mass, in which large
heart as a multifocal tumor in immunocompro- B-cells present with co-infection by HHV-8/
mised patients [2]. KSHV and EBV.
Carcinosarcoma is a high grade malignancy Cytology of pericardial effusion and molecu-
composed of epithelial and mesenchymal cells, lar techniques may be of help for diagnosis to dif-
showing features of both rhabdomyosarcoma and ferentiate B and T-cell lymphomas from reactive
adenocarcinoma [3]. lymphocyte hyperplasia.
Fig. 6.7 Primary cardiac lymphoma in a 36- year-old (b) Border area between the neoplastic infiltration and
man, drug abuser and HIV infected, with echocardio- normal myocardium (hematoxylin–eosin stain). (c) At
graphic finding of a mass infiltrating the right atrial free higher magnification, the tumor cells are large with large
wall. Reprinted with permission of the Italian Society of nuclei (hematoxylin–eosin stain). (d) At immunohistohe-
Cardiology. (a) The myocardium is diffusely infiltrated by mistry, tumor cells are positive for CD20, a B-cell marker
proliferating neoplastic cells (hematoxylin–eosin stain).
Primary Malignant Tumors of the Malignant mesothelioma. Primary pericardial

Pericardium malignant mesothelioma arises from the pericardial
mesothelial cell layer. It is a rare tumor, account-
Solitary fibrous tumor. This is a rare spindle cell ing for only about 1% of all mesotheliomas.
tumor that occurs most commonly in the pleura, Mesothelioma development has been correlated
where is known as benign mesothelioma, although with exposure to asbestos or after direct application
may be present also in other locations such as the of asbestos and fiber glass as a treatment for angina
pericardium [70–72]. pectoris [73, 74], and with radiation therapy for
Grossly, the tumor is firm, well circumscribed. breast and mediastinal malignancies [75]. It affects
Histologically spindle cell or hemangiopericy- individuals of any age (mean 45 years). Clinical
toma-like patterns are observed and fibrous or manifestations are hemorrhagic pericardial effu-
myxoid areas may be present. The neoplastic sion, constrictive pericarditis or, more rarely,
cells are CD34 positive [72]. The differential cardiac tamponade [76].
diagnosis includes malignant mesothelioma, low Imaging techniques such as MRI and CT can
grade fibrosarcoma, and monophasic synovial be helpful to achieve diagnosis, identifying the
sarcoma: immunohistochemical stain with CD34 pericardial thickening or the pericardial mass and
is vital in identifying solitary fibrous tumor. the effusion.
Prognosis is good, but local recurrence has Grossly, pericardial mesothelioma may pres-
been reported. ent as nodules which may become confluent
Fig. 6.8 Primary malignant mesothelioma of the pericar- shows the whitish mass encasing both ventricles. (b) At
dium in a 47- year-old man presenting with pericardial histology, tumor cells form characteristic tubulo-papillary
effusion. Reprinted with permission of the Italian Society structures (hematoxylin–eosin stain)
of Cardiology. (a) At autopsy, transverse cut of the heart
encasing the heart and the root of the great ves- The outcome is poor, with a median life expec-
sels (Fig. 6.8). tancy very low, approximately 6 months from
Histologically, the tumor cells may have two diagnosis.
distinct patterns i.e., epithelioid, with papillary or
Germ cell tumors. The intrapericardial germ cell
tubular configuration, or sarcomatoid. Immuno-
tumors are generally benign teratomas. Pathologic
histochemistry shows calretinin and cytokeratin
evaluation may reveal areas of malignant degen-
5/6 positivity and CEA negativity, at difference
eration with features of a yolk sac tumor [77]
from metastatic adenocarcinoma. Presence of
secreting alpha-fetoprotein [78]. The prognosis
cell microvilli at electron microscopy is also
depends upon the extension of these malignant
diagnostic [2].
areas.
Yolk sac tumor rarely involves the pericar- cardiac tumors: review of a single institution experi-
dium; a true “Yolk sac tumor” of the pericardium ence. Cancer. 2008;112:2440–6.
14. Mayer F, Aebert H, Rudert M, Königsrainer A, Horger
has been reported only in one case [79]. M, Kanz L, Bamberg M, Ziemer G, Hartmann JT.
Primary malignant sarcomas of the heart and great
vessels in adult patients–a single-center experience.
References Oncologist. 2007;12:1134–42.
15. Glancy DL, Morales Jr JB, Roberts WC. Angiosarcoma
of the heart. Am J Cardiol. 1968;21:413–9.
1. Trawis WD, Brambilla E, Muller-Hermelink HK, 16. Rosenkranz ER, Murphy Jr DJ. Diagnosis and neona-
Harris CC, editors. World Health Organization tal resection of right atrial angiosarcoma. Ann Thorac
classification of tumors: pathology and genetics of Surg. 1994;57:1014–5.
tumours of the lung, pleura, thymus and heart. Lyon: 17. Adem C, Aubry MC, Tazelaar HD, Myers JL.
IARC Press; 2004. p. 250. Metastatic angiosarcoma masquerading as diffuse
2. Burke AP, Virmani R. Tumors of the heart and great pulmonary hemorrhage: clinicopathologic analysis of
vessels. 3rd ed. Washington, DC: Armed Forces 7 new patients. Arch Pathol Lab Med.
Institute of Pathology; 1996. 2001;125:1562–5.
3. Ramnarine IR, Davidson L, van Doorn CA. Primary 18. Afzal MN, Alguacil-Garcia A. Primary cardiac
cardiac carcinosarcoma: a rare, aggressive tumor. Ann angiosarcoma: clinical and pathological diagnostic
Thorac Surg. 2001;72:927–9. problems. Can J Cardiol. 1997;13:293–6.
4. Fletcher CDM, Unni KK, Mertens F. World Health 19. Poletti A, Cocco P, Valente M, Fasoli G, Chioin R,
Organization classification of tumors: tumours of soft Thiene G. In vivo diagnosis of cardiac angiosarcoma
tissue and bone. Lyon: IARC Press; 2002. by endomyocardial biopsy. Cardiovasc Pathol.
5. Costa J. The grading and staging of soft tissue sarco- 1993;2:89–91.
mas. In: Fletcher CD, McKee PH, editors. Pathobiology 20. Araoz PA, Mulvagh SL, Tazelaar HD, Julsrud PR,
of soft tissue tumors. Edinburg: Churchill Livingstone; Breen JF. CT and MR imaging of benign primary car-
1990. p. 221–38. diac neoplasms with echocardiographic correlation.
6. Trojani M, Contesso G, Coindre JM, Rouesse J, Bui Radiographics. 2000;20:1303–19.
NB, de Mascarel A, Goussot JF, David M, Bonichon 21. Economides EG, Singh A. Case of tumor neovascu-
F, Lagarde C. Soft tissue sarcomas of the adults; study larization demonstrated by cardiac catheterization.
of pathological prognostic variables and definition of Cathet Cardiovasc Diagn. 1998;43:451–3.
a histopathological grading system. Int J Cancer. 22. Garcia JM, Gonzalez R, Silva JM, Dominguez G,
1984;33:37–42. Vegazo IS, Gamallo C, Provencio M, Espana P,
7. Coindre JM, Terrier P, Gouillou L, Le Doussal V, Bonilla F. Mutational status of K-ras and TP53 genes
Collin F, Ranchere D, Sastre X, Vilain MO, Bonichon in primary sarcomas of the heart. Br J Cancer.
F, N’Guiyen Bui B. Predictive value of grade for 2000;82:1183–5.
metastasis development in the main histologic types 23. Zu Y, Perle MA, Yan Z, Liu J, Kumar A, Waisman J.
of adult soft tissue sarcomas: a study of 1240 patients Chromosomal abnormalities and p53 gene mutation a
from the French Federation of Cancer Centers cardiac angiosarcoma. Appl Immunohistochem Mol
Sarcoma Group. Cancer. 2001;91:1914–26. Morphol. 2001;9:24–8.
8. Uberfuhr P, Meiser B, Fuchs A, Schulze C, 24. Kim MP, Correa AM, Blackmon S, Quiroga-Garza G,
Reichenspurner H, Falk M, Weiss M, Wintersperger Weilbaecher D, Bruckner B, Ramlawi B, Rice DC,
B, Issels R, Reichart B. Heart transplantation: an Vaporciyan AA, Reardon MJ. Outcomes after right-
approach to treating primary cardiac sarcoma? J Heart side heart sarcoma resection. Ann Thorac Surg.
Lung Transplant. 2002;21:1135–9. 2011;91:770–6.
9. Reardon MJ, Walkes JC, Benjamin R. Therapy 25. Hermann MA, Shankerman RA, Edwards WD, Shub
insight: malignant primary cardiac tumors. Nat Rev C, Schass HV. Primary cardiac angiosarcoma: a clini-
Cardiol. 2006;3:548–53. copathologic study of six cases. J Thorac Cardiovasc
10. Butany J, Yu W. Cardiac angiosarcoma: two cases and Surg. 1992;103:655–64.
a review of the literature. Can Cardiol. 26. Burke AP, Tazelaar H, Butany JW, EI-Demellawy D,
2000;16:197–205. Loire R, Geva T, Bonilla F, Galvin JR, Veinot JP,
11. Hamidi M, Moody JS, Weigel TL, Kozak KR. Primary Virmani R, Kamiya H, Watanabe G, Grandmougin
cardiac sarcoma. Ann Thorac Surg. 2010;90:176–81. D, Horimoto M, Hiraga H. Cardiac sarcomas. In:
12. Yu K, Liu Y, Wang H, Hu S, Long C. Epidemiological Trawis WD, Brambilla E, Muller-Hermelink HK,
and pathological characteristics of cardiac tumors: a Harris CC, editors. World Health Organization
clinical study of 242 cases. Interact Cardiovasc Thorac classification of tumors: pathology and genetics of
Surg. 2007;6:636–9. tumours of the lung pleura thymus and heart. Lyon:
13. Simpson L, Kumar SK, Okuno SH, Schaff HV, Porrata IARC Press; 2004. p. 273–81.
LF, Buckner JC, Moynihan TJ. Malignant primary
27. Van Bernal JF, Garcia Alberdi E, Gutierrez JA, Garijo 42. Talbot SN, Taub RN, Keohan ML, Edwards N,
MF. Incidental in vivo detection of an epitheliod Galantowicz ME, Schulman LL. Combined heart and
hemangioendothelioma of the mitral valve. Pathol Int. lung transplantation for unresectable primary cardiac
2005;55:644–8. sarcoma. J Thorac Cardiovasc Surg.
28. Boudousquie AC, Lawce HJ, Sherman R, Olson S, 2002;124:1145–8.
Magenis RE, Corless CL. Complex translocation (7; 43. Reardon MJ, De Felice CA, Sheinbaum R, Baldwin
22) identified in an epithelioid hemangioendothe- JC. Cardiac autotransplant for surgical treatment of a
lioma. Cancer Genetic Cytogenet. 1996;92:116–21. malignant neoplasm. Ann Thorac Surg.
29. Mendlick MR, Nelson M, Pickering D, Johansson SL, 1999;67:1793–5.
Seemayer TA, Neff JR, Vergara G, Rosenthal H, 44. Reynard JS, Gregoratos G, Gordon MJ, Bloor CM.
Bridge JA. Translocation t(1; 3)(p36.3; q25) is a non- Primary osteosarcoma of the heart. Am Heart J.
random aberration in epithelioid hemangioendothe- 1985;109:598–600.
lioma. Am J Surg Pathol. 2001;25:684–7. 45. Burke A, Virmani R. Osteosarcomas of the heart. Am
30. Marchiano D, Fisher F, Hofstetter S. Epithelioid J Surg Pathol. 1991;15:289–95.
hemangioendothelioma of the heart with distant 46. Yamagishi M, Bando K, Furuichi S, Ishibashi-Ueda
metastases: A case report and literature review. H, Yutani C, Miyatake K. Images in cardiovascular
J Cardiovasc Surg. 1993;34:529–33. medicine: primary cardiac osteosarcoma in right ven-
31. Whorton CM. Primary malignant tumors of the heart. tricular outflow tract. Circulation. 2000;101:2220–1.
Cancer. 1949;2:245–60. 47. Basso C, Stefani A, Calabrese F, Fasoli G, Valente M.
32. Bear PA, Moodie DS. Malignant primary cardiac Primary right atrial fibrosarcoma diagnosed by endo-
tumors. The Cleveland Clinic experience, 1956 to cardial biopsy. Am Heart J. 1996;131:399–402.
1986. Chest. 1987;92:860–2. 48. Okada M, Ohta T, Yasuoka S, Matsuda S, Shida T,
33. Molina JE, Edwards JE, Ward HB. Primary cardiac Nakamura K, Asada S. Surgical management of intra-
tumors: experience at the University of Minnesota. cavitary tumors. A review of fifteen patients and cur-
Thorac Cardiovasc Surg. 1990;38:183–91. rent status in Japan. J Cardiovasc Surg.
34. Basso C, Valente M, Poletti A, Casarotto D, Thiene G. 1986;27:641–9.
Surgical pathology of primary cardiac and pericardial 49. Hui KS, Green LK, Schmidt WA. Primary cardiac
tumors. Eur J Cardiothorac Surg. 1997;12:730–7. rhabdomyosarcoma: definition of a rare entity. Am J
35. Okamoto K, Kato S, Katsuki S, Wada Y, Toyozumi Y, Cardiovasc Pathol. 1988;2:19–29.
Morimatsu M, Aoyagi S, Imaizumi T. Malignant 50. Donsbeck AV, Ranchere D, Coindre JM, Le Gall F,
fibrous histiocytoma of the heart: case report and Cordier JF, Loire R. Primary cardiac sarcomas: an
review of 46 cases in the literature. Intern Med. immunohistochemical and grading study with long-
2001;40:1222–6. term follow-up of 24 cases. Histopathology.
36. Laya MB, Mailliard JA, Bewtra C, Levin HS. 1999;34:295–304.
Malignant fibrous histiocytoma of the heart. A case 51. Tazelaar HD, Locke TJ, McGregor CG. Pathology of
report and review of the literature. Cancer. surgically excised primary cardiac tumors. Mayo Clin
1987;59:1026–31. Proc. 1992;67:957–65.
37. Terashima K, Aoyama K, Nihei K, Nito T, Imai Y, 52. Thiene G, Miraglia G, Menghetti L, Nava A, Rossi L.
Takahashi K, Daidoji S. Malignant fibrous histiocy- Multiple lesions of the conduction system in a case of
toma of the heart. Cancer. 1983;52:1919–26. cardiac rhabdomyosarcoma with complex arrhyth-
38. Mairal A, Terrier P, Chibon F, Sastre X, Lecesne A, mias. An anatomic and clinical study. Chest.
Aurias A. Loss of chromosome 13 is the most fre- 1976;70:378–81.
quent genomic imbalance in malignant fibrous histio- 53. Hajar R, Roberts WC, Folger Jr GM. Embryonal
cytoma. A comparative genomic hybridization botryoid rhabdomyosarcoma of the mitral valve. Am
analysis of a series of 30 cases. Cancer Genet J Cardiol. 1986;57:376.
Cytogenet. 1999;111:134–8. 54. Scott RS, Jagirdar J. Right atrial botryoid rhabdomyo-
39. Chibon F, Mairal A, Freneaux P, Terrier P, Coindre sarcoma in an adult patient with recurrent pleomor-
JM, Sastre X, Aurias A. The RB1 gene is the target of phic rhabdomyosarcomas following doxorubicin
chromosome 13 deletions in malignant fibrous histio- therapy. Ann Diagn Pathol. 2007;11:274–6.
cytoma. Cancer Res. 2000;60:6339–45. 55. Orsmond GS, Knight L, Dehner LP, Nicoloff DM,
40. Simons A, Schepens M, Jeuken J, Sprenger S, van de Nesbitt M, Bessinger Jr FB. Alveolar rhabdomyosar-
Zande G, Bjerkehagen B, Forus A, Weibolt V, coma involving the heart. An echocardiographic,
Molenaar I, van den Berg E, Myklebost O, Bridge J, angiographic and pathologic study. Circulation.
van Kessel AG, Suijkerbuijk R. Frequent loss of 9p21 1976;54:837–43.
(P16(INK4A)) and other genomic imbalances in 56. Quintanilla-Martinez L, Wilkins Jr EW, Choi N, Efird
human malignant fibrous histiocytoma. Cancer Genet J, Hug E, Harris NL. Thymoma. Histologic subclas-
Cytogenet. 2000;118:89–98. sication is an independent prognostic factor. Cancer.
41. Gowdamarajan A, Michler RE. Therapy for primary 1994;74:606–17.
cardiac tumors: is there a role for heart transplanta- 57. Garcia JM, Gonzalez R, Silva JM, Dominguez G,
tion? Curr Opin Cardiol. 2000;15:121–5. Vegazo IS, Gamallo C, Provencio M, Espana P, Bonilla
F. Mutational status of K-ras and TP53 genes in primary cardiac tamponade and multiple organ metastates
sarcomas of the heart. Br J Cancer. 2000;82:1183–5. (Letter). Chest. 1993;103:328.
58. Grandmougin D, Fayad G, Decoene C, Pol A, 67. Cairns P, Butany J, Fulop J, Ralowski H, Hassaram S.
Warembourg H. Total orthotopic heart transplantation Cardiac presentation of non-Hodgkin’s lymphoma.
for primary cardiac rhabdomyosarcoma: factors Arch Pathol Lab Med. 1987;111:80–3.
influencing long-term survival. Ann Thorac Surg. 68. Petrich A, Cho SI, Billett H. Primary cardiac
2001;71:1438–41. lymphoma: an analysis of presentation, treatment, and
59. Mazzola A, Spano JP, Valente M, Gregoriani R, outcome patterns. Cancer. 2011;117:581–9.
Villani C, Di Eusanio M, Ciocca M, Minuti U, 69. Rolla G, Bertero MT, Pastena G, Tartaglia N, Corradi
Giancola R, Basso C, Thiene G. Leiomyosarcoma of F, Casabona R, Motta M, Caligaris-cappio F. Primary
the left atrium mimicking a left atrial myxoma. lymphoma of the heart. A case report and review of
J Thorac Cardiovasc Surg. 2006;131:224–6. the literature. Leuk Res. 2002;26:117–20.
60. Pessotto R, Silvestre G, Luciani GB, Anselmi M, Pasini 70. Bortolotti U, Calabro F, Loy M, Fasoli G, Altavilla G,
F, Santini F, Mazzucco A. Primary cardiac leiomyosar- Marchese D. Giant intrapericardial solitary fibrous
coma: seven-year survival with combined surgical and tumor. Ann Thorac Surg. 1992;54:1219–20.
adjuvant therapy. Int J Cardiol. 1997;60:91–4. 71. Corgnati G, Drago S, Bonamini R, Trevi GP, Carra R,
61. Hazelbag HM, Szuhai K, Tanke HJ, Rosenberg C, Di Summa M. Solitary fibrous tumor of the pericar-
Hogendoorn PC. Primary synovial sarcoma of the dium presenting itself as a pericardial effusion and
heart: a cytogenetic and molecular genetic analysis right ventricular obstruction. J Cardiovasc Surg.
combining RT-PCR and COBRA-FISH of a case with 2004;45:393–4.
a complex karyotype. Mod Pathol. 2004;17:1434–9. 72. Hanau CA, Miettinen M. Solitary fibrous tumor: his-
62. Guillou L, Coindre JM, Bonichon F, Nguyen BB, tological and immunohistochemical spectrum of
Terrier P, Collin F, Vilain MO, Mandard AM, le Doussal benign and malignant variants presenting at different
V, Benhattar J. Detection of the synovial sarcoma trans- sites. Hum Pathol. 1995;26:440–9.
location t(X;18) (SYT; SSX) in paraffin-embedded 73. Krismann M, Muller KM. Malignant mesothelioma
tissues using reverse transcriptase-polymerase chain of the pleura, pericardium and peritoneum. 1:
reaction. A reliable and powerful diagnostic tool for Etiology, pathogenesis, pathology. Chirurg. 2000;
pathologists. A molecular analysis of 221 mesenchy- 71:877–86.
mal tumors fixed in different fixatives. Hum Pathol. 74. Churg A, Warnock ML, Bensch KG. Malignant meso-
2001;32:105–12. thelioma arising after direct application of asbestos
63. Amary MF, Berisha F, Bernardi Fdel C, Herbert A, and fiber glass to the pericardium. Am Rev Respir
James M, Reis-Filho JS, Fisher C, Nicholson AG, Dis. 1978;118:419–24.
Tirabosco R, Diss TC, Flanagan AM. Detection of 75. Small GR, Nicolson M, Buchan K. Pericardial malig-
SS18-SSX fusion transcripts in formalin-fixed nant mesothelioma: a latent complication of radio-
paraffin-embedded neoplasms: analysis of conven- therapy? Eur J Cardiothor Sur. 2008;33:745–7.
tional RT-PCR, qRT-PCR and dual color FISH as 76. Loire R, Tabib A. Malignant mesothelioma of the
diagnostic tools for synovial sarcoma. Mod Pathol. pericardium. An anatomo-clinical study of 10 cases.
2007;20:482–96. Arch Mal Coeur Vaiss. 1994;87:255–62.
64. Paraf F, Bruneval P, Balaton A, Deloche A, Mikol J, 77. McKenney H. Congenital teratomas. Am J Surg
Maitre F, Scholl JM, De Saint-Maur PP, Camilleri JP. Pathol. 2005;29:29–38.
Primary liposarcoma of the heart. Am J Cardiovac 78. Carachi R, Campbell PE, Chow CW, Mee BB. Alpha-
Pathol. 1990;3:175–80. feto-protein-(AFP-)-secreting intra-pericardial tera-
65. Nzayinambaho K, Noel H, Cosyns J, Sonnet J, Chalant toma–report of a case diagnosed on CT scanning. Z
C. Primary cardiac liposarcoma simulating a left atrial Kinderchir. 1986;41:369–70.
myxoma. Thorac Cardiovasc Surg. 1985;33:193–5. 79. Liang TC, Lu MY, Chen SJ, Lu FL, Lin KH. Cardiac
66. Can C, Arpaci F, Celasum B, Gunham O, Finci R. tamponade caused by intrapericardial yolk sac tumor
Primary pericardial liposarcoma presenting with in a boy. J Formos Med Assoc. 2002;101:355–8.
Echocardiographic Approach to
the Diagnosis of Cardiac Tumors 7
Paolo Voci and Francesco Pizzuto
ence, which is particularly true for small and

Introduction unusual lesions. The cardiologist performing
the examination should know the clinical his-
Before the clinical introduction of echocardiog- tory of the patient and should be expert on the
raphy, the in vivo diagnosis of cardiac tumors wide spectrum of cardiac masses which may be
was virtually impossible, and almost exclusively incidentally encountered during a routine
done at autopsy [1]. examination.
Echocardiography has definitely changed Very often cardiac tumors are asymptomatic
the diagnostic work-up of cardiac tumors, at an early stage, and in about 12% of the cases
allowing an easy, early, fast, low-cost, and they are occasionally found during ultrasound
accurate diagnosis [2–12]. As a result, the prog- examination requested for other reasons [13].
nosis improved too. In fact, before the introduc- They often produce mild clinical signs, but some-
tion of echocardiography the prognosis was times their first clinical presentation is dramatic
poor not only for malignant, but also for benign with life-threatening arrhythmias, atrioventricu-
neoplasms, such as myxomas, fibromas, and lar block, pericardial effusion or tamponade, car-
fibroelastomas, which could not be recognized diac failure [14], severe valvular regurgitation,
until progressive obstruction of cardiac cham- pulmonary hypertension secondary to left ven-
bers, severe arrhythmias, and/or embolic events tricular inflow obstruction, and embolic events.
occurred. Sometimes general signs as fever and artralgia
The ultrasound diagnosis of cardiac tumors may also occur [15].
depends on the technological level of the instru-
mentation and on the operator’s skill and experi-
Prevalence
P. Voci, M.D. (*) Primary cardiac tumors are much rarer than
Department of Internal Medicine, metastatic tumors (prevalence at autopsy of
Section of Cardiology, Tor Vergata University, 0.001–0.28% and 1.5–21%, respectively) [16–18].
Viale Oxford 81, Via Merulana 13, Rome 00185, Italy
e-mail: paolovoci@gmail.com
The “3/4 rule” may be a useful mnemonic aid:
more than 3/4 of primary tumors are benign and
F. Pizzuto, M.D.
Department of Internal Medicine,
3/4 of those are atrial myxomas, which therefore
Section of Cardiology, Tor Vergata University, are the most common cardiac tumors; 3/4 of
Viale Oxford 81, Via Nomentana 186, Rome 00185, Italy malignant cardiac tumors are sarcomas [19].

92 P. Voci and F. Pizzuto
Fig. 7.1 Transesophageal echocardiography. Reprinted with permission of the Italian Society of Cardiology. Large left
atrial myxoma attached to the interatrial septum, prolapsing in diastole through the mitral valve
How to Distinguish a Malignant from

a Benign Lesion
The histological differentiation of cardiac masses

or even the ability to simply distinguish between
a malignant and a benign mass is still very
difficult with ultrasound, and sometimes even at
surgical inspection. Therefore, the histological
diagnosis at surgery is deemed necessary to make
a correct and definitive diagnosis and to optimize
therapy. Despite these important limitations,
some ultrasound characteristics as the number of
masses, their location, their ultrasound texture,
and the presence of calcification, may help sug- Fig. 7.2 Fetal echocardiography. Reprinted with permis-
gesting the histological type. sion of the Italian Society of Cardiology. Large right
ventricular fibroma (T) occasionally seen in a fetus
Number. Myxomas are the most frequent cardiac without signs of heart failure
tumors. They are usually made of a single intrac-
ardiac mass (Fig. 7.1) but very rarely, and partic-
ularly in young patients, they are multiple. growth of a small mass, therefore, this criterion
Fibromas are made of a single mass too, but they may have a limited value.
are usually found well before the adolescence
Location. Myxomas are generally found in the
when compared to myxomas, and sometimes,
atria, particularly in the left atrium, and almost
albeit very rarely, even in utero (Fig. 7.2).
always originate from the atrial septum (Fig. 7.1),
Rhabdomyomas are often multiple (Figs. 7.3 and
whereas rarely involve the valvular or subvalvu-
7.4), they are associated with tuberous sclerosis,
lar apparatus [10]. They are almost never found
and may regress spontaneously.
on the posterior wall of the left atrium, which
Dimensions. Fibromas are usually very large may help differentiating them from atrial thrombi
(Fig. 7.2) whereas rhabdomyomas are of variable or leiomyosarcomas. Fibroelastomas are almost
dimensions (Figs. 7.3 and 7.4), but most often always attached to a cardiac valve, mostly to the
small, and may regress spontaneously. aortic valve (Fig. 7.5), then to the mitral valve
Fibroelastoma is usually small (Fig. 7.5) and and very rarely the tricuspid valve and the endo-
other tumors may be very different in size. cardial wall. Rhabdomyomas have a typical
Obviously, a big mass always derives from the intramyocardial distribution. Lipomas are found
7 Echocardiographic Approach to the Diagnosis of Cardiac Tumors 93
Fig. 7.3 Neonatal echocardiography. Reprinted with atrium in a newborn with heart failure, confirmed at
permission of the Italian Society of Cardiology. Two autopsy. AO aorta, LA left atrium, LV left ventricle, RA
rhabdomyomas, the smaller at the apical segment of the right atrium, RV right ventricle, RVOT right ventricular
interventricular septum (arrow) and the larger in the left outflow tract
Fig. 7.5 Color-Doppler transthoracic echocardiography.

Fibroelastoma of the aortic valve (arrow)
Ultrasound structure. The ultrasound “texture”

Fig. 7.4 Two-dimensional echocardiography. Reprinted
with permission of the Italian Society of Cardiology. Left
and some peculiar characteristics of cardiac
ventricular short-axis view in a 12-year-old child with tuber- tumors may help in the differential diagnosis.
ous sclerosis. Arrows indicate rhabdomyomas in regression Teratomas and hamartomas are often non-homo-
geneous and may have spotty calcifications,
in the interatrial septum, they are round or they whereas rhabdomyomas are homogeneous
may produce a diffuse septal infiltration known (Figs. 7.3 and 7.4). Left atrial thrombi can be dif-
as septal lipomatosis, but they may be observed ferentiated from myxomas when a multi-layered
in other structures, included the pericardium. structure is detected. Echo-lucent or transparent
Sarcomas (Figs. 7.6 and 7.7) may be found in any areas, corresponding to hemorrhagic or necrotic
part of the heart. spots at histology, may be also be detected in
myxomas, (Fig. 7.1) but exceptionally in vegeta- chromocytoma independently from its ability to
tions and thrombi. Lipomas are homogeneous produce catecholamines, is an exception. In this
and markedly hyper-reflective masses. tumor, which is most often benign, the vascular-
ization is so developed (Fig. 7.8) that coronary
Vascularization. A rich vascularization may sug-
steal and even angina may occur [12]. Cardiac
gest the diagnosis of malignancy. However, the
hemangioma, which is benign too, is also highly
paraganglioma, which is also called cardiac pheo-
vascularized [5]. Lastly, the presence of vessels
in a cardiac mass is not typical of tumors: in fact,
old thrombi may be perfused by neovessels which
can be imaged by high-resolution ultrasound
(Fig. 7.9) [20].
Cardiac myxoma, the great mimic. The case of
myxoma demonstrates how many exceptions
may have these diagnostic tips. The cardiac myx-
oma is a mobile mass attached to the left side of
the fossa ovalis by a peduncle allowing wide back
and forth excursion in the left atrial chamber. The
mass may obstruct in diastole the atrioventricular
inflow (Fig. 7.1) thus clinically mimicking mitral
stenosis, and similar to mitral stenosis it may pro-
duce embolic events secondary to fragmentation
of the fragile mass. In 10% of the cases the mass
is sessile.
The site of attachment, dimensions, and struc-
ture of myxomas may be very heterogeneous. In
the large study of Goswami et al. [3] 84% origi-
Fig. 7.6 Transthoracic echocardiography. Reprinted with nated from the left atrium, 12% from the right
permission of the Italian Society of Cardiology. Short-
atrium, and the remaining 4% from both atria.
axis view at the level of the great arteries. Sarcoma
infiltrating the right ventricular outflow tract and the pul- Sixty-nine percent of left atrial myxoma origi-
monary artery nated from the fossa ovalis, 28% from the inferior
Fig. 7.7 Transthoracic echocardiography. Large sarcoma infiltrating the anteroseptal and apical wall of both left and
right ventricles, with massive pericardial effusion
Fig. 7.8 Transthoracic color-Doppler echocardiography. Reprinted with permission of the Italian Society of Cardiology.
Richly vascularized right atrial paraganglioma
border of the septum, and the remaining 3% from Which Role for Transesophageal
the lateral wall. Similarly, the great majority of Echocardiography?
right atrial myxomas originated from the right
side of the fossa ovalis. All biatrial myxomas in Transthoracic echocardiography has greatly
this large series straddled the fossa ovalis. Very improved in the last decade allowing better detec-
rarely myxomas may be found in both the right tion of structures in the far field, as the atria. In a
and left ventricle. The surface is most often recent review of 149 primary cardiac tumors in
smooth and globular, but in 15% of the cases it China [1] transthoracic echocardiography was
may be papillary and friable. Echo-lucent areas diagnostic in 93.3% of the cases. In the 10
within the myxoma can be found in 70% of the remaining cases missed at transthoracic echocar-
cases, often as large as 1 cm [2]. In about 10% of diography the mass was in the pericardium (eight
the cases, calcifications may be also observed. cases), in the left atrium (one case), and on the
When the diagnosis is made in a young patient, posterior surface of the heart (one case).
one should always consider the presence of mul- Of course, transesophageal echocardiogra-
tiple and relapsing lesions and a familiar phy [5–8] has a better resolution than transtho-
distribution. racic echocardiography, because the acoustic
Fig. 7.9 Transthoracic color-Doppler echocardiography. Doppler tracing with the characteristic anterograde sys-
Vascularized apical thrombus. Upper panel: epicardial tolic and diastolic flow. Lower panel: vascularized apical
tract of the left anterior descending (LAD) coronary artery thrombus with flow directed away from the transducer
visualized by color-Doppler and the corresponding pulsed (modified from Voci et al. [20])
impedance is lower and the transducers have a Lastly, transesophageal echocardiography moni-
higher spatial resolution. Despite this advan- tors weaning from cardiopulmonary bypass, par-
tage, transesophageal echocardiography not ticularly patients undergoing partial ventricular
often brings additional information over transt- resection for infiltrating tumors. Sometimes
horacic echocardiography, relevant for surgical transesophageal echocardiography may help
referral of the patient [3]. However, the supe- guiding transvenous biopsy of right chamber
rior wall of the right atrium and the right atrial masses particularly of inoperable malignant
appendage are only incompletely seen by tumors, when the histology is necessary to guide
transthoracic echocardiography and anatomi- chemotherapy.
cal details of the inferior and superior vena
cava may be better seen by transesophageal
echocardiography [7]. Metastatic tumors
Intraoperative transesophageal echocardiog-
raphy is useful to guide surgery and to evaluate The prevalence of cardiac metastasis from tumors
the results of valve repair in case of infiltration of originated in the lung, breast, kidney, skin, and
the atrioventricular valves or to confirm the colon is 100–1,000 times higher compared to
absence of intracardiac shunts after septal repair. primary cardiac tumors [1]. Cardiac metastases
represent a social problem, because paradoxi- patients also increased the prevalence of cardiac
cally the improvement in chemo- and radiother- metastasis, from 0.2 to 6% before 1996 to more
apy, prolonging the life expectancy of these than 10% in 2003 [2]. Cardiac metastases can be
intramyocardial (Fig. 7.10) and/or pericardial
(Fig. 7.11) and produce pericardial effusion and
tamponade. Lymphoma may compress the car-
diac chambers (Fig. 7.12) or produce the superior
vena cava syndrome (Fig. 7.13). Kidney tumors
may infiltrate the inferior vena cava and reach the
right atrium (Fig. 7.14), even causing pulmonary
neoplastic embolism.
Conclusions
Nowadays, the diagnosis of cardiac tumors is

based mainly on transthoracic echocardiography
which allows to visualize a cardiac mass and to
roughly predict its nature. Transesophageal
Fig. 7.10 Two-dimensional echocardiography, apical echocardiography is indicated in the rare cases
four-chamber projection. Reprinted with permission of
the Italian Society of Cardiology. Metastatic melanoma
when transthoracic echocardiography is non-
infiltrating almost entirely the right ventricle, and prolaps- diagnostic, and in the perioperative monitoring of
ing in systole through the tricuspid valve complex lesions.
Fig. 7.11 Two-dimensional echocardiography. Pericardial attached to the parietal pericardium and does not infiltrate
metastasis secondary to a colon carcinoma. The off-axis the myocardium, being therefore suitable for surgical
projection in the right panel clearly shows that the mass is resection
Fig. 7.12 Mediastinal lymphoma compressing the left atrium (LA). LV left ventricle
Fig. 7.13 Intrathoracic lymphoma (CT scan, right panel) leading to superior vena cava syndrome with marked stagna-
tion of flow in the jugular vein (left panel)
Fig. 7.14 Right kidney tumor producing a mobile mass in the inferior vena cava (upper panel) and right atrial metas-
tasis (lower panel)
3. Goswami K, Shirivasta S, Bahl VK, Saxena A,

References Manchanda SC, Wasir HS. Cardiac myxomas: clinical
and echocardiographic profile. Int J Cardiol.
1. Meng Q, Lai H, Lima J, Tong W, Qian Y, Lai S. 1998;63:251–9.
Echocardiographic and pathologic characteristics of 4. Padalino MA, Basso C, Svaluto Moreolo G, Thiene
primary cardiac tumors: a study of 149 cases. Int J G, Stellin G. Left atrial myxoma in a child. Case
Cardiol. 2002;84:69–75. report and review of the literature. Cardiovasc Pathol.
2. Butany J, Nair V, Naszemuddin A, Nair GM, Cotton 2003;12:233–6.
C, Yau T. Cardiac tumors: diagnosis and treatment. 5. Rizzoli G, Bottio T, Pittarello D, Napodano M, Thiene
Lancet Oncol. 2005;6:219–28. G, Basso C. Atrial septal mass: transesophageal
echocardiographic assessment. J Thorac Cardiovasc Kirklin JK, McGiffin DC, Pacifico AD. Live three-
Surg. 2004;128:767–9. dimensional transthoracic echocardiographic assess-
6. Perez de Isla L, De Castro R, Zamorano JL, Almeria ment of left atrial tumors. Echocardiography.
C, Moreno R, Moreno M, Lima P, Garcia Fernandez 2005;22:137–43.
MA. Diagnosis and treatment of cardiac myxomas by 12. Turley AJ, Hunter S, Stewart M. A cardiac paragan-
transesophageal echocardiography. Am J Cardiol. glioma presenting with atypical chest pain. Eur J
2002;90:1419–21. Cardiothorac Surg. 2005;28:352–4.
7. Leibowitz G, Keller NM, Daniel WG, Freedberg RS, 13. Reynen K. Cardiac myxoma. N Engl J Med.
Tunica PA, Stottmeister C, Kronzon I. Transesophageal 1995;333:1610–7.
versus transthoracic echocardiography in the evaluation 14. Salcedo EE, Cohen GL, White RD, Davison M.
of right atrial tumors. Am Heart J. 1995;130:1224–7. Cardiac tumors: diagnosis and management. Curr
8. Mahdhaoui A, Bouraoui H, Amine MM, Mokni M, Probl Cardiol. 1992;17:73–137.
Besma T, Ernez Hajri S, Deridi G, Khelfa M, Bahri F, 15. Pinede L, Duhaut P, Loire R. Clinical presentation of
Yacoubi T, Sriha B, Ammar H. The transesophageal left atrial cardiac myxoma. A series of 112 consecu-
echocardiographic diagnosis of left atrial myxoma tive cases. Medicine. 2001;80:159–72.
simulating a left atrial thrombus in the setting of mitral 16. Glancy DL, Roberts WC. The heart in malignant mel-
stenosis. Echocardiography. 2004;21:233–6. anoma. A study of 70 autopsy cases. Am J Cardiol.
9. Vieira MLC, Ianni BM, Mady C, Encinas J, 1968;2:355–71.
Pommerantzeff PMA, Fernandes PP, Leal SB, Mathias 17. Centofanti P, Di Rosa E, Deorsola L. Primary cardiac
Jr W, Andrade JL, Ramires JA. Left atrial myxoma. tumors: early and late results of surgical treatment in
Three-dimensional echocardiographic assessment. 91 patients. Ann Thorac Surg. 1999;68:1236–41.
Arq Bras Cardiol. 2004;82:284–6. 18. Silverman NA. Primary cardiac tumors. Ann Surg.
10. Borges AC, Witt C, Bartel T, Muller S, Konertz W, 1980;191:127–38.
Baumann G. Preoparative two- and three-dimensional 19. Vander Salm TJ. Unusual primary tumors of the heart.
transesophageal echocardiographic assessment of Semin Thorac Cardiovasc Surg. 2000;12:89–100.
heart tumors. Ann Thorac Surg. 1996;61:1163–7. 20. Voci P, Pizzuto F, Romeo F. Coronary flow: a new
11. Mehmood F, Nanda NC, Vengala S, Winokur T, Dod asset for the echo lab? Eur Heart J. 2004;25:1867–79.
HS, Ebenezer F, Patel V, Bodiwala K, Upendram S,
Echocardiography of
Cardiac Masses: From Two- 8
to Three-Dimensional Imaging
Luigi P. Badano, Denisa Muraru, and Sabino Iliceto
[3], but a lower detection rate for pericardial or

Introduction paracardiac lesions. Although cardiac tumors can
often be seen by two-dimensional transthoracic
Tumors involving the heart can cause symptoms echocardiography, their location, size, and relation-
and signs due to obstruction of cardiac chambers ships with surrounding structures are better defined
and great vessels, pulmonary or systemic embo- by transesophageal echocardiography.
lization, complete heart block and arrhythmias, or Visualizing the suspected cardiac mass through-
cardiac tamponade, although they are often also out the cardiac cycle in more than one view, with
incidental findings. In the past, they were often the appropriate transducer and scanner settings, are
discovered at autopsy. Nowadays, technologic important rules for the proper characterization of
advances in cardiovascular imaging have led to a the mass, avoiding the misinterpretation of arti-
substantial increase in antemortem diagnoses. facts. A thorough knowledge of normal anatomy,
Echocardiography is the imaging technique of physiologic variants, and embryonic remnants, as
choice to detect intracardiac masses in the clinical well as familiarity with structural changes associ-
practice [1, 2]. This tool has the unique advantage ated with various operative and interventional pro-
of being able to provide a non-invasive dynamic cedures are crucial and will decrease the likelihood
assessment of cardiac masses, to evaluate their of misdiagnosis. Finally, it is pivotal that clinical
hemodynamic impact and the presence of associ- and personal information are available at the time
ated abnormalities (Table 8.1). However, current of the study, to be used for interpreting echocardio-
echocardiographic techniques do not allow tissue graphic findings in context.
characterization. In this chapter, we will focus on Conventional (i.e., two-dimensional)
the echocardiographic characteristics of primary echocardiography is a tomographic technique,
and secondary cardiac tumors. and effective interpretation of images requires
Both transthoracic and transesophageal echocar- one to mentally integrate them into a three-
diography have shown a good sensitivity to detect dimensional (3D), stereoscopic reconstruction
intracardiac tumors (93.3 and 96.8%, respectively, of the heart. For example, an intracardiac tumor
in one series of pathologically confirmed tumors) may have quite variable site of attachment,
shape, and size, requiring the echocardiographer
to examine the tumor from a series of two-
L.P. Badano, M.D. (*) • D. Muraru, M.D. • S. Iliceto, M.D. dimensional images and then to “mentally”
Cardiology, Department of Cardiac, Thoracic and reconstruct the tumor to define its size, shape,
Vascular Sciences, University of Padua
Medical School, Via N. Giustiniani 2,
and attachment. To do this accurately, a clini-
Padua 35128, Italy cian should understand the relationship of each
e-mail: lpbadano@gmail.com two-dimensional tomographic image to one
102 L.P. Badano et al.
Table 8.1 Echocardiographic assessment of cardiac masses

Characterization of the mass
Location Intra- or extracardiac
Relationship with adjacent
structures
Site, mobility, and mode of
implantation
Route of access to the heart Superior/inferior vena cava
Pulmonary veins
Uncertain
Shape and size (3D volume) Largest diameters or maximal area
Hemodynamic/functional Obstruction and/or regurgitation by interfering with valve function
consequences Extracardiac compression
Segmental wall motion abnormalities or restrictive disease due to direct
infiltration of the myocardium
Pericardial infiltration and/or effusion with variable degree of hemodynamic
impairment
Vascularization Contrast
Differential diagnosis
Benign
1. Embryonic remnants Chiari network, Eustachian valve, etc.
2. Thrombi Free-floating or attached (mural, device or catheter-related)
3. Benign cardiac tumors
4. Vegetations
Malignant
1. Primary
2. Metastatic
Fig. 8.1 Atypical left atrial myxoma. (a) At two-dimen- dimensional echocardiography confirms the attachment of
sional echocardiography, a large mass is seen attached by a the mass to the left atrial free wall and shows no interference
short stalk (white arrow) to the left atrial free wall. Echodensity with mitral valve (MV) function. (c) Three-dimensional
is not homogeneous; echolucencies within the mass represent echocardiography showing the shape of the mass, its volume,
hemorrhagic areas. A myxoma has been diagnosed at surgical and irregular surface. Mitral valve is seen in the background.
inspection and then proven at histology. (b) Color flow two- Ao aortic valve, LV left ventricle, MV mitral valve
8 Echocardiography of Cardiac Masses: From Two- to Three-Dimensional Imaging 103
Fig. 8.2 Right atrial myxoma. (a) A large, not homoge- of contrast agent suggesting a poorly vascularized mass
neous and mobile mass (arrow) attached to the interatrial (courtesy of Agata Barchitta, M.D., Ospedale CTO S
septum is visualized in the right atrium. (b). Partial Antonio, ULSS 16, Padova, Italy). LA left atrium, LV left
enhancement of the mass tissue after intravenous injection ventricle, RV right ventricle
another. 3D echocardiography eliminates the surrounding myocardium, suggesting a poorly

need for cognitive reconstruction of image vascularized mass such as myxoma (Fig. 8.2); and
planes and use of geometric assumptions about complete enhancement with higher intensity than
the shape of structures for quantitation. This adjacent myocardium, suggesting a highly vascu-
particularly applies to complex shapes such as larized tumor which is a characteristic of rapidly
intracardiac tumors (Fig. 8.1) [4–6]. Once a 3D growing malignant tumors.
data set is acquired, it can be cropped and sliced
in many different ways. In addition, the possi-
bility of rotating the data sets in the space allows Myxoma
the observer to obtain planes and views and to
align structures in ways that were impossible to Myxomas can cause obstruction and/or regurgi-
achieve with conventional two-dimensional tation by interfering with valve function and
echocardiography. Thus, additional information frequently embolize, so that their immediate
about mass location, shape, attaching interface, removal after diagnosis is mandatory.
and relationships with adjacent structures can Myxomas are usually solitary and are located
be derived from 3D data sets [7]. most frequently (approximately 75% of the
Contrast echocardiography is another echo cases) in the left atrium (Fig. 8.1), with the
modality which may be used to detect cardiac remainder largely arising within the right atrium
masses (i.e., in patients with inadequate acoustic (Fig. 8.3a). Myxomas arising from the ventricles,
window) and/or to differentiate among various mitral valve, as well as multiple myxomas
types of cardiac masses [8, 9]. Three different echo (Fig. 8.3b) within the same cardiac chamber
contrast patterns can be seen in intracardiac masses, have also been exceptionally described.
i.e., no enhancement at all by the contrast agent, Therefore, a careful transesophageal echocardio-
suggesting the presence of thrombi since they are graphic study should be conducted preopera-
generally avascular; partial enhancement with tively to be sure that all tumors have been
decreased pixel intensity in comparison with the detected and will be removed.
Fig. 8.3 (a) A large right atrial myxoma attached to inter- septum, associated with a second smaller mass attached to the
atrial septum. Areas of calcification (arrow) and echolucencies left side of interatrial septum (arrow), that were found to be
(dashed arrow) can be appreciated within this polypoid mass. myxomas at pathological examination. LA left atrium,
(b) A large right atrial mass (arrow) attached to the interatrial LV left ventricle, RA right atrium, RV right ventricle
The typical atrial myxoma manifests as a sin- be qualitatively assessed by color Doppler flow
gle intracardiac homogeneous or finely speckled imaging and measured by continuous-wave
compact, rounded, or ovoid mass mass, isodense Doppler sampling of the ventricular inflow which
to the surrounding myocardium, attached to the will show, in case of significant obstruction, the
interatrial septum near the fossa ovalis by a stalk- typical tracing morphology of functional mitral
like pedicle. However, echocardiographic appear- (or tricuspid, in case of right atrial myxoma)
ance can be also that of a polypoid, papillary, stenosis.
friable mass attached to the endocardium of any Although transthoracic two-dimensional
cardiac structure. Size can vary from less than 1 echocardiography has been found to be highly
cm to an extent that virtually fills the whole accurate in providing all relevant information
atrium. The echogenity of myxomas may not be for surgery [8], transesophageal echocardiogra-
homogeneous, since they frequently contain cys- phy has a higher sensitivity in detecting myxomas
tic spaces, and areas of necrosis, hemorrhage, in comparison with transthoracic echocardiogra-
and calcification. Inhomogeneous appearance is phy, especially in the setting of small myxomas,
useful to differentiate them from large thrombi. and should be performed in any case with the
Mobility of myxoma depends on its size and the suspicion of intracardiac tumor or unknown
type of attachment; however, prolapsing of the source of embolism. Transesophageal echocar-
tumor into the ventricles through the atrio-ven- diography, particularly 3D modality, is also use-
tricular valves is a common characteristic of atrial ful in very large myxomas nearly filling the
myxomas. The attachment may be broad and atrial chamber, in close contact with large areas
hence they may also appear as immobile or hypo- of atrial endocardium throughout the cardiac
mobile masses. The degree of functional obstruc- cycle, in which the stalk cannot be clearly
tion to ventricular filling caused by the tumor can visualized.
Fig. 8.4 Lipomatous

hypertrophy of the
interatrial septum.
Transesophageal echocar-
diography shows the
typical thickening of the
interatrial septum (Lip)
that spares the region of
the fossa ovalis (arrow)
giving the classic dumbbell
appearance to the
interatrial septum (courtesy
of Pasquale Gianfagna,
M.D., Cardiothoracic
Department, Azienda
Ospedaliero-Universitaria,
Udine, Italy). IVC inferior
vena cava, LA left atrium,
RA right atrium
Postoperative echocardiography should be transverse dimension (Fig. 8.4) [11]. It is asso-

performed to document the complete excision of ciated with advanced age and obesity and
the tumor. Since recurrent myxomas have been caused by an increase in the number of adipo-
reported, long-term follow-up is indicated, par- cytes. Lipomatous hypertrophy of interatrial
ticularly in the familial form of the disease. septum typically spares the fossa ovalis (giv-
ing rise to the characteristic “dumbbell” shape
to the interatrial septum) and does not repre-
Cardiac Lipoma and Lipomatous sent a true cardiac tumor [11]. In rare cases, an
Hypertrophy of Interatrial Septum obstruction of inferior vena cava may occur.
Lipomas are encapsulated, hyperdense, homoge-

neous tumors which can be found throughout the Papillary Fibroelastoma
heart, typically in subepicardial or subendocardial
location. Rarely, they can arise within the myo- Papillary fibroelastomas are the most common
cardium or from the valve leaflets. Occasionally, tumors of the cardiac valves. Echocardio-
they may grow as broad-based, pedunculated graphically, they manifest as small (2–10 mm),
masses into any of the cardiac chambers and may usually single, mobile, pedunculated echo masses
reach giant sizes and weigh up to 4.8 kg [10]. which can be filamentous, frond-like, or oval in
Usually, there is no calcification, necrosis, or shape, typically attached to the valve leaflets on
intratumoral hemorrhage, as opposed to myxo- either side of the heart. Due to their small size,
mas. Intrapericardial lipomas may cause com- papillary fibrobroelastomas could not be detected
pression of the heart and pericardial effusion. by transthoracic echocardiography.
Lipomatous hypertrophy of interatrial sep- Ninety percent of papillary fibroelastomas
tum has often been included in reports of car- occur on valve surfaces, being more commonly
diac lipomas. Lipomatous hypertrophy of found on the aortic valve (29%, where they can
interatrial septum is defined as any deposit of arise from both surface, Fig. 8.5) and on the
fat in the atrial septum which exceeds 2 cm in mitral valve (25%, mainly arising from the atrial
Fig. 8.5 Papillary

fibroelastoma of the aortic
valve. Transesophageal
echocardiogram revealed a
small, oval-shaped, highly
mobile mass (arrow)
attached to the body of the
right coronary cusp of the
aortic valve by a short stalk
(courtesy of Pasquale
Gianfagna, M.D.,
Cardiothoracic
Department, Azienda
Ospedaliero-Universitaria,
Udine, Italy). Ao aorta, LA
left atrium, LVOT left
ventricular outflow tract
Fig. 8.6 Papillary fibroelastoma of the mitral valve. (a) portion of the leaflet and a better appreciation of its mor-
Transesophageal echocardiogram showed a large, highly phology and size (courtesy of Pasquale Gianfagna, M.D.,
mobile mass on the ventricular side of the anterior mitral Cardiothoracic Department, Azienda Ospedaliero-
valve leaflet (arrow). (b) Three-dimensional echocardiog- Universitaria, Udine, Italy). LA left atrium, LV left ventri-
raphy allowed the localization of this mass at the mid cle, RV right ventricle
side, Fig. 8.6), than on the pulmonary (13%) or Papillary fibroelastomas often appear like
tricuspid valves (17%) [12]. Sixteen percent of infectious vegetations or Lambl’s excrescences,
papillary fibroelastomas have been reported to which makes differential diagnosis difficult. Large
arise from nonvalvular surfaces (Fig. 8.7) and mobile vegetations attached to the valves may
from the subvalvular apparatus of the mitral mimic papillary fibroelastomas, but the clinical
valve [13]. context suggestive of infective endocarditis helps
Fig. 8.7 Uncommon

localization of papillary
fibroelastoma on the
endocardium of the
interventricular septum.
Transthoracic two-dimen-
sional echocardiography,
zoomed apical five-
chamber view: a frond-
like, highly mobile mass is
attached to the left
ventricular endocardium in
the outflow tract (arrow).
The mass was resected and
found to be a fibroelastoma
(courtesy of Pasquale
Gianfagna, M.D.,
Cardiothoracic
Department, Azienda
Ospedaliero-
Universitaria,Udine, Italy).
Ao aortic valve, LV left
ventricle, LA left atrium,
RV right ventricle
in differentiating between them. Lambl’s excres- tumors are usually located in the myocardium of
cences, which can be found as normal features in both ventricles and multiplicity is common
many adults, are filamentous, mobile, and avascu- (Fig. 8.8), but intracavitary growths can be found
lar structures that generally arise at the closure line in more than 50% of patients. They may also origi-
of the valves [14]. Papillary fibroelastomas are not nate within the atrium or in the atrio-ventricular
as thin as Lambl’s excrescences and, unlike the lat- junction. When occurring intramural, they appear
ter, they do not arise from the leaflet closure line, as bright intramural masses with luminal exten-
but from other regions on the valve surface. sion. A circumscribed ventricular wall thickening
Fibroelastomas may also be confused with blood of the left and/or right ventricle can be detected.
cysts, which are unusual, blood-containing, cystic When intracavitary, rhabdomyomas will more fre-
structures that develop within atrio-ventricular quently appear as echodense structures, lobulated
valve leaflets. Blood cysts are sessile with a broader in shape and ventricular in origin. They may be
base, and thus less mobile than fibroelastomas. associated with mechanical complications, such as
outflow tract obstruction. Multifocal lesions are
common.
Rhabdomyoma Since regression of these tumors with com-
plete resolution during infancy is expected in
Rhabdomyomas are the most common primary more than 80% of cases, surgery is indicated only
cardiac tumor in children and up to 50% of them in the setting of severe symptoms and signs and
are associated with tuberous sclerosis. These echocardiography is the technique of choice to
Fig. 8.8 Rhabdomyoma in a child with tuberous sclero- ventricular lateral wall (dashed arrow) (courtesy of
sis. Transthoracic apical four-chamber view showing a Pasquale Gianfagna, M.D., Cardiothoracic Department,
large, lobulated, and echodense mass localized at the left Azienda Ospedaliero-Universitaria, Udine, Italy). LA left
atrio-ventricular junction (arrow). A smaller mass can be atrium, LV left ventricle, RA right atrium, RV right
seen within the myocardium of the apical region of the left ventricle
monitor the hemodynamic significance of the Hemangioma

tumor and its evolution.
Hemangiomas can occur in any cardiac location and
can arise from endocardium, myocardium, epicar-
Fibroma dium, or pericardium (Fig. 8.9a). Hemangiomas are
typically intramyocardial, although most often involve
Echocardiographic appearance of cardiac fibroma the base of the heart. They appear as hyperreflective
is that of a single intramural (typically occurring (but not calcific) masses varying in size (between 1
in the interventricular septum, less frequently in and 8 cm) and are usually associated with pericardial
the left ventricular free wall) hyperechogenic, effusion. The vascularized nature of this tumor is
noncontractile mass [15]. It may be confused difficult to be appreciated on conventional echocar-
with asymmetric hypertrophic cardiomyopathy diography. After contrast injection, the tumor is com-
or infiltrative myocardial disease, but usually its pletely enhanced (Fig. 8.9b), showing a greater
abnormal texture helps in reaching the correct intensity than the surrounding myocardium [9, 17].
diagnosis. The size of the mass may vary consid-
erably, from 1 up to 10 cm. A pathognomonic
echocardiographic feature of large fibromas is Teratoma
the presence of calcifications due to poor blood
supply. Strain rate can be used to confirm the Intracardiac location of teratomas is very rare. They
noncontractile nature of the mass [16]. In addi- are usually located within the pericardial space,
tion to its detection, echocardiography is useful with a non-homogeneous echogenity and multicys-
to monitor the growth of the tumor and, postop- tic appearance and may present as a large hemoperi-
eratively, to check for its recurrence. cardium causing hemodynamic compromise [18].
Fig. 8.9 A rare hemangioma of the interatrial septum. the tumor highlighting the infiltration of the interatrial
(a) Two-dimensional four-chamber apical view show- septum (dashed arrow). The three-dimensional data
ing a large mass infiltrating the interatrial septum set allows a better appreciation of the shape of the
(arrow). (b) Complete enhancement of the mass tissue mass, its volume, and its relationship with interatrial
(arrow) with higher intensity than adjacent myocar- septum (dashed arrow) and right atrial walls (Courtesy
dium after intravenous injection of contrast agent, sug- of Agata Barchitta, M.D., Ospedale CTO S Antonio,
gesting a highly vascularized tumor. (c and d) ULSS 16, Padova, Italy). LA left atrium, LV left ven-
Transesophageal two- and three-dimensional image of tricle, RA right atrium, RV right ventricle
entiate between benign myxomas and

Sarcoma malignant angiosarcomas, is the evidence of
in fi ltration of the cardiac wall and of the peri-
Ninety-five percent of primary malignant cardium. Sarcomas may cause hemodynamic
tumors are sarcomas. Among these, angiosar- compromise as a result of obstruction any-
coma is the most frequent and, despite it can where in the right heart in fl ow or out fl ow
arise in any part of the heart, its most frequent tract. Angiosarcoma appears as a large, broad-
location is the right atrium. The main echocar- based, mobile, inhomogeneous mass with
diographic characteristic, that helps to differ- hypodense necrotic and hemorrhagic zones
Fig. 8.10 Undifferentiated primary cardiac sarcoma of mass (arrow) protruding into the left ventricular cavity.
the left ventricle (localized at the apex and infiltrating left (b) Magnetic resonance imaging, four-chamber view,
ventricular wall). The large size of the mass seen in this showing the mass infiltrating the left ventricular myocar-
patient is not unusual for this tumor type, given its rapid dium of the distal part of interventricular septum and apex
and aggressive growth pattern. (a) Apical five-chamber (arrow). LV left ventricle, RV right ventricle
view of the left ventricle showing an apical large polypoid
and a “cauliflower” shape. In fi ltration of the within the mass can be differentiated from
pericardium, tricuspid valve, and vena cava angiosarcomas.
can be frequently visualized. In the setting of Infusion of contrast can help in differentiating
a hemorrhagic pericardial effusion, a benign from malignant tumors. Highly vascular
malignant tumor should be always consid- tumors like sarcomas become visually hyperen-
ered [19 ]. hanced and demonstrate quantitatively more per-
Undifferentiated sarcoma (Fig. 8.10), malig- fusion than the adjacent myocardium [17].
nant fibrous histiocytoma, leiomyosarcoma,
rhabdomyosarcoma, osteosarcoma, fibrosarcoma,
and liposarcoma are rare primary malignant Lymphoma
cardiac tumors. Echocardiographic characteris-
tics of the other cardiac sarcomas are similar to Primary cardiac lymphomas are defined as non-
those listed for angiosarcomas, except they are Hodgkin lymphomas involving only the heart/
not characteristically located within the right pericardium or as non-Hodgkin lymphomas with
atrium, but elsewhere in the heart, predominantly the bulk of the tumor located in the heart [20].
within the left atrium. In the latter situation, they They are very rare in immunocompetent patients
often originate from the roof of the left atrium or [21]. Their incidence is rising with the increasing
non-septal structures and this serves as a criterion prevalence of patients with AIDS or heart trans-
of discrimination from myxomas. They appear as plant. At echocardiographic examination, lym-
large, mobile, and inhomogeneous masses with phomas commonly arise in the right atrium and
zones of necrosis and hemorrhage and are appear as large, immobile, sometimes polypoid
indistinguishable from angiosarcoma. Only oste- masses (Fig. 8.11) [22]. They frequently coexist
osarcomas which show typical calcifications with pericardial effusion.
Fig. 8.11 Primary cardiac lymphoma in the right rior vena cava at transesophageal echocardiography
atrium. (a) At transesophageal echocardiography, a showing the extension of the tumor within the supe-
large mass fills almost completely the right atrium and rior vena cava and the subsequently reduced blood
prolapses through the tricuspid valve during right ven- flow through it. (d) CT scan showing the occlusion of the
tricular filling. (b ) Magnetic resonance imaging. Four- right jugular vein by the tumoral mass. LV left ventricle,
chamber view showing the size of the tumoral mass LJV left jugular vein, M mass, SVC superior vena cava,
(M) and its expansion within the right heart chambers. RA right atrium, RJV right jugular vein, RV right
(c ) Longitudinal view of the right atrium with supe- ventricle
Fig. 8.12 Secondary cardiac lymphoma. At transthoracic junction (dashed arrow). Thickened pericardium and dif-
echocardiography, the right ventricular free wall (arrow) fuse pericardial effusion are signs of pericardial involve-
appears thickened and hyperdense in both parasternal ment (courtesy of Pasquale Gianfagna, M.D.,
long-axis (a) and apical four-chamber (b) views. An addi- Cardiothoracic Department, Azienda Ospedaliero-
tional intramyocardial, hyperdense, and oval-shaped mass Universitaria, Udine, Italy). Ao aorta, LA left atrium, LV
can be appreciated at the posterior left atrio-ventricular left ventricle, RA right atrium, RV right ventricle
Secondary cardiac lymphomas show similar detection of intracardiac masses, the most com-
echocardiographic characteristics with primary mon cardiac manifestation of melanoma is sub-
cardiac lymphomas. Echocardiographic findings clinical because it frequently invades the
associated with cardiac metastases include the malig- pericardial surface [15]. Indeed, pericardial effu-
nant pericardial effusion, sometimes associated sion, with and without tamponade, is overall the
to tumor masses with bizarre surface structures. most common echocardiographic finding in met-
The infiltrated cardiac walls appear as having a astatic heart disease [24]. Solid material adherent
hyperdense pericardium and myocardium to the visceral or parietal pericardium (either
(Fig. 8.12). Wall motion abnormalities in these tumor or clotted blood) can be visualized within
regions are common. Application of echo con- the effusion.
trast agents can reveal the tumor perfusion and Both benign and malignant tumors can invade
helps the distinction of the metastasis from the the heart through the inferior vena cava. The most
surrounding tissue. common tumor that metastasizes to the heart
through the inferior vena cava is the renal cell
carcinoma (hypernephroma). Up to 43% of the
Metastatic Cardiac Tumors patients with hypernephroma demonstrate infe-
rior vena cava (Fig. 8.14) and/or right atrial
Cardiac metastases have been described in involvement [25]. Among benign tumors, intra-
autopsy series in up to 20% of patients with vascular leiomyomatosis of pelvic or uterine ori-
malignancies of other organs (Fig. 8.13) and are gin can reach the right heart through the inferior
up to 40 times more common than primary car- vena cava.
diac tumors [20, 23].
No malignant tumor preferentially metasta-
sizes to the heart; however, melanomas (up to Conclusions
64% of cases), leukemias, and lymphomas (up to
46%) are the tumors that most frequently mani- Cardiac masses frequently pose a diagnostic chal-
fest cardiac metastasis. Lung, breast, ovarian, and lenge. Due to its wide availability and cost-effec-
kidney cancer are also frequently involved [15, tiveness ratio, echocardiography is the first choice
20]. Although melanoma can manifest with the imaging modality for detection of cardiac tumors.
Fig. 8.13 Cardiac localization of metastases originating from can be easily differentiated from the surrounding myocardium
a malignant tonsil tumor. Transthoracic echocardiography (courtesy of Pasquale Gianfagna, M.D., Cardiothoracic
shows a hypodense, intramyocardial mass (M) localized at the Department, Azienda Ospedaliero-Universitaria, Udine, Italy).
apex of the right ventricle (a). In short-axis view (b), the mass LV left ventricle, RV right ventricle
Fig. 8.14 Renal cell carcinoma (hypernephroma). A chamber view (b) (courtesy of Pasquale Gianfagna, M.D.,
large hyperdense mass, filling almost completely the Cardiothoracic Department, Azienda Ospedaliero-
lumen of inferior vena cava and protruding into right Universitaria, Udine, Italy). IVC inferior vena cava, LA
atrium (arrow), can be appreciated at transthoracic left atrium, LV left ventricle, RA right atrium, RV right
echocardiography from both subcostal (a) and apical four- ventricle
Box 8.1 Practical Key Points for Echocardiographers
In the left or right atrium, the most common benign atrial masses are myxomas; clinical
context and contrast infusion provide important clues to distinguish from thrombi.
In the right atrium, the most frequent malignant tumors are angiosarcomas; other type of
sarcomas usually originate from the left atrium.
On cardiac valves, most common tumors are papillary fibroelastomas; clinical history and
hemocultures are key for differential diagnosis with vegetations.
In the ventricles and in children, rhabdomyomas and fibromas are the most frequent;
rhabdomyomas are usually multiple and decrease in size and number with age.
Malignant tumors are rapidly progressive and most commonly secondary; pericardium,
myocardium or veins with endocardial growth are typically involved, depending on their
way of spread.
Benign tumors may also be hemodynamically “malignant” by intramural growth, cavity
obstruction or systemic embolization; pericardial effusion, myocardial or valvular dys-
function may result from local invasion.
The various echocardiographic techniques (tran- the knowledge of typical imaging characteristics
sthoracic and transesophageal, contrast, and 3D and natural history of specific cardiac tumors is
ultrasound imaging) allow an accurate anatomic pivotal for an accurate non-invasive diagnosis.
localization and a precise description of these
masses, as well as an assessment of their hemody-
namic impact. For cases that are not so straight- References
forward, or for cases in which acoustic access is
restricted, magnetic resonance imaging and com- 1. Andrade MJ. Tumors and masses. In: Galiuto L,
Badano LP, Fox K, Sicari R, Zamorano JL, editors.
puted tomography scanning are preferred over
The EAE textbook of echocardiography. London:
echocardiography to assess contiguous extracar- Oxford University Press; 2011. p. 355–69.
diac involvement or the presence of metastatic 2. Auger D, Pressacco J, Marcotte F, Tremblay A, Dore
disease. Integration of available clinical data with A, Ducharme A. Cardiac masses: an integrative
approach using echocardiography and other imaging 13. Gowda RM, Khan IA, Nair CK, Mehta NU, Vasavada
modalities. Heart. 2011;97:1101–9. BC, Sacchi TJ. Cardiac papillary fibroelastoma: a
3. Meng Q, Lai H, Lima J, Tong W, Qian Y, Lai S. comprehensive analysis of 725 cases. Am Heart J.
Echocardiographic and pathologic characteristics of 2003;146:404–10.
primary cardiac tumors. Int J Cardiol. 2002;84: 14. Aziz F, Baciewicz FA. Lambl’s excrescences. Tex
69–75. Heart Inst. 2007;34:366–8.
4. Muller S, Feuchtner G, Bonatti J, Müller L, Laufer G, 15. Roberts WC. Primary and secondary neoplasms of the
Hiemetzberger R, Pachinger O, Barbieri V, Bartel T. heart. Am J Cardiol. 1997;80:671–82.
Value of transesophageal 3D echocardiography as an 16. De Cobelli F, Esposito A, Mellone R, Papa M,
adjunct to conventional 2D imaging in preoperative Varisco T, Besana R, del Maschio A. Late enhance-
evaluating of cardiac masses. Echocardiography. ment of a left ventricular cardiac fibroma assessed
2008;25:624–31. with gadolinium-enhanced cardiovascular mag-
5. Mehmood F, Nanda NC, Vengala S, Winokur TS, Dod netic resonance. Circulation. 2005;112:e242–3.
HS. Live three-dimensional transthoracic ecocardio- 17. Kirkpatrick JN, Wong T, Bednarz JE, Spencer KT,
graphic assessment of left atrial tumors. Sugeng L, Ward RP, DeCara JM, Weinert L, Krausz T,
Echocardiography. 2005;22:137–43. Lang RM. Differential diagnosis of cardiac masses
6. Asch FM, Bieganski SP, Panza JA, Weissman NJ. using contrast echocardiographic perfusion imaging.
Real-time 3-dimensional echocardiographic evalua- J Am Coll Cardiol. 2004;43:1412–9.
tion of intracardiac masses. Echocardiography. 18. Tollens M, Grab D, Lang D, Hess J, Oberhoffer R.
2006;23:218–24. Pericardial teratomas (prenatal diagnosis and course).
7. Plana JC. Three-dimensional echocadiography to Fetal Diagn Ther. 2003;18:432–6.
assess intra-cardiac masses. In: Badano LP, Lang RM, 19. Shanmugam G. Primary cardiac sarcoma. Eur
Zamorano JL, editors. Texbook of real-time three- J Cardiothor Surg. 2006;29:925–32.
dimensional echocardiography. London: Springer- 20. Burke A, Virmany R. Tumours of the heart and great
Verlag; 2011. p. 111–9. vessels. In: Burke A, Virmany R, editors. Atlas of
8. Mansencal N, Revault-d’Allones L, Pelage JP, Farcot tumour pathology. Washington, DC: Armed Forces
JC, Lacombe P, Dubourg O. Usefulness of contrast Institute of Pathology; 1996.
echocardiography for assessment of intracardiac 21. Ceresoli GL, Ferrei AJM, Bucci E, Ripa C, Ponzoni
masses. Arch Cardiovasc Dis. 2009;102:177–83. M, Villa E. Primary cardiac lymphoma in immuno-
9. Bednarz JE, Spencer KT, Weinert L, Sugeng L, Mor- competent patients: diagnostic and therapeutic man-
Avi V, Lang RM. Identification of cardiac masses and agement. Cancer. 1997;80:1497–506.
abnormal blood flow patterns with harmonic power 22. Zakja E, Badano LP, Sbrojavacca R, Malalan R,
Doppler contrast echocardiography. J Am Soc Gianfagna P, Fioretti PM. Unusual extension of an
Echocardiogr. 1997;12:871–5. intracardiac primary lymphoma to the right jugular
10. Lang-Lazdunski L, Oroudji M, Pansard Y, Vissuzaine vein. J Cardiovasc Med (Hagerstown). 2007;8:652–5.
C, Hvas U. Successful resection of giant intrapericar- 23. Peters PJ, Reinhardt S. The echocardiographic evalu-
dial lipoma. Ann Thorac Surg. 1994;58:238–40. ation of intracardiac masses: a review. J Am Soc
11. O’Connor S, Recavarren R, Nichols LC, Parwani A. Echocardiogr. 2011;19:230–40.
Lipomatous hypertrophy of the interatrial septum. 24. Goldman JH, Foster E. Transesophageal echocardio-
Arch Pathol Lab Med. 2006;130:397–9. graphic (TEE) evaluation of intracardiac and pericar-
12. Butany J, Nair V, Naseemuddin A, Nair GM, Catton dial masses. Cardiol Clin. 2000;18:860.
GM, Yau T. Cardiac tumours: diagnosis and manage- 25. Almasi GH. Surgery for tumors with cavoatrial exten-
ment. Lancet Oncol. 2005;6:219–28. sion. Semin Thorac Cardiovasc Surg. 2000;12:111–8.
New Cardiac Imaging Techniques:
Magnetic Resonance and Computed 9
Tomography
Massimo Lombardi
involvement, where MDCT reaches the highest

Introduction accuracy among the different techniques and can
be considered the reference method in the evalu-
Primary tumors of the heart and of the pericardium ation of lymph nodes. Furthermore, MDCT is
are rare with an incidence at autopsy ranging from extremely efficient in the detection of calcifications
0.0001 to 0.03%. Of these, the majority are benign within the tumoral mass. Among cons, the rela-
and about 50% are myxomas. Nowadays, the diag- tively low temporal resolution might lead to low-
nostic procedure implies an integrated use of cardiac quality images in the presence of tumoral masses
imaging tools such as echocardiography, either trans- with high mobility (Fig. 9.1). A MDCT study
thoracic or trans-oesophageal, and two techniques implies the administration of a large amount of
with a large field of view such as magnetic resonance ionizing radiations. When a benign tumor is
imaging (MRI) and multi-detector computerized suspected, with the possibility of even a complete
tomography (MDCT). The last two have significant healing (such as in the setting of a rhabdomyoma),
advantages and disadvantages which need to be con- the need of a regular and prolonged follow-up has
sidered for a better use of all the imaging modalities, to be considered in making the choice of the
with the purpose to obtain a final report as rich as better and less risky imaging technique, particu-
possible of details (stadiation, topographic relations, larly in a young patient.
hemodynamic effects, a probabilistic diagnosis of Another limit of MDCT remains the scarce
nature, etc.) to guide the following therapeutical capability to evaluate the involvement of cardiac
approach which implies the surgical option [1]. valves, although this can be easily overcome by
the integrated use of echocardiography.
At present, it seems reasonable to consider
Multi-detector Computerized among the advantages offered by MDCT its
Tomography capability to evaluate the coronary anatomy when
planning the surgical procedure, particularly in
Among the advantages offered by MDCT the people aged more than 40 years [2] (Fig. 9.2).
high spatial resolution is worthy of note mainly Published papers consist mostly of single
in the case of pulmonary, pleural, and mediastinal spectacular case reports [3, 4], but very few criti-
cal reviews do exist [5]. In general, MDCT can
be considered a very efficient diagnostic tool
M. Lombardi, M.D. (*) capable of answering critical questions raised
Cardiovascular MR Unit, Fondazione C.N.R./Regione
by the suspicion of a cardiac mass, besides the
Toscana “G. Monasterio”, S. Cataldo Research Campus,
Via Moruzzi. 1, 56010, Pisa, Italy presence of the mass itself, such as its anatomi-
e-mail: massimo.lombardi@ftgm.it cal relations with the surrounding structures, the
116 M. Lombardi
Fig. 9.1 Image obtained by MDCT scanner. Reprinted diastolic phase, the mass protrudes into the left ventricle
with permission of the Italian Society of Cardiology. A through the mitral valve orifice
mass is visible inside the left atrium (arrows). During the
Fig. 9.2 Image obtained by MDCT scanner. A huge mass (22 cm anterior–posterior diameter) is clearly evident.
The MDCT technique allows to identify the course of the branches of coronary arteries in relation with the mass
9 New Cardiac Imaging Techniques: Magnetic Resonance and Computed Tomography 117
Fig. 9.3 Image obtained by MDCT scanner. Reprinted of angiosarcoma. At the level of right lung, a small round
with permission of the Italian Society of Cardiology. At shaped lesion consistent with metastasis is also detectable
the level of the right atrium, a mass with irregular profile (courtesy of Dr. F. Cademartiri, Thorax Center, Rotterdam,
infiltrates both the pericardium and the myocardium The Netherlands)
(arrows). The findings are compatible with the diagnosis
infiltrative attitude (Fig. 9.3), the presence of of iodine contrast agent, the renal function has to
calcifications within the mass, and the presence be always assessed.
of hemorrhagic areas. To this purpose, the mea-
surement in Hounsfield Units (HU) in the differ-
ent regions of interest is mandatory. Unambiguous Magnetic Resonance Imaging
measurements can be performed only if high-
quality images are obtained by a ECG-gated The introduction of MRI for the evaluation of
MDCT scanner of last generation [4, 5]. Finally, cardiovascular diseases has considerably modified
if the operator has enough experience, MDCT, the diagnostic strategy of imaging in cardiac and
like MRI, allows to differentiate between tumoral paracardiac masses. Such technique provides a
and thrombotic masses [5]. complete multiplanar and noninvasive evaluation
The wide availability of MDCT scanners and a of the lesions involving the cardiac chambers,
diffuse experience of operators in the oncologic pericardium, and extracardiac structures, thus
field are important advantages for the use of this assuming a relevant role in providing diagnostic
technique when a cardiac mass is suspected. information useful for surgical planning. MRI is
Furthermore, a MDCT examination is relatively the most sophisticated imaging technique today
easy to perform, requires a reduced scanning time, available to characterize the tumoral mass in
and is usually well tolerated by the patient even in terms of morphology, dimensions, localization,
the case of a critical clinical picture. Although the extension, topographic relations, and infiltrative
limit of a high heart rate (which is often associ- aspects of the surrounding structures.
ated with an intracardiac mass) is nowadays less Furthermore, one of the most interesting prop-
relevant than in the past (high rotational speed, erties of MRI is the capability of differentiating
dual source technology, etc.), a heart rate more among the various tissues, due to the relative
than 80 beats per minute considerably reduces the differences in relaxivity which lead to high con-
quality of images. Finally, since MDCT examina- trast among the tissues. With obvious limitations,
tion implies the administration of a large amount a certain degree of tissue characterization is fea-
118 M. Lombardi
Fig. 9.4 Image obtained by MRI, SE T1 images. is visible. The mass appears hyperintense in SE T1 images
Reprinted with permission of the Italian Society of due to the adipose tissue
Cardiology. A lipoma (arrow) within the right atrial cavity
sible, such as the detection of lipomatous compo- kg) [6–8]. Often, a study of the dynamic of the
nents, necrotic areas, hemorrhage, calcifications, contrast medium impregnation is performed utiliz-
myxoid tissue, vascularity, etc. Nevertheless, a ing “ad hoc perfusion” T1-weighted sequences.
precise tissue characterization in terms of histo- Obviously, the greater the vascularity of the mass,
pathology is possible only in a few cases. the faster and more intense the contrast medium
Namely, it is almost definite when fat tissue is pre- impregnation would be. Dynamic sequences
dominant, such as in the setting of a lipoma, where (cine SPGR, SSFP, etc.) are also useful to assess
the capability of MRI to obtain images with fat the function of the involved cardiac structures,
suppression leads to a almost definitive diagnosis and the effect on adjacent tissues and on the
(Fig. 9.4). Similarly, myxoid tissue can be charac- intracardiac blood flow dynamic (Fig. 9.6).
terized very accurately (Fig. 9.5). However, in most These are generally quite lengthy studies
of cases the diagnosis of nature of the mass is which at times may bring the operator/physician
probabilistic, on the basis of certain findings very close to the nature of diagnosis.
which direct towards a kind of tumor rather than Properties of tissue composition affect the
another. signal characteristics of myocardium with cardiac
A correct characterization of the cardiac and MRI. The myocardium is a water-based tissue
paracardiac masses requires integrated informa- that contains a large number of hydrogen protons
tion that is obtainable with the different MRI and as such is ideally imaged with MRI. The sur-
sequences available. In other words, to properly rounding epicardial fat, the fibrous pericardium
characterize a cardiac or paracardiac mass, it is and masses that affect the heart show different MRI
necessary to obtain weighted images in either T1, signal characteristics, because they are composed
or T2, or IR (STIR), or T1/T2 , or T1 with spec- of tissues that contain varying amounts of water
tral fat suppression, or in GRE T2* (for possible or protons and therefore distort the signal charac-
calcifications or hemorrhages inside the mass), teristics of the normal myocardium. Thus, on the
and in T1 after contrast medium (0.1–0.2 mmol/ basis of tissue composition, MRI signal changes
Fig. 9.5 Image obtained by MRI, Triple-IR sequence been obtained by a Triple-IR sequence (STIR) and the
(STIR). Reprinted with permission of the Italian Society myxomatous tissue shows a marked hyperintense signal
of Cardiology. A large myxoma is detectable within the as compared to the surrounding structures. The signal
left atrial cavity. The mass is protruding into the left ven- hyperintensity in STIR images is always present in myx-
tricular cavity during the diastolic phase. The image has oid tissue, albeit this is not an exclusive characteristic
Fig. 9.6 Image obtained by MRI, SSFP sequence. ostium of a pulmonary vein. Right panel: during the car-
Reprinted with permission of the Italian Society of diac cycle (systolic phase), the myxomatous mass obsta-
Cardiology. Left atrial myxoma. Left panel: the tumoral cles the blood flow into the atrial cavity (temporal
mass is round shaped (arrow) and attached close to the resolution 35 ms)
120 M. Lombardi
Table 9.1 Characteristics of the MRI signal from differ- the mass, hemorrhagic areas (81% of cases),
ent tissues in the T1- and T2-weighted images thrombosis, or catabolites of hemoglobin
Contrast (e.g., hemosiderin), are often detectable [10]. If
Tissue T1 T2 agent the quantity of myxoid tissue is substantial, the lesion
Liquid Low(−−−) High (+++) Absent will have an elevated signal in the T2-weighted
Myxoid Low (−−−) High (+++) Scarce images (Fig. 9.5), while if the fibrous component
Collagen Low (−−) Low/high (−−/++)a Scarcea
prevails the mass will show a hypointense
Adipose High (+++) High (++) Absent
signal.
Necrosis Low (−−) High (+++) Absent
The presence of calcification is a common
Fibrous Low (−−) Low/high (−−/++)a Scarcea
Calcium Low (−−−) Low (−−−) Absent
finding (56%), particularly frequent in the myxo-
Vascularized Low (−−) High (++) Marked mas of the right atrium [11]. The calcium accounts
a
for the areas of low signal in the context of the
Signal and the contrast medium uptake depend on the
vascularization and cellularity of the tissues lesion, which is more evident in GRE T2* images.
The drop of signal may be caused also by the
effects of magnetic susceptibility, which are
and, in some instances, the nature of normal or related to the presence of iron [12]. On the other
abnormal tissue can be inferred. hand, the hemorrhagic areas might exhibit a high
Table 9.1 reports the characteristics of signal signal in both T1 and T2 sequences [13].
of the various tissue components useful for a It has been proven that the tumor enhancement
diagnostic orientation. after contrast medium administration depends on
its tissue composition and that the zones which
do not capture the contrast medium correspond to
Benign Atrial Tumors necrotic or cystic areas [14].
The differential diagnosis includes thrombotic
The benign lesions most frequently affecting the masses and other less common lesions, such as
atrial chambers are the myxoma and the lipoma. cardiac sarcoma and papillary fibroelastoma
The myxoma originates from the endocardium (Fig. 9.8).
as a polypoid, usually pedunculated mass (90%), MRI without contrast agent generally does
or at times sessile with a large base of implanta- not help in differentiating myxoma from intra-
tion; it shows mostly a smooth or, more rarely, a cavitary thrombus, because both can present
villous surface [9]. signal heterogeneity in SE images and low
The most typical location is the atrial chamber intensity in the GRE sequences [15]. However,
(left atrium 75%, right atrium 18%, right ventri- a myxoma shows very intense signal in IR T2 images
cle 4%, left ventricle 3%). and a significant enhancement after contrast
Usually, the left atrial myxoma is attached to agent administration, while the thrombotic for-
the interatrial septum at the level of the fossa ova- mation usually does not have such a behavior
lis; the stalk allows it to move freely inside the (Fig. 9.9) [16].
atrial chamber and sometimes to protrude into The papillary fibroelastoma is made up of
the left ventricle, during diastole, through the fibrous tissue, elastic fibers, and a single layer of
mitral valve orifice. endocardial cells. The tumor is usually small
Clinically, it can be asymptomatic or mimic a sized, round shaped, and attached to the endocar-
mitral stenosis. When the site of origin is not dium of the atrio-ventricular or semilunar valves
typical, differential diagnosis with other masses [17] (Fig. 9.8). In the literature, there are no sys-
is more difficult. tematic descriptions on the behavior of the MRI
Typically, the myxoma produces an inhomo- signal for such lesion, and the diagnosis is gener-
geneous signal due to the presence of fibrous, ally based on echocardiography, due to the rapid
necrotic, hemorrhagic, and sometimes calcified movements of the mass during cardiac cycle and
areas within the mass (Fig. 9.7). In the context of thus a not ideal visualization by MRI. However, it
Fig. 9.7 Image obtained by MRI, SE T1 after the admin- Gd-based contrast agent which is amplifying the disho-
istration of Gd. Reprinted with permission of the Italian mogeneity of signal intensity due to the composite struc-
Society of Cardiology. Left atrial myxoma (same case of ture of the tumoral mass (arrow) (myxoid, necrotic and
Fig. 9.5). Image in SE T1 after the administration of calcified areas)
is worth noting that T2 images’ signal intensity is suppression easily confirm the adipose nature of
usually lower in papillary fibroleastoma than in the mass.
myxoma.
The lipoma is a relatively rare cardiac tumor.
The properly called lipoma (Fig. 9.4) (encapsu-
lated or surrounded by myocardium) should be Benign Ventricular Tumors
clearly distinguished from the lipomatous hyper-
trophy of the interatrial septum. The latter entity Primary benign tumors of the ventricles are very
consists of a non-capsulated adipose tissue depo- rare in adults. The most frequent tumors of the left
sition, which extends onto the epicardial fat. Half ventricle are the fibroma and the rhabdomyoma,
of the cardiac lipomas are subendocardial; the which are more common in the pediatric
other half have a subepicardial and mesocardial population.
location [18]. The left atrium and left ventricle The rhabdomyoma is the most frequent tumor
are the most frequent locations. in children, and appears often as multiple nod-
Lipoma shows the characteristics of the MRI ules, either intramural or intracavitary. MRI sig-
signal typical of the adipose tissue, i.e., elevated nal characteristics are almost identical to those of
intensity of the signal in the T1- and T2-weighted the normal myocardium, as expected due to the
images. In this case, the techniques of fat origin of the tumor cells from cardiac myocytes.
122 M. Lombardi
Fig. 9.8 Image obtained by MRI. Reprinted with per- panel, image in SE T1: note the small, round shaped mass
mission of the Italian Society of Cardiology. Papillary (arrow). Right panel, image in SE T1: same mass after the
fibroelastoma of the sub-valvular mitral apparatus. Left administration of Gd-based contrast agent
Fig. 9.9 Image obtained by MRI, after contrast agent administration using an IR-GRE sequence. Reprinted with
permission of the Italian Society of Cardiology. Intraventricular apical thrombus (arrow)
The fibroma is the most frequent benign apex, or of the free wall. Hypointense signal
tumor of the left ventricle of the adult. It is usu- either in the T1 and in the T2 sequence is usu-
ally intramural and it appears as an area of ally detected. After administration of contrast
localized hypertrophy of the septum, of the medium, it appears as formed by a hypointense
Fig. 9.10 Image obtained by MRI. Reprinted with per- the peripheral border of the mass. Left panel: image in SE
mission of the Italian Society of Cardiology. Large fibroma T1. Central panel: image in SE T1 after the administra-
of the interventricular septum (arrows). The fibromatous tion of paramagnetic contrast agent. Right panel: image
mass does not show any change in signal intensity in the obtained by GRE-IR sequence after the administration of
different sequences utilized. After contrast agent adminis- paramagnetic contrast agent
tration, only a slight signal enhancement is detectable in
core surrounded by an isointense “shell” [19] the possible invasion of the pericardium, tumor
(Fig. 9.10). cells in the pericardial fluid are rarely found.
In the right ventricle, myxomas, fibromas, and Two variants of angiosarcoma are described,
rhabdomyomas can be found. i.e., a well-defined mass protruding into the atrial
cavity with preservation of the septum, or a dif-
fusely infiltrating mass extending along the peri-
Primary Malignant Cardiac Tumors cardium (Fig. 9.11). The presence of hemorrhage
and necrotic areas is frequent and accounts for the
The malignant tumors of the heart are less fre- typically heterogeneous signal of the tumor, which
quent (10%) than the benign ones and more usually presents high intensity areas in the
often localized in the right sections than in T1-weighted images, because of the presence of
the left. Autopsy studies report an incidence of meta-hemoglobin due to hemorrhagic phenomena.
0.001–0.28% [20]. Primary malignant tumors of In the setting of pericardial infiltration, a linear cap-
the heart are extremely rare [20] and constitute a ture along the vascular structures is detectable.
diagnostic dilemma as they are asymptomatic Undifferentiated sarcomas are malignant soft
until they reach significant dimensions, and, tissue tumors that are negative to multiple immu-
even in these cases, the symptoms and signs nohistochemical markers due to scarce or even
are usually nonspecific. The advent of sophisti- absent differentiation. The majority of cases are
cated imaging techniques has introduced the reported in the left atrium (Fig. 9.12). The prog-
possibility of detecting such lesions in patients nosis is generally poor. They usually appear as
still not compromised and sometimes as casual polypoid masses, isointense to the myocardium
findings, thus contributing to the characteriza- in MRI images, with wall thickening at the level
tion of the lesions and to the therapeutic of infiltration or with aspects similar to the
decision. angiosarcoma due to pericardial infiltration.
The angiosarcoma is the most frequent (37%) Rhabdomyosarcoma (4–7%) is a tumor which
among the primary malignant cardiac tumors [9]. originates from the muscular striated fiber. The
It originates from endothelial cells, most fre- embryonal variant is the more common form and
quently in the right atrium, with involvement of appears in infants, children, and young adults.
the pericardium, and frequently complicated by Despite the low incidence, such neoplasm repre-
pericardial hemorrhage and tamponade. Despite sents the most frequent form of malignant cardiac
124 M. Lombardi
Fig. 9.11 Image obtained by MRI. Reprinted with per- due to metahemoglobin (post hemorrhage). Right panel,
mission of the Italian Society of Cardiology. images after the administration of paramagnetic contrast
Angiosarcoma. Left panel, T1-weighted images (coronal agent: significant signal enhancement at the periphey of
plane): the tumoral mass shows an hyperenhanced area the mass
Fig. 9.12 Image obtained by MRI. Reprinted with permis- surrounded by necrotic and fibrotic areas (courtesy of Dr.
sion of the Italian Society of Cardiology. Undifferentiated Feola and Dr. Leonardi. Cardiologic Unit—Ospedale di
sarcoma of the left atrium (arrow). Histopathologic Cuneo, Italy)
findings showed a mixture of myxoid tissue and histiocytes
tumors in childhood. It can occur anywhere in the At difference from the metastatic osteosarcoma
myocardium and it involves the ventricular cham- that often occurs in the right atrium, the primary
ber more frequently than other types of sarcoma cardiac osteosarcoma most often involves the left
(Fig. 9.13). These tumors are often multicentric, atrium and is aggressive with a very poor progno-
usually intramural, and can involve the pericar- sis. The demonstration of bone component can be
dium. At difference from the angiosarcoma, the appreciated more easily through CT imaging.
myocardium is always involved and the pericar- Leiomyosarcoma usually originates from
dium often presents nodular masses. smooth muscle bundles of the subendocardial
The characteristics of the MRI signal are variable space, but they can also originate from the arteries
(isointensity to the myocardium, hyperintensity in T2 and pulmonary veins and spread to the cardiac
in correspondence of cystic-like or necrotic areas). structures. It has a predisposition for the left atrial
Osteosarcomas (nowadays called undifferenti- cavity, particularly at the level of the posterior wall.
ated pleomorphic sarcomas with areas of osseous Affected patients are typically in their fourth
differentiation) are a heterogeneous group of soft decade. Also in this case the MRI features are not
tissue sarcomas containing malignant cells that specific, i.e., lobulated masses, irregular in shape, often
produce bone and fibrotic or chondroid tissue. multiple with tendency to invade the pulmonary
Fig. 9.13 Image obtained by MRI, SE T1-weighted infiltration of cardiac walls, of the tricuspid valve and of
image. Reprinted with permission of the Italian Society the pericardium (arrows). The infiltrative growth and the
of Cardiology. Right atrial rhabdomyosarcoma. Large dimensions are in keeping with an aggressive malignant
mass involving right chambers of the heart, with diffuse tumor
veins or the mitral valve, showing an intermediate Primary cardiac lymphoma is a extra-nodal lym-
signal in T1 and a high one in T2. phoma that involves exclusively the heart and the
Fibrosarcoma is a rare primary malignant cardiac pericardium. Pericardial effusion is often present
tumor composed of fibroblasts and like other sarco- and drainage of the pericardial fluid, besides the
mas preferentially involves the left atrium. It can palliative effect, has a diagnostic purpose, since
also infiltrate the pericardial space, mimicking lymphoma cells are detectable in the majority of
mesothelioma. It can appear heterogeneous in MRI cases. Thoracotomic cardiac mass biopsy is also
images, but overall MRI features are not specific. frequently performed to achieve the diagnosis.
Liposarcoma is an extremely rare malignant Despite its rare occurrence, it is important to include
primary cardiac tumor that contains lipoblasts. primary cardiac lymphoma in the differential diag-
It has been usually described in the atria, although nosis of cardiac masses, since early chemotherapic
it has also been reported in the ventricles and in treatment can give excellent results [21].
the pericardium, where it can develop either with It mostly appears as multiple polypoid nod-
a nodular aspect or diffuse involvement. At dif- ules, infiltrating the myocardium with undefined
ference from the benign lipoma, the adipose borders and protruding into the cardiac chambers
component in primary liposarcoma is scarce or (Fig. 9.14). The site most frequently affected is
absent, thus explaining the limited value of MRI the right atrium; the pericardium is often involved
to achieve a precise histopathologic diagnosis. with thickening by tumor infiltration. As com-
pared with other primary malignant cardiac
126 M. Lombardi
Fig. 9.14 Image obtained by MRI. Cardiac lymphoma. Diffuse involvement of the pericardium and of the myocardium
of the right ventricle (arrow)
tumors, necrosis is less frequent. The MRI signal dimensions, structural homogeneity, infiltrative
is mostly hypointense in T1 and hyperintense in attitude of surroundings tissues, pericardial and
T2, but it has also been reported as isointense to pleural effusion, displacement of extracardiac
the myocardium; the enhancement pattern is also structures) and the uptake of contrast agent (see
quite variable (homogeneous, dishomogeneous). Table 9.2) were assessed in terms of diagnostic
accuracy. None of the considered characteristics
reached a sensitivity and a specificity of 100%.
Diagnostic Accuracy However, from the integrated use of all these
findings a diagnosis of high probability is
MDCT and MRI allow a sophisticated character- reachable.
ization of cardiac masses and not so rarely a diag- More recently, a multicenter experience of 78
nosis of the nature of the mass itself. The pediatric cardiac tumors evaluated by MRI dem-
differential diagnosis between benign and malig- onstrated that reviewers, who were blinded to the
nant masses is usually obtained. However, from histologic diagnoses, correctly diagnosed 97% of
the data available a more prudent approach seems the cases, but included a differential diagnosis in
indicated. In a review by Hoffman et al. [22] of 42% of cases [23]. Better image quality and more
more than 200 cardiac masses, the MRI signal complete examination were associated with higher
properties, the morphologic aspects (localization, diagnostic accuracy. However, histologic diagnosis
Table 9.2 Diagnostic accuracy of morphologic characteristics and uptake of Gd-based contrast agent
Characteristic Sensitivity Specificity PPV NPV
Localization 0.86 0.58 0.58 0.86
Signal dishomogeneity 0.86 0.48 0.53 0.84
Infiltrative attitude 0.64 0.70 0.58 0.74
Dimension >5 cm 0.55 0.78 0.67 0.68
Pericardial effusion 0.50 0.88 0.73 0.73
Pleural effusion 0.50 0.91 0.79 0.73
Pleural and pericardial effusions 0.59 0.82 0.68 0.75
Increase of signal after Gd c.a. 0.88 0.34 0.42 0.83
Modified from Hoffman et al. [22]
PPV positive predictive value, NPV negative predictive value, c.a. contrast agent
remained the gold standard and in some cases T1 images due to the paramagnetic effect of
malignancy could not be de fi nitively excluded metals bound to melanin [24].
on the basis of cardiac MRI alone. Among pericardial tumors, malignant primary
mesothelioma, that can manifest as an isolated
effusion or with pericardial thickening due to
Cardiac Metastases and Pericardial diffuse spreading or with bulky nodules, but without
Masses specific MRI signal characteristics (Fig. 9.17), is
worthy of note. Pleural mesothelioma can also
MRI is very useful in evaluating the extracardiac involve secondarily the pericardium.
extension of primary tumors of the heart, providing
the information needed to plan the most appropri-
ate surgical approach. Likewise, it allows to Conclusions
identify the presence of a cardiac involvement by
extracardiac masses with excellent anatomical Both MDCT and MRI have a very high value in
details. Therefore, when there is the suspicion of a the diagnostic workup of cardiac tumors. The
secondary involvement of the heart, the physician MDCT has reached a diagnostic accuracy which
generally asks for a MRI study. Moreover, metasta- was someway unexpected only a few years ago. It
ses to the heart and the pericardium are much more is the reference method to evaluate mediastinal
common than primary cardiac tumors. The malig- lymph nodes, and to assess lung and pleural
nant tumors that more often secondarily affect the involvement. Due to the relatively easy and stan-
heart and pericardium are breast and lung carcinomas dardized scanning procedure, MDCT can be pro-
(Figs. 9.15 and 9.16), melanoma, lymphoma, and posed as a robust method to detect cardiac and
leukemia. Cardiac metastases appear as pulmo- paracardiac masses, preferably in integration
nary or mediastinal masses that directly invade the with echocardiography. MRI remains the most
heart, or like masses that protrude into the left sophisticated tool in the clinical practice, although
atrium through the pulmonary veins or into the it is still available in a few specialized centers.
right atrium through the caval veins, or myocardial However, the experience accumulated in the
nodules. Sometimes, they can be suspected only recent years has shown that it can be considered
for the presence of pericardial effusion. The high as the reference cardiac imaging tool because it is
MRI contrast resolution allows to distinguish the capable of answering many of the questions
tumor from the myocardium and between tumor, raised by the presence of a cardiac mass.
thrombus, and flow artifacts much more easily Furthermore, the nonionizing nature of the tech-
than other techniques, sometimes helping also in nique induces to consider MRI as the ideal tool
tissue characterization. For instance, metastases for follow-up, at difference from MDCT. Finally,
from melanoma show a signal hyperintensity in the revision of the large amount of data available
128 M. Lombardi
Fig. 9.15 Image obtained by MRI, in fast GRE and sagittal oblique plane. Metastasis of breast cancer at the level of
right ventricular outflow tract (arrow)
Fig. 9.16 Image obtained by MRI. Metastasis of lung cancer involving the pericardium (arrows). Left panel: image in
SE T1. Right panel: image in triple-IR (STIR)
Fig. 9.17 Image obtained by MRI, SE T1-weighted Cardiology. Malignant mesothelioma of pericardium:
image after the administration of paramagnetic contrast note the presence of nodular thickening of the pericardium
agent. Reprinted with permission of the Italian Society of (arrows) with nonspecific signal characteristics
in scientific journals underline the need of an 6. Lombardi M, Bartolozzi C. Risonanza Magnetica del
cuore e dei vasi. Springer Verlag: Milano; 2004.
integrated use among the three imaging tech- 7. Higgins CB, De Roos A. Cardiovascular MRI and
niques (echocardiography, MDCT, and MRI) MRA. Philadelphia, PA: Lippincott Williams &
with the purpose to maximize the relative advan- Wilkins; 2003.
tages [25]. 8. Manning W, Pennell DJ. Cardiovascular magnetic reso-
nance. New York, NY: Churchill Livingstone; 2002.
9. Burke A, Virmani R. Tumors of the heart and great vessels.
Atlas of tumor pathology, 3rd series, fasc 16. Washington,
References DC: Armed Forces Institute of Pathology; 1996.
10. Grebenc ML, Rosado-de-Christenson ML, Green CE,
1. Butany J, Nair V, Naseemuddin A, Nair GM, Catton Burke AP, Galvin JR. Cardiac myxoma: imaging features
C, Yau T. Cardiac tumours: diagnosis and manage- in 83 patients. Radiographics. 2002;22:673–89.
ment. Lancet Oncol. 2005;6:219–28. 11. Burke AP, Virmani R. Cardiac myxoma: a clinico-
2. Mollet NR, Cademartiri F, van Mieghem CAG, Runza pathologic study. Am J Clin Pathol. 1993;100:671–80.
G, McFadden EP, Baks T, Serruys PW, Krestin GP, de 12. Seelos KC, Caputo GR, Carrol CL, Hricak H, Higgins
Feyer PJ. High-resolution spiral computer tomogra- CB. Cine gradient refocused echo (GRE) imaging of
phy coronary angiography in patients referred for intravascular masses: differentiation between tumor
diagnostic conventional coronary angiography. and nontumor thrombus. J Comput Assist Tomogr.
Circulation. 2005;112:2318–23. 1992;16:169–75.
3. Bootsveld A, Puetz J, Grube E. Incidental findings of 13. Masui T, Takahashi M, Miura K, Naito M, Tawarahara
papillary fibroelastoma on the aortic valve in 16 slice K. Cardiac myxoma: identification of intratumoral
multi-detector row computed tomography. Heart. hemorrhage and calcification on MR images. Am J
2004;90:e35. Roentgenol. 1995;164:850–2.
4. Wang HJ, Lin JL, Lin FY. Images in cardiovascular 14. Matsuoka H, Hamada M, Honda T, Kawakami H,
medicine. Cardiac hemangioma. Circulation. 2002; Abe M, Shigematsu Y, Sumimoto T, Hiwada K.
106:2520. Morphologic and histologic characterization of cardiac
5. Tatli S, Lipton MJ. CT for intracardiac thrombi and myxomas by magnetic resonance imaging. Angiology.
tumors. Int J Cardiovasc Imaging. 2005;21:115–31. 1996;47:693–8.
130 M. Lombardi
15. Gomes AS, Lois JF, Child JS, Brown K, Batra P. petent patients: diagnostic and therapeutic management.
Cardiac tumors and thrombus: evaluation with MR Cancer. 1997;80:1497–506.
imaging. Am J Roentgenol. 1987;149:895–9. 22. Hoffman U, Globits S, Schima W, Loewe C, Puig S,
16. Funari M, Fujuta N, Peck WW, Higgins CB. Oberhuber G, Frank H. Usefulness of magnetic
Cardiac tumors: assessment with Gd-DTPA resonance imaging of cardiac and paracardiac masses.
enhanced MR imaging. J Comput Assist Tomogr. Am J Cardiol. 2003;92:890–5.
1991;15:953–8. 23. Beroukhim RS, Prakash A, Buechel ER, Cava JR,
17. Edwards FH, Hale D, Cohen A, Thompson L, Pezzella Dorfman AL, Festa P, Hlavacek AM, Johnson TR,
AT, Virmani R. Primary cardiac valve tumors. Ann Keller MS, Krishnamurthy R, Misra N, Moniotte S,
Thorac Surg. 1991;52:1127–31. Parks WJ, Powell AJ, Soriano BD, Srichai MB, Yoo
18. Puvaneswary M, Edwards JRM, Bastian BC, Khatri SJ, Zhou J, Geva T. Characterization of cardiac tumors
SK. Pericardial lipoma: ultrasound, computed tomog- in children by cardiovascular magnetic resonance
raphy and magnetic resonance imaging findings. Aust imaging: a multicenter experience. J Am Coll Cardiol.
Radiol. 2000;44:321–4. 2011;58:1044–54.
19. Kiaffas MG, Powell AJ, Geva T. Magnetic resonance 24. Chiles C, Woodard P, Guiterriez R, Link KM. Metastatic
imaging evaluation of cardiac tumor characteristics in involvement of the heart and pericardium: CT and MR
infants and children. Am J Cardiol. 2002;89:1229–33. imaging. Radiographics. 2001;21:439–49.
20. McAllister Jr HA. Primary tumors of the heart and 25. Krombach GA, Spuentrup E, Buecker A, Mahnken
pericardium. Curr Probl Cardiol. 1979;4:1–51. AH, Katoh M, Temur Y, Higgins CB, Günther RW.
21. Ceresoli FL, Ferreri AJ, Bucci E, Ripa C, Ponzoni M, Heart tumors: magnetic resonance imaging and mul-
Villa L. Primary cardiac lymphoma in immunocom- tislice spiral CT. Rofo. 2005;177:1205–18.
Surgical Management
of Cardiac Neoplasms 10
Francesco Santini, Mariassunta Telesca,
Giuseppe Faggian, and Alessandro Mazzucco
Indeed in the last decades, major advances in

Introduction noninvasive cardiovascular diagnostic tech-
niques—especially echocardiography, computed
Primary cardiac tumors are rare forms of heart tomography, and magnetic resonance imaging
disease reported in both adult and children and (MRI)—have greatly facilitated the approach to
first described by Realdo Colombo in 1559 [1, 2]. cardiac neoplasm.
Several occasional reports are available on this Clinical signs and symptoms of a cardiac
topic in the past medical literature. In 1809, Burns tumor are often nonspecific and a high index of
described an atrial tumor determining valvular suspicion remains the most important element for
obstruction [3]. A series of six atrial tumors, prob- diagnosis. Indeed, cardiac neoplasms can pro-
ably myxoma, was published by King in 1845 [4]. duce a broad array of systemic findings, includ-
Barnes et al in 1934 made the first antemortem ing fever, cachexia, malaise, and arthralgias.
diagnosis of a cardiac sarcoma using electrocardi- Relevant signs and symptoms are considered:
ography and biopsy of a metastatic lymph node [5]. 1. progressive heart failure without apparent
In 1936, Beck successfully resected a teratoma cause, not responsive to medical therapy
external to the right ventricle [6], and Mauer 2. pericardial effusion, often hemorrhagic
removed a left ventricular lipoma in 1951 [7]. 3. persistent arrhythmias, Wolff-Parkinson-
However, prior to the advent of modern car- White syndrome, A–V blocks
diac surgery the correct antemortem diagnosis of 4. embolic phenomena and symptoms mimicking
an intracardiac tumor was largely academic, since systemic vasculitis or infective endocarditis
effective therapy was not possible. A new 5. severe dizziness or syncope
approach in the management of cardiac tumors 6. signs of valvular or sub-valvular obstruction
was made possible by the introduction of cardio- When suspecting a more conventional valvu-
pulmonary bypass by Gibbon in 1953, and by the lar and/or myocardial disease, the presence of
advent of echocardiography, which provided a atypical signs may raise the suspicion of cardiac
noninvasive method for accurately diagnosing tumors. For example, left atrial myxomas may
intracardiac mass [8–14]. produce auscultatory findings similar to mitral
stenosis, whose characteristics may change with
patient position, and mimic the symptoms of a
mitral disease. Furthermore, the well-described
F. Santini, M.D. (*) • M. Telesca, M.D • G. Faggian, M.D “tumor plop” is an early diagnostic sound
• A. Mazzucco, M.D
sometimes confused with a third heart sound.
Cardiac Surgery, University of Verona Medical School,
Piazzale Stefani 1, 37126, Verona, Italy The diagnostic tumor plop occurs just after the
e-mail: francesco.santini@univr.it opening snap of the mitral valve and is believed
132 F. Santini et al.
to be secondary to contact between the tumor and mation regarding the nature of the tumor by mea-
endocardial wall. suring X-ray attenuation, and possible tumor
Cardiac tumors may display several findings expansion to adjacent tissues. Multidetector com-
on plain chest roentgenograms, usually puted tomography (MDCT) is useful for the eval-
nonspecific. These include alterations in cardiac uation of calcification and fat content within a
contour, changes in overall cardiac size, specific mass. Furthermore, the high spatial resolution of
chamber enlargement, alterations in pulmonary MDCT is beneficial to define small lesions, mak-
vascularity, pericardial effusions, and intracar- ing this technique a useful tool for staging malig-
diac calcification (rhabdomyomas, fibromas, nant tumors. CT appears also useful in the
hamartomas, teratomas, myxomas, angiomas). evaluation of the potential involvement of peri-
Visualization of intracardiac calcium in an infant cardial and extracardiac structures. C-CT how-
or a child is unusual and should immediately ever provides less information regarding
raise the suspicion of an intracardiac tumor. characterization of tissues in comparison to car-
Mediastinal widening, due to hilar and paramedi- diac MRI. Disadvantages of the method also
astinal adenopathy, may indicate the spread of a include the use of radioactivity and of nephro-
malignant cardiac tumor. toxic contrast mediums [19–21].
Two-dimensional echocardiography, and more Cardiac magnetic resonance imaging (C-MRI)
recently real-time three-dimensional echocardiog- allows for a more sophisticated assessment of the
raphy [15], provide adequate information regard- tumor relation to adjacent structures, thus improv-
ing tumor size, attachment, and mobility, all ing the planning of a proper resection strategy. It
important variables to plan operative resection of also allows the detection of myocardial infiltration
the cardiac mass. It may also facilitate the differen- by the tumor and/or expansion of the mass to the
tiation between left atrial thrombus and myxoma. pericardium or to adjacent structures [19–21].
Moreover, continuous-mode Doppler ultrasonog- C-MRI may also contribute to the characteriza-
raphy may be useful for evaluating the hemody- tion of the composition of the tumor by studying
namic consequences of valvular obstruction and/ the signal in T1- and T2-weighted images, as
or incompetence caused by cardiac tumors. well as the enhancement of the signal after gado-
Transesophageal echocardiography provides linium administration [22]. Recent technologic
an unimpeded view of the cardiac chambers and advances in cardiac MRI have resulted in the
atrioventricular (AV) septa and appears to be supe- rapid acquisition of images of the heart with high
rior to transthoracic echocardiography in many spatial and temporal resolution and excellent
patients. Its potential advantages include improved myocardial tissue characterization [23].
resolution of the tumor and its attachment, and the Furthermore, administration of contrast medium
ability to detect small masses not visualized by may help to differentiate a cardiac tumor from a
transthoracic echocardiography (<3 mm diameter). thrombus and/or from blood flow artifacts
Transesophageal echocardiography has been rou- [19–23].
tinely used to guide the percutaneous biopsy of Cardiac catheterization and selective angio-
right-sided cardiac masses, thus allowing success- cardiography are usually not necessary since
ful sampling of the target tissue for preliminary adequate preoperative information may be
histologic evaluation [16]. Transesophageal obtained by one or more of the above-mentioned
echocardiography should always be considered less invasive imaging techniques. However, sev-
when the transthoracic study is suboptimal or con- eral circumstances exist in which the risk and
fusing [17, 18]. expense of cardiac catheterization are outweighed
Cardiac computed tomography (C-CT) can by the supplemental information it may provide.
provide useful information in view of its high These situations include cases in which (a)
resolution and ability to accurately depict cardiac noninvasive evaluation has not been adequate; (b)
morphology without limitations because of a malignant cardiac tumor is considered likely
acoustic windows. It can also provide some infor- (cardiac angiography may provide valuable
10 Surgical Management of Cardiac Neoplasms 133
information regarding the degree of myocardial, myxomas started to be removed successfully on a

vascular, and/or pericardial invasion, as well as more routine-based approach [8, 32].
visualization of the vascular supply of the tumor, Currently, operative excision is the treatment
the source of its blood supply, and its relation to of choice for most benign cardiac tumors, very
the coronary arteries); and (c) other cardiac often resulting in a complete cure. Although
lesions may coexist with a cardiac tumor (i.e., many cardiac tumors appear histologically
coronary artery disease) and possibly dictate a benign, they all are potentially lethal as a result of
different surgical approach [24, 25]. intracavitary or valvular obstruction, peripheral
The major angiographic findings in patients embolization, and/or disturbances of rhythm or
with cardiac tumors include (a) compression or conduction. Therefore, it is mandatory to carry
displacement of cardiac chambers or large ves- out the operation promptly after the diagnosis is
sels, (b) deformity of cardiac chambers, (c) intra- established [13, 14, 33–35].
cavitary filling defects, (d) marked variations in Through a median sternotomy, intramural and
myocardial thickness, (e) pericardial effusion, intracavitary tumors must be excised under direct
and (f) local alterations in wall motion [24, 26]. vision using the heart–lung machine (Fig. 10.1)
The major risk of angiography is peripheral with bicaval or femoral cannulation (Fig. 10.2).
embolization due to dislodgement of a fragment The potential dislodgment of tumor fragments
of tumor or of an associated thrombus. constitutes one of the major risk of the operation
The diagnosis of cardiac tumors and the esti- and may result in peripheral emboli and/or the
mation of their grade cannot be made with the dispersion of micrometastases, which may seed
sole use of imaging methods and histological peripherally. To reduce this risk, manipulation of
confirmation is always necessary. This can be the heart prior to cardiopulmonary bypass and
achieved with minimally invasive techniques, aortic cross-clamp positioning should be mini-
such as cytological examination of pericardial or mized (“no-touch technique”), as in other cir-
pleural fluid, or by means of echocardiographi- cumstances when dealing with any intracardiac
cally aided percutaneous or transvenous cardiac friable mass (i.e., thrombus).
biopsy. In cases where diagnosis cannot be estab- During the preliminary maneuvers to set the
lished, biopsy via thoracoscopy or even thoraco- cardiopulmonary bypass, a transesophageal
tomy may be needed [16, 27, 28]. echocardiography may result extremely useful to
define in detail the anatomy of the intracardiac
mass, its relationship with any valvular apparatus,
Primary Benign Cardiac Tumors to guide in an uneventful cannulation of the car-
diac chambers, and to monitor the integrity of the
Surgical Technique tumor during the initial surgical manipulations.
The surgical management of cardiac tumors After establishing cardiopulmonary bypass,
began in 1936 when Beck successfully resected a under mild hypothermia, the heart is separated
teratoma external to the right ventricle [6]. In from the systemic circulation by an aortic cross-
1951 Mauer resected a left ventricular lipoma [7] clamp followed by the infusion of blood or crystal-
and Bhanson and Newman in 1952 removed a loid cardioplegia administered antegradely into
large right atrial myxoma using inflow caval the aortic root, and/or retrogradely into the coro-
occlusion [29]. In 1954 Crafoord for the first time nary sinus. Although some epicardial tumors may
removed successfully a left atrial myxoma using be removed without the aid of extracorporeal cir-
cardiopulmonary bypass [30], whereas Kay et al. culation, intramural and intracavitary tumors must
first removed a left ventricular myxoma in 1959 be excised under direct vision. The surgical
[31]. By the early sixties, owing to the progres- approach will depend on the location of the cardiac
sive safety of cardiopulmonary bypass and to the mass (right-, left-, combined atriotomy, aortotomy,
increased use of echocardiography, atrial etc.). In view of the potential multifocal location of
Fig. 10.1 Diagram of a cardiopulmonary bypass circuit. blood exits the oxygenator and passes through a filter/
Venous blood is drained from the venae cavae/right atrium bubble trap to the aortic cannula, which is usually placed
into the venous reservoir which is incorporated in the in the ascending aorta. Suction systems and sources of
membrane oxygenator/heat exchanger unit. Arterialized gases are also represented
the cardiac tumors, all the cardiac chambers will Every care should be taken to remove the
need to be systematically explored. A good surgi- tumor without fragmentation. After tumor resec-
cal exposure represents the fundamental principle tion, the surgical field should be irrigated and
to accomplish a complete, possibly en bloc, resec- carefully inspected for loose fragments. Whether
tion of the tumor. The ideal resection aims to blood removed from the surgical field during
include the tumor and a portion of the cardiac wall tumor manipulation should be discarded or
and/or interatrial septum, to which it is attached, returned to the pump circuit is controversial.
spared by the disease. Variables with an impact on Usually the cardiotomy suction is used during the
tumor resection are location, involvement of the operation, but the sole wall suction is utilized
myocardium and/or fibrous skeleton of the heart, during the brief time that the tumor is actually
and histology. To overcome the technical chal- excised in order to avoid tumor macroemboli
lenges of complete resection with accurate cardiac entering the bloodstream via the perfusion circuit
reconstruction, particularly of left-sided tumors and the cardiotomy reservoir [8, 39, 40].
with posterior extension, a technique of cardiac In the event of friable tumors located in the
explantation, ex vivo tumor resection with cardiac left (or right) cardiac chambers, the aorta (or the
reconstruction, and cardiac reimplantation—car- pulmonary artery) should be independently
diac autotransplantation—has been successfully explored to exclude intraoperative migration of
utilized [36–38]. loose tumor fragments beyond the semilunar
Fig. 10.2 Cannulation of Superior

the superior and inferior Vena Cava
vena cava from incision in
the right atrium. Caval
snares are always used to
allow safe opening of the
right atrium Aorta
Pulmonary
Artery
Right
Atrium
Right
Ventricle
Inferior
Vena Cava
valves. The use of an intra-aortic filter (Edwards this is not possible, a valve prosthesis may be
Embol-X System, Edwards Lifescience, Irvine used.
CA) may help to reduce the event of systemic The major surgical consideration in excision
embolization in case of friable tumors located in of ventricular tumors includes location, poten-
the left cardiac chambers [41]. tial for a complete resection, preservation of
Ventricular tumors are usually approached adequate ventricular myocardium, maintenance
through the AV valves if located in the ven- of proper AV valve function, and preservation of
tricular in fl ow, or through the semilunar the conduction system. It is not always possible
valves when located in the ventricular out fl ow to remove a ventricular tumor completely, and
tract. partial removal is only palliative. Children with
In the event of tumors involving a cardiac extensive fibromas have been treated with car-
valve, the surgical strategy should still aim to a diac transplantation. In selected cases of right
complete resection of the mass, although trying ventricular tumors, a right heart bypass (cavo-
to preserve the native valve by means of several pulmonary anastomosis) has also been utilized
well-described reparative techniques. When [11–14, 33, 42–48].
Fig. 10.3 (a) Diagram of a left atrial myxoma (75% of (myxoma) (asterisk) attached to the interatrial septum. RA
all cases) attached to the interatrial septum, above the right atrium, RV right ventricle, LV left ventricle
mitral valve. (b) Cardiac-CT showing a left atrial mass
Coming off cardiopulmonary bypass, through the anterior wall of the left atrium, ante-
transesophageal echocardiography may provide rior to the right pulmonary veins, eventually
useful information on complete tumor excision, extended behind both cavae to achieve greater
valve/prosthesis function in case of repair/ exposure. Exposure and removal of large tumors
replacement, absence of residual shunt in case of attached to the interatrial septum however may
septal reconstruction, myocardial function, and be facilitated by a right atrial approach, which
de-airing. allows easy removal of tumor attached to the
fossa ovalis with full-thickness and large exci-
Left Atrial Myxoma sion at the site of attachment and easy patch clo-
Myxoma is the most common type of primary sure of the atrial septum if necessary (Fig. 10.4a,
cardiac tumor, accounting for 1/3 to 1/2 of all b) [49]. As mentioned, the tumor should be
cases. They may occur in any chamber of the removed without fragmentation. Nevertheless,
heart but have a special predilection for the left after removal the surgical field should be irri-
atrium, from which approximately 75% origi- gated and inspected for loose fragments. In case
nate. Left atrial myxomas generally arise from of atrial wall rather than septal attachment, large
the interatrial septum at the border of the fossa full-thickness excision of tumor insertion should
ovalis (Fig. 10.3a, b), but can originate any- be aimed whenever possible. A systematic
where within the atrium, including the append- inspection of the other cardiac chambers to
age. Surgical resection is the only effective exclude other tumor location potentially over-
therapeutic option for patients with cardiac looked by the utilized imaging techniques is
myxoma and should not be delayed because always recommended.
death from obstruction to flow within the heart Histologic evaluation of the primary lesion is
and/or embolization may occur in as many as obviously mandatory to elaborate the most appro-
8% of patients awaiting operation [8]. Left atrial priate patient management and follow-up [11–14,
myxomas can be approached by an incision 33, 35, 42, 49–51].
Fig. 10.4 (a) Right atriotomy and exposure of the left tricuspid valve. (b) Left atrial myxoma with its base of
atrial myxoma through the fossa ovalis. Reprinted with attachment to the interatrial septum, excised with
permission of the Italian Society of Cardiology. TV surrounding tissue
Right Atrial Myxoma using pericardium or polytetrafluoroethylene,

About 10 to 20% of all cardiac myxomas are keeping in mind that resection of large or criti-
found in the right atrium. Right atrial myxomas cally placed right atrial myxomas may require
are more likely to have broad-based attachments; careful preoperative planning and special perfu-
they also are more likely to be calcified and thus sion strategies. The tricuspid valve and the right
visible on chest radiographs. Right atrial myxo- atrium, as well as the left atrium and ventricle,
mas can produce signs and symptoms of right- should always be inspected carefully for multi-
sided heart failure with venous hypertension, centric tumors in patients with right atrial myx-
hepatomegaly, ascites, and dependent edema. oma, with or without familial occurrence
The tumor may also simulate tricuspid valve [49–51].
stenosis by partially obstructing the valve orifice.
If a patent foramen ovale is present, right-to-left Ventricular Myxomas
atrial shunting may occur with central cyanosis, Ventricular myxomas (6–8%) occur more often
and possible paradoxical embolization [8]. in women and children and may be multicentric
When approaching right atrial myxomas, intra- [12–15, 53]. Right ventricular tumors typically
operative echocardiography may be extremely arise from the free wall, and left ventricular
helpful to promote safe venous cannulation, tumors tend to originate in the vicinity of the pos-
avoiding mass trauma and/or poor venous return terior papillary muscle.
related to an impinging tumor. Both venae cavae Ventricular myxomas may be approached
may be cannulated directly and caval snares are directly through the AV valve or by detaching
always used to allow opening of the right atrium. portion of the AV valve, for mass exposure and
However, when low- or high-lying tumor pedicles resection, and reattachment after excision. Small
preclude safe transatrial cannulation, cannulation tumors in either outflow tract can be removed
of the jugular or femoral vein can provide venous through the outflow valve [8]. If necessary, the
drainage of the upper or lower body [52]. The tumor is excised through a direct incision into the
right atrium may be opened widely for resection ventricle, but this is unusual. It is not necessary to
of the tumor and reconstruction of the atrium remove the full thickness of the ventricular wall
because no recurrences have been reported with Lipoma

partial-thickness excisions [49–51]. As men- Lipomas are well encapsulated primary benign
tioned for right atrial myxoma, in the presence of cardiac tumors, and consist of mature fat cells
a ventricular myxoma inspection for other tumors [9–12]. They are usually located in the subepicar-
is highly recommended because of the high inci- dium, in the left ventricle, in the right atrium, and
dence of multiple locations. in the interatrial septum (Fig. 10.5a, b). The non-
Overall 30-day mortality after removal of an encapsulated hypertrophy of the fat within the
atrial myxoma is below 5%, although excision of atrial septum, often in continuity with the epicar-
ventricular myxomas carries a higher risk dial fat, is known as lipomatous hypertrophy.
(approximately 10%). Operative mortality may Lipomatous hypertrophy is more common than
be increased by tumor unrelated variables such as cardiac lipoma, is more frequent in elderly, obese
advanced age, disability, and/or comorbidities. patients, and is usually an incidental finding dur-
Long-term survival, freedom from complication, ing a variety of cardiac imaging or surgical
and quality of life are excellent in the nonfamilial procedures.
form of myxoma [35, 48–51, 54, 55]. Often asymptomatic and incidentally discov-
The recurrence of an intracardiac myxoma ered on routine chest roentgenogram, echocar-
(described by 6 months and up to 11 years after diogram, or at surgery, lipomas may cause
the resection) may be related to an inadequate arrhythmias, conduction system disturbances,
original resection, when at the same site of the symptoms of heart failure, and sudden death,
original tumor, or to the presence of neoplastic especially in cases where they reach a large size
fragments. Recurrence of nonfamilial sporadic [58–60]. Large lipomas, particularly when asso-
myxoma is approximately 1–4% and possibly ciated with severe symptoms, should be resected.
lower in patients with a normal DNA genotype Smaller, asymptomatic tumors, incidentally dis-
[55, 56]. The rarer subgroup of patients with spo- covered during cardiac operation undertaken for
radic myxoma and abnormal DNA have a recur- different indications, should be removed if exci-
rence rate estimated at between 12 and 40%. sion is doable without adding risk to the primary
The recurrence rate is highest in patients with procedure. In case of location in the atrial sep-
familial complex myxomas, all of whom exhibit tum, patch reconstruction may be necessary.
DNA mutation [56]. Overall, recurrences are Cardiac lipomas are not known to recur.
more common in younger patients. Most recur-
rent myxomas occur in the same or different car- Papillary Fibroelastoma
diac chambers, and may be multiple particularly Papillary fibroelastomas are the most common
in familial complex myxomas. Extracardiac tumors of the cardiac valves, accounting for 75%
recurrence after myxoma excision, likely from of all valvular tumors (Fig. 10.6a). They usually
embolization, local tumor growth, and invasion, affect the elderly (age range 60 ± 16) [61], are
has been observed in the brain, arteries, soft tis- generally small in size (<1 cm), and affect mainly
sue, and bones [8]. the aortic or the mitral valve, even though tricus-
In view of these considerations, patients who pid and pulmonary valves may also be affected.
are treated initially for multicentric tumors, those Occasionally, papillary fibroelastomas locate in
whose tumors are removed from unusual loca- the left ventricle, more often in the outflow tract,
tions in the heart or believed to have been incom- can be multifocal, and are associated with the
pletely resected and/or those with an abnormal hypertrophic obstructive cardiomyopathy [62–64].
DNA genotype, should be closely followed up Papillary fibroelastomas resemble a sea anemone
[56, 57]. Furthermore, in those cases with delayed with frond-like projections comprising dense
evidence of malignant characteristics within a elastin at the core of each frond, coated with col-
resected mass mistakenly thought to be an inno- lagen and lined by flat endocardial cells.
cent myxoma, complete patient rescreening is Although frequently asymptomatic and often
mandatory. incidental findings at autopsy, papillary
Fig. 10.5 (a) Cardiac-MRI of a huge lipomatous hyper- excised lipoma. Hematoxylin and eosin staining shows
trophy located in the interatrial septum (asterisk). RV right mature adipocytes (×100)
ventricle, LV left ventricle. (b) Microscopic views of the
fibroelastomas are capable of producing obstruc- specimen suggests the possibility of a virus-
tion of flow, particularly coronary ostial flow induced tumor, therefore evoking the concept of a
when located on the aortic valve (Fig. 10.6b). chronic form of viral endocarditis [66].
Most importantly, they may embolize to the coro-
nary system or to the brain (or to the lung when Fibroma
right-sided), with potential life-threatening com- Fibromas are the second most common cardiac
plications. Therefore, papillary fibroelastomas tumor of childhood, although they may also affect
should be resected whenever diagnosed. In the the adult population. These are solitary non-
event of a potential underlying coronary artery infiltrating intramural tumors, usually located in
disease, invasive coronary angiography poses a the left ventricle, mainly in the interventricular
significant risk of stroke in case of localization of septum, and they are often mistaken for hypertro-
the mass at the aortic valve level. In these patients, phic cardiomyopathy or apical thrombus
multislice-CT coronary angiography should be (Fig. 10.8). Fibromas are non-encapsulated, firm,
considered as a safer alternative [65]. Standard nodular, gray–white tumors potentially bulky,
cardiopulmonary bypass with bicaval cannulation composed mainly of interlacing bundles of dense
and conventional myocardial protection is utilized collagen and elastic fibers, and elongated
for tumor resection. Valve repair rather than fibroblasts. Deposits of calcium may be present.
replacement should follow the resection of these Symptoms may be related to chamber obstruc-
benign tumors whenever technically feasible, tion, impairment of contraction, and/or arrhyth-
using conservative margins of resection with no mias. Depending on size and location, fibromas
observed recurrence after complete excision may interfere with valve function, obstruct flow
(Fig. 10.7a, b). In the rarer cases of a multifocal paths, or cause sudden death from conduction
valve localization, valve replacement may be disturbances [8]. Surgical approach requires stan-
required. Worthy of note, the reported presence of dard cardiopulmonary bypass with bicaval can-
dendritic cells and cytomegalovirus in the resected nulation and conventional myocardial protection.
Fig. 10.6 (a) Transesophageal echocardiogram of a LA left atrium, LV left ventricle, Ao aorta. (b) Intraoperative
papillary fibroelastoma attached to the aortic valve (arrow). view showing the papillary fibroelastoma attached to the
Reprinted with permission of the Italian Society of Cardiology. right coronary aortic valve cusp (asterisk/arrow)
Fig. 10.7 (a) Papillary fibroelastoma after resection, with the typical sea anemone shape. (b) Diagram of an aortic
valve patch reconstruction after repair. Reprinted with permission of the Italian Society of Cardiology.
Fig. 10.8 Cardiac-MRI of

a fibroma involving the
right atrium and ventricle
(asterisk), with associated
pericardial effusion
(arrow). Reprinted with
permission of the Italian
Society of Cardiology. RA
right atrium, RV right
ventricle, LA left atrium,
LV left ventricle
Complete resection is usually successful when 72], it usually presents during the first few days
the tumor is localized, does not involve coronary after birth. Occasionally sporadic, it is quite often
arteries, AV valves, and/or the fibrous skeleton of associated with tuberous sclerosis (hereditary
the heart, and can be enucleated, usually through disorder characterized by hamartomas, seizures,
an epicardial approach, without entering the ven- developmental delay and behavioral problems,
tricle whenever possible. Video-assisted cardios- sebaceous adenomas) [53, 73, 74].
copy has been recently reported as a suitable and Rhabdomyomas are variable in size, usually
useful technique to assist removal of primary left multiple, and they affect the right and the left
ventricular fibroma with intracavitary extension ventricle likewise. Firm, gray, nodular, and often
[67]. Complete excision is usually curative. On intramural, they tend to project into the ventricu-
the other hand, partial tumor removal is palliative lar cavity, thus causing mechanical complica-
although often followed by a prolonged survival tions, such as obstruction of the ventricular
[68]. Children with extensive fibromas, in good outflow tract. On histology, they show large myo-
overall clinical conditions and with no specific cytes filled with glycogen and containing hyper-
contraindications, have been successfully treated chromatic nuclei. As for other intracardiac
with orthotopic cardiac transplantation [69]. In masses, clinical signs and symptoms depend on
selected cases of extensive right ventricular the size, location, and number of the tumors.
tumors, a right heart bypass (cavo-pulmonary Frequently enough, rhabdomyomas cause heart
anastomosis) (Fig. 10.9a, b, c) has also been uti- failure obstructing cardiac chambers and/or valvu-
lized [11–14, 33, 42–48] as a palliative solution lar orifice flow. Onset of symptoms may be repre-
or as a bridge to orthotopic cardiac transplanta- sented by arrhythmias, particularly ventricular
tion [70]. tachycardia, although sudden death may be the
only effect of an undisclosed cardiac rhabdomy-
Rhabdomyoma oma. Surgery may be advisable in symptomatic
Rhabdomyoma represents the most common car- patients, without tuberous sclerosis, before 1 year
diac tumor in children. Thought to be a myocar- of age. The tumor is removed easily in early
dial hamartoma rather than a true neoplasm [71, infancy, and despite being non-encapsulated
Fig. 10.9 Right heart bypass [cavo-pulmonary anasto- the Italian Society of Cardiology. MRI control (c). RA
mosis (b, diagram)] in a case of extensive non-resectable right atrium, RV right ventricle, LA left atrium, LV left
right ventricular tumor (a, asterisk; arrows indicate resid- ventricle, p-SVC proximal superior vena cava, d-SVC dis-
ual right ventricular cavity). Reprinted with permission of tal superior vena cava, RPA right pulmonary artery
some can be completely resected. Partial resec- Primary malignant tumors are relatively rare,
tion may be conceivable to release the obstruc- accounting for upto 25% of all primary cardiac
tion [75]. However, whenever planning a surgical tumors in third level referral centers. They usu-
strategy, it has to be considered that rhabdomyo- ally affect people aged 30–50 years, and are
mas may regress spontaneously after birth, thus mainly represented by sarcomas (angiosarcoma,
limiting indication to surgical resection to the rhabdomyosarcoma, leiomyosarcoma, liposar-
actual symptomatic cases [73]. coma, osteosarcoma, fibrosarcoma, and malig-
In case of multiple and extensive tumors, par- nant fibrous histiocytoma) and lymphomas
ticularly in patients with tuberous sclerosis, sur- [9–14]. Angiosarcomas are usually located in the
gery offers little benefit. right chambers of the heart (Fig. 10.10a, b),
Other benign cardiac tumors (hemangioma, whereas other sarcomas affect the left atrium
teratoma, paraganglioma, pheochromocytoma, more frequently. Lymphomas with bi-atrial local-
cystic tumors of the AV node, etc.) are rarely ization have also been reported (Fig. 10.11) [76].
observed. As mentioned, clinical signs and Malignant tumors have usually a poor prognosis
symptoms will be a result of intracavitary and/or in view of the extensive infiltration of the myo-
valvular obstruction, peripheral embolization, cardium, the frequent obstruction of intracardiac
and disturbances of rhythm or conduction, flow, and the occurrence of metastases [28].
including sudden death. After the diagnosis, Indeed, a metastatic spread has been demon-
strict patient surveillance and multidisciplinary strated at autopsy in more than 75% of all
decision making relative to surgical indication patients who died of a primary cardiac sarcoma,
are mandatory. mostly involving lungs, mediastinal lymph
nodes, and spine. The nonspecific clinical signs
and symptoms include congestive heart failure,
Primary Malignant Tumors dyspnea, atypical chest pain, malaise, anorexia,
and weight loss. Arrhythmias, syncope, sudden
Malignant cardiac tumors continue to pose a death, pericardial effusion, and tamponade have
therapeutic challenge to cardiac surgeons and also been reported [77]. Chest X-ray can offer
oncologists because of the technical difficulty indirect findings from the enlargement of car-
involved in extensive cardiac resections and the diac chambers, the occurrence of calcification,
aggressive biological nature of the tumors. or pericardial effusion. Two-dimensional echocar-
Fig. 10.10 (a) Cardiac-MRI of an angiosarcoma involv- tricle. (b) Intraoperative view of the tumor (asterisk), with
ing the right atrium and the right atrio-ventricular junction multilobulated extensions (arrows)
(asterisk). RA right atrium, RV right ventricle, LV left ven-
Fig. 10.11 Modified

four-chamber echocardio-
graphic view. Bi-atrial
lymphoma filling almost
entirely the right atrium
(asterisk) and less
extensively the left atrial
chamber (double asterisk).
RA right atrium, LA left
atrium
diography provides adequate information regarding assessing its resectability. Cardiac catheterization
tumor location, size, attachment, and mobility all may offer useful information about myocardial,
important variables to plan operative resection of vascular, and/or pericardial infiltration, and on
the cardiac mass. If malignancy is suspected, the presence of tumor feeding vessels. Malignancy
chest CT and/or MRI may grossly guide on the may be suggested and coronary involvement sus-
histologic nature of the mass and provide detailed pected by the evidence of a tumor blush
anatomy of the tumor, thus helping in staging and (Fig. 10.12a, b), although this finding is not
Fig. 10.12 Typical tumor blush (arrows) at coronary angiography in right atrial sarcomas
pathognomonic having been found also in myxo- right heart sarcomas, left heart sarcomas, and
mas [8]. Finally, transesophageal echocardiog- pulmonary artery sarcomas.
raphy guided transvenous endomyocardial If complete resection is possible, respecting the
biopsy is a very important tool to define tumor anatomical and functional integrity of the heart,
histology and to interpret metastatic lesions, surgery provides better palliation and can improve
thus helping to plan the most efficacious thera- survival vs. medical therapy alone [76–82].
peutic strategy which usually involves a combi- As previously mentioned, a good surgical expo-
nation of surgery, chemotherapy, and radiation sure represents the fundamental principle to accom-
therapy [77–80]. plish a complete, possibly en bloc, resection of the
The decision to resect a primary malignant tumor, encompassing the mass and about 1 cm por-
tumor is based on several variables, including tion of the surrounding cardiac tissue. Besides the
tumor location and size, histology, grade of myo- routine use of cardiopulmonary bypass, deep hypo-
cardial infiltration, relationship with the cardiac thermia with circulatory arrest (<18 °C rectal tem-
valves and the fibrous skeleton of the heart, perature), providing a bloodless field unencumbered
absence of metastatic spread, and potential for a by cardiopulmonary bypass cannulas, can greatly
radical excision of the mass. Other more general improve exposure. Surgery may be technically
variables, such as age, overall clinical conditions, demanding and the necessity of securing negative
frailty, and comorbidities, will also need to be margins may entail further interventions such as
considered to finalize the surgical strategy [34, coronary artery bypass, valve replacement, recon-
36, 76–82]. structive procedures, pacemaker implantation, and
Currently, chemotherapy, radiation therapy, or pericardial repairs, thus resulting in an increased
a combination of both are used as an adjuvant to risk of postoperative complications.
decrease tumor size and facilitate surgical resec- To overcome the technical challenges of complete
tion. In this perspective, a multidisciplinary deci- resection with accurate cardiac reconstruction,
sion-making approach relative to the overall particularly of left-sided tumors with posterior
therapeutic management is mandatory. extension, a technique of cardiac explantation,
Based on the surgical approach and clinical ex vivo tumor resection with cardiac reconstruc-
behavior, cardiac sarcomas can be classified as tion, and cardiac reimplantation—cardiac
autotransplantation—has been utilized [36–38, effusion which may contain masses comprising
77, 78, 83]. Surgical outcomes with cardiac auto- either cancer cells or blood clots and fibrin. The
transplantation are excellent in patients who do myocardium is the target of hematologous and/or
not require concurrent pneumonectomy [77]. retrograde lymphatic metastasis.
In selected cases of right ventricular tumors, a Cardiac metastases rarely are solitary and
right heart bypass (cavo-pulmonary anastomosis) nearly always produce multiple microscopic
has also been utilized as a palliation to prolong nests and discrete nodules of tumor cells [8].
survival [11–14, 33, 42–48]. Clinical symptoms are quite rare and mainly
The role of orthotopic cardiac transplantation related to pericardial effusion or cardiac tampon-
in the management of locally advanced non-met- ade. Arrhythmias, conduction block, and conges-
astatic cardiac tumors appears to be limited. tive heart failure have been occasionally reported
Indeed, it has been shown that about two-thirds [87–89].
of the so treated patients die of local recurrence Priority is given to the management of the pri-
or distant metastases within a year. Nevertheless, mary focus of the disease and the cardiovascular
about 25% of the patients managed by orthotopic complications that are manifested [28]. Surgical
cardiac transplantation have a mean survival of therapy is limited to relieve the recurrent pericar-
more than 2 years without recurrent disease [44– dial effusions or, occasionally, cardiac tamponade
46, 48, 78, 84]. The overall poor availability of (subxiphoid pericardiotomy, pericardial window)
donors however represent another important lim- [90]. In most instances, these patients have wide-
itation to the role of orthotopic cardiac transplan- spread disease with limited life expectancies.
tation in this cohort of patients. Abdominal and pelvic tumors (renal, hepatic,
Despite a good local control often achievable adrenal, uterine) on occasion may involve the
with surgery, postoperative adjuvant therapy is inferior vena cava, with an intraluminal throm-
recommended to all patients. Indeed, long-term botic extension to the right atrium. Renal cell
survival is frequently poor due to metastatic tumor cancer represents 1–3% of all visceral cancers
recurrence. This is particularly true in case of and 85–90% of malignant kidney tumors and is
incomplete tumor resection [77, 78, 82, 85, 86]. most frequently responsible for this phenomenon
(4–10% of all patients) (Fig. 10.13a, b) [91, 92].
Clinical symptoms are often few and nonspecific
Secondary Metastatic Cardiac Tumors and related to the progressive obstruction of the
inferior vena cava (ascites, peripheral edema)
Metastatic cardiac tumors are far more frequent and/or to the presence of an abdominal mass.
(approximately from 30- to 40-fold) than primary CT-scan and/or MRI are used to study the pri-
tumors of the heart. Although almost every type mary focus of the disease, while two-dimensional
of malignant tumor has the potential to reach the echocardiography and in some instances perfu-
heart, they usually arise from melanomas, lung, sion lung scintigraphy are utilized to evaluate car-
breast, and renal cancer, as well as lymphomas. diopulmonary involvement. Radiation and
Metastases may originate from blood dissemina- chemotherapy are not effective in relieving the
tion via coronary arteries (melanoma, sarcoma, obstruction of blood flow. However, if the kidney
bronchogenic carcinoma) or lymphatic channels can be fully removed, as well as the tail of tumor
of cancer cells, direct extension via adjacent tis- thrombus, survival can approach 75% at 5 years
sues (lung, breast, esophageal, and thymic [91, 92]. Surgical intervention, in the absence of
tumors), or propagation via the superior or the metastatic spread, besides to remove the primary
subdiaphragmatic vena cava to the right atrium focus of the disease, including the thrombus in the
(liver, kidney tumors) (Fig. 10.13a, b). The peri- inferior vena cava, the adjacent lymphatic struc-
cardium is most often affected by direct exten- tures, and, eventually, the involved caval wall,
sion of thoracic cancer, resulting in pericardial aims to prevent potentially massive pulmonary
Fig. 10.13 (a) CT evidence of a right renal cell cancer Intraoperative view. Tumor extension (T-ex) into the right
(RCC) with neoplastic extension into the inferior vena atrium through the inferior vena cava (IVC), attached to
cava (IVC) and right atrium (RA) [level IV cavoatrial the tricuspid valve apparatus (TV ap). Specimen after
tumor thrombus (insert diagram)]; RV right ventricle. (b) excision (insert)
embolism related to the fragmentation of the References

neoplastic tissue and/or thrombus. Renal cell
tumors with atrial extension typically are 1. Columbus MR. De Re Anatomica, Liber XV. Venice:
approached with abdominal dissection to ensure N Bevilacque, 1559. p. 269.
full resectability of the renal tumor. Depending on 2. Moes RJ, O’Malley CD. Realdo Colombo: on those
things rarely found in anatomy. Bull Hist Med.
the proximal extension of the tumor thrombus dif- 1960;34:508.
ferent surgical approaches have been recom- 3. Burns A. Observations of some of the most frequent
mended. In type III and IV disease, the exposure and important diseases of the heart. London: James
and isolation of the inferior vena cava are more Muirhead; 1809.
4. Goldberg HP, Glenn F, Dotter CT, Steinberg I.
extensive, requiring liver mobilization and some- Myxoma of the left atrium: diagnosis made during life
times an associated median sternotomy with or with operative and postmortem findings. Circulation.
without the use of cardiopulmonary bypass and, 1952;6:762.
in some circumstances, deep hypothermic circu- 5. Barnes AR, Beaver DC, Snell AMP. Primary sarcoma
of the heart: report of a case with electrocardiographic
latory arrest (DHCA) to improve exposure. and pathological studies. Am Heart J. 1934;9:480.
It is now accepted that neoplastic extension 6. Beck CS. An intrapericardial teratoma and tumor of
into the inferior vena cava is not a prognostically the heart: Both removed operatively. Ann Surg.
determining factor [92]. With no perinephric fat 1942;116:161.
7. Mauer ER. Successful removal of tumor of the heart.
or lymph nodal involvement, it has been observed J Thorac Surg. 1952;3:479.
that the patients who undergo tumor excision 8. Walkes JC, Smythe WR, Reardon MJ. Cardiac neo-
with a radical nephrectomy and inferior vena plasms. In: Cohn LH, editor. Cardiac surgery in the
cava thrombectomy have an overall and cancer- adult. 3rd ed. New York, NY: McGraw-Hill; 2008.
p. 1479–509.
specific 5-year survival of 30–72%, with an oper- 9. McAllister HA Jr, Fenoglio JJ Jr: Tumors of the car-
ative mortality of 2.7–13% and an immediate diovascular system. In: Atlas of tumor pathology.
palliation of symptoms of obstructive tumors Washington DC: Armed Forces Institute of Pathology,
[93–95]. 1978 (fas. 15).
10. Smith C. Tumors of the heart. Arch Pathol Lab Med. 26. Singh RN, Burkholder JA, Magovern GJ. Coronary
1986;110:371–4. arteriography as an aid in left atrial myxoma diagno-
11. Butany J, Nair V, Naseemudin A, Nair GM, Catton C, sis. Cardiovasc Intervent Radiol. 1984;7:40–3.
Yau T. Cardiac tumors: diagnosis and management. 27. Jurkovich D, de Marchena E, Bilsker M, Fierro-Renoy
Lancet Oncol. 2005;6:219–28. C, Temple D, Garcia H. Primary cardiac lymphoma
12. Travis WD, Brambilla E, Muller-Hermelink H, diagnosed by percutaneous intracardiac biopsy with
Harris CC. Pathology and genetics of tumors of the combined fluoroscopic and transesophageal echocar-
lung, pleura, thymus and heart. Lyon: IARC Press; diographic imaging. Cathet Cardiovasc Intervent.
2004. 2000;50:226–33.
13. Shapiro LM. Cardiac tumours: diagnosis and manage- 28. Paraskevaidis I, Michalakeas C, Papadopoulos C,
ment. Heart. 2001;85:218–22. Anastasiou-Nana M. Cardiac tumors ISRN oncology
14. Sarjeant JM, Butany J, Cusimano RJ. Cancer of the 2011;2011:208929.
heart: epidemiology and management of primary 29. Bahnson HT, Newman EV. Diagnosis and surgical
tumors and metastases. Am J Cardiovasc Drugs. removal of intracavitary myxoma of the right atrium.
2003;3:407–21. Bull Johns Hopkins Hosp. 1953;93:150–63.
15. Asch FM, Bieganski SP, Panza JA, Weissman NJ. 30. Crafoord C. Discussion on mitral stenosis and mitral
Real-time 3-dimensional echocardiography evalua- insufficiency. In: Lam CR, editor. Proceeding of the
tion of intracardiac masses. Echocardiography. international symposium on cardiovascular surgery,
2006;23:118–24. Henry Ford Hospital Philadelphia: WB Saunders,
16. Abramowitz Y, Hiller N, Perlman G, Admon D, Beeri 1955. p. 202.
R, Chajek-Shaul T, Leibowitz D. The diagnosis of pri- 31. Kay JH, Anderson RM, Meihaus J, Lewis R, Magidson
mary cardiac lymphoma by right heart catheterization O, Bernstein S. Surgical removal of an intracavitary
and biopsy using fluoroscopic and transthoracic left ventricular myxoma. Circulation. 1959;20:88–96.
echocardiographic guidance. Int J Cardiol. 32. Malm JR, Bowman FO, Henry JB. left atrial myxoma
2007;118:39–40. associated with an ASD. J Thorac Cardiovasc Surg.
17. Engberding R, Daniel WG, Erbel R, Kasper W, 1963;45:490.
Lestuzzi C, Curtius JM, Sutherland GR, Lambertz H, 33. Stiller B, Hetzer R, Meyer R, Dittrich S, Pees C,
von Hehn A, Lesbre JP. Diagnosis of heart tumours by Alexi-Meskishvili V, Lange PE. Primary cardiac
transoesophageal echocardiography: a multicentre tumors: when is surgery necessary? Eur J Cardiothorac
study in 154 patients. European Cooperative Study Surg. 2001;20:1002–6.
Group. Eur Heart J. 1993;14:1223–8. 34. Cusimano RJ. Surgical management of cardiac
18. Tan CN, Fraser AG, Tan CN, Fraser AG. tumors. Semin Diagn Pathol. 2008;25:76–81.
Transesophageal echocardiography and cardiovascu- 35. ElBardissi AW, Dearani JA, Daly RC, Mullany CJ,
lar sources of embolism. Anesthesiology. Orszulak TA, Puga FJ, Schaff HV. Survival after
2007;107:333–46. resection of primary cardiac tumors: a 48-year experi-
19. Restrepo CS, Largoza A, Lemos DF, Diethelm L, ence. Circulation. 2008;118:S7–15.
Koshy P, Castello P, Gomez R, Moncada R, Pandit M. 36. Thomas CR, Johnson GW, Stoddard MF, Clifford S.
CT and MR imaging findings of benign cardiac Primary malignant cardiac tumors: update 1992. Med
tumors. Curr Probl Diagn Radiol. 2005;34:12–21. Pediatr Oncol. 1992;20:519–31.
20. Araoz PA, Mulvagh SL, Tazelaar HD, Julsrud PR, 37. Reardon MJ, DeFelice CA, Sheinbaum R, Baldwin JC.
Breen JF. CT and MR imaging of benign primary car- Cardiac autotransplant for surgical treatment of a malig-
diac neoplasms with echocardiographic correlation. nant neoplasm. Ann Thorac Surg. 1999;67:1793–5.
Radiographics. 2000;20:1303–19. 38. Reardon MJ, Malaisrie SC, Walkes JC, Vaporciyan AA,
21. van Beek EJR, Stolpen AH, Khanna G, Thompson Rice DC, Smythe WR, DeFelice CA, Wojciechowski
BH. CT and MRI of pericardiac and cardiac neoplas- ZJ. Cardiac autotransplantation for primary cardiac
tic disease. Cancer Imaging. 2007;7:19–26. tumors. Ann Thorac Surg. 2006;82:645–50.
22. Sparrow PJ, Kurian JB, Jones TR, Sivananthan MU. 39. Attum AA, Johnson GS, Masri Z, Girardet R, Lansing
MR imaging of cardiac tumors. Radiographics. AM. Malignant clinical behavior of cardiac myxomas
2005;25:1255–76. and “myxoid imitators”. Ann Thorac Surg.
23. O’Donnel DH, Abbara S, Chaithiraphan V, Yared K, 1987;44:217–22.
Killeen RP, Cury RC, Dodd JD. Cardiac tumors: opti- 40. Read RC, White HJ, Murphy ML, Williams D, Sun CN,
mal cardiac MR sequences and spectrum of imaging Flanagan WH. The malignant potentiality of left atrial
appearances. AJR AmJ Roentgenol. 2009;193:377–87. myxoma. J Thorac Cardiovasc Surg. 1974;68:857–68.
24. Fueredi GA, Knechtges TE, Czarnecki DJ. Coronary 41. Schmitz C, Weinreich S, White J, Oengoeren I,
angiography in atrial myxoma: findings in nine cases. Schneider R, Schneider D, Speth I, Pohl C, Welz A.
Am J Roentgenol. 1989;152:737–8. Can particulate extraction from the ascending aorta
25. Kumar SP, Kaul S, Saha PK, Miller MJ. Images in reduce neurologic injury in cardiac surgery ? J Thorac
cardiology. Angiographic appearance of “tumour Cardiovasc Surg. 2003;126:1829–38.
blush” produced by a large right atrial myxoma. Heart. 42. Bakaeen FG, Reardon MJ, Coselli JS, Miller CC,
2006;92:751. Howell JF, Latrie GM, Espada R, Ramchandani MK,
Noon GP, Weilbaecher DG, DeBakey ME. Surgical 58. Gulmez O, Pehlivanoglu S, Turkoz R, Demiralay E,
outcome in 85 patients with primary cardiac tumors. Gumus B. Lipoma of the right atrium. J Clin
Am J Surg. 2003;186:641–7. Ultrasound. 2009;37:185–8.
43. Aravot DJ, Banner NR, Madden B, Aranki S, 59. Breuer M, Wippermann J, Franke U, Wahlers T.
Khaghani A, Fitzgerald M, Radley-Smith R, Yacoub Lipomatous hypertrophy of the interatrial septum and
MH. Primary cardiac tumors: is there a place for car- upper right atrial inflow obstruction. Eur J Cardiothorac
diac transplantation? Eur J Cardiothorac Surg. Surg. 2002;22:1023–5.
1989;3:521–4. 60. Verberkmoes NJ, Kats S, Tan-Go I, Schönberger JP.
44. Goldstein DJ, Oz MC, Rose EA, Fisher P, Michler Resection of a lipomatous hypertrophic interatrial
RE. Experience with heart transplantation for cardiac septum involving the right ventricle. Interact
tumors. J Heart Lung Transplant. 1995;14:382–6. Cardiovasc Thorac Surg. 2007;6:654–7.
45. Gowdamarajan A, Michler RE. Therapy for primary 61. Gowda RM, Khan IA, Nair CK, Mehta NJ, Vasavada
cardiac tumors: is there a role for heart transplanta- BC, Sacchi TJ. Cardiac papillary fibroelastoma: a
tion? Curr Opin Cardiol. 2000;15:121–5. comprehensive analysis of 725 cases. Am Heart J.
46. Dietl CA. Successful Fontan-type operation for non- 2003;146:404–10.
resectable right ventricular tumor. Ann Thorac Surg. 62. Yoda M, Tanabe H, Kanou H, Sawada H, Suma H.
1990;5:814–6. Multiple papillary fibroelastomas in rare locations of
47. Calderon M, Galvan J, Negri V, Verdin R. Right ven- aortic valve and left ventricular outflow tract: a case
tricular bypass for palliation of cardiac sarcoma. Tex report. J Heart Valve Dis. 2009;18:575–7.
Heart Inst J. 1996;23:178–9. 63. Kobayashi Y, Saito S, Yamazaki K, Kurosawa H.
48. Hoffmeier A, Deiters S, Schmidt C, Tjan TD, Schmid Multiple papillary fibroelastoma in left ventricle asso-
C, Drees G, Fallenberg EM, Scheld HH. Radical ciated with obstructive hypertrophic cardiomyopathy.
resection of cardiac sarcoma. Thorac Cardiovasc Interact Cardiovasc Thorac Surg. 2009;9:921–2.
Surg. 2004;52:77–81. 64. Kumar TK, Kuehl K, Reyes C, Talwar S, Moulick A,
49. Bortolotti U, Maraglino G, Rubino M, Santini F, Jonas RA. Multiple papillary fibroelastomas of the
Mazzucco A, Milano A, Fasoli G, Livi U, Thiene G, heart. Ann Thorac Surg. 2009;88:e66–7.
Gallucci V. Surgical excision of intracardiac myxomas: a 65. de Visser RN, van Mieghem C, van Pelt NC, Weustink
20-year follow-up. Ann Thorac Surg. 1990;49:449–53. AC, Kerker JP, Galema TW. Papillary fibroelastoma
50. Ipek G, Erentug V, Bozbuga N, Polat A, Guler M, of the aortic valve and coronary artery disease visual-
Kirali K, Peker O, Balkanay M, Akinci E, Alp M, ized by 64-slice CT. Nat Clin Pract Cardiovasc Med.
Yakut C. Surgical management of cardiac myxoma. 2008;5:350–3.
J Card Surg. 2005;20:300–4. 66. Grandmougin D, Fayad G, Moukassa D, et al.
51. Tasoglu I, Tutun U, Lafci G, Hijaazi A, Yener U, Ulus Cardiac valve papillary fibroelastomas: clinical, his-
AY, Aksoyek A, Saritas A, Birincioglu L, Pac M, tological and immunohistochemical studies and a
Katircioglu F. Primary cardiac myxomas: clinical physiopathogenic hypothesis. J Heart Valve Dis.
experience and surgical results in 67 patients. J Card 2000;9:832.
Surg. 2009;24:256–9. 67. Araji OA, Gutierrez-Martin MA, Miranda N, Barquero
52. Bakir I, Van Vaerenberg G, Deshpande R, Coddens J, JM. Video-assisted cardioscopy for removal of pri-
Vanermen H. Right atrial tumor: a contraindication mary left ventricular fibroma. Interact Cardiovasc
to minimally invasive surgery? Innovations. Thorac Surg. 2010 Feb;10:344–5.
2009;4:39–42. 68. Agarwala BN, Starr JP, Walker E, Bacha EA. Surgical
53. Uzun O, Wilson DG, Vujanic GM, Parsons JM, De issues in giant right ventricular fibroma. Ann Thorac
Giovanni JV. Cardiac tumours in children. Orphanet Surg. 2004;78:328–30.
J Rare Dis. 2007;2:11–25. 69. Valente M, Cocco P, Thiene G, Casula R, Poletti A,
54. Wu KH, Mo XM, Liu YL. Clinical analysis and surgi- Milanesi O, Fasoli G, Livi U. Cardiac fibroma and
cal results of cardiac myxoma in pediatric patients. heart transplantation. J Thorac Cardiovasc Surg.
J Surg Oncol. 2009;99:48–50. 1993;106:1208–12.
55. Actis Dato GM, De Benedictis M, Actis Dato A Jr, 70. Waller BR, Bradley SM, Crumbley 3rd AJ, Wiles HB,
Ricci A, Sommariva L, De Paulis R. Long-term McQuinn TC, Bennett AT. Cardiac fibroma in an
follow-up of cardiac myxomas (7–31 years). infant: single ventricle palliation as a bridge to heart
J Cardiovasc Surg. 1993;34:141–143. transplantation. Ann Thorac Surg. 2003;75:1306–8.
56. Acebo E, Val-Bernal JF, Gómez-Román JJ, Revuelta 71. Garson Jr A, Smith Jr RT, Moak JP, Kearney DL,
JM. Clinicopathologic study and DNA analysis of 37 Hawkins EP, Titus JL. Incessant ventricular tachycar-
cardiac myxomas: a 28-year experience. Chest. dia in infants: myocardial hamartomas and surgical
2003;123:1379–85. cure. J Am Coll Cardiol. 1987;10:619–26.
57. Yokomuro H, Yoshihara K, Watanabe Y, Shiono N, 72. Nicks R. Hamartoma of the right ventricle. J Thorac
Koyama N, Takanashi Y. The variations in the immu- Cardiovasc Surg. 1964;47:762.
nologic features and interleukin-6 levels for the surgi- 73. Geva T, Santini F, Pear W, Driscoll SG, Van Praagh R.
cal treatment of cardiac myxomas. Surg Today. Cardiac rhabdomyoma. Rare cause of fetal death.
2007;37:750–3. Chest. 1991;99:139–41.
74. Degueldre SC, Chockalingam P, Mivelaz Y, Di 85. Poole GV, Meredith JW, Breyer RH, Mills SA.
Bernardo S, Pfammatter JP, Barrea C, Sekarski N, Surgical implications in malignant cardiac disease.
Jeannet PY, Fouron JC, Vial Y, Meijboom EJ. Ann Thorac Surg. 1983;36:484–9.
Considerations for prenatal counselling of patients with 86. Janigan DT, Husain A, Robinson NA. Cardiac
cardiac rhabdomyomas based on their cardiac and neu- angiosarcomas: a review and case report. Cancer.
rologic outcomes. Cardiol Young. 2010;20:18–24. 1986;57:852–91.
75. Padalino MA, Basso C, Milanesi O, Vida VL, Moreolo 87. Hanfling SM. Metastatic cancer to the heart: review of
GS, Thiene G, Stellin G. Surgically treated primary the literature and report of 127 cases. Circulation.
cardiac tumors in early infancy and childhood. 1960;2:474–83.
J Thorac Cardiovasc Surg. 2005;129:1358–63. 88. Weinberg BA, Conces Jr DJ, Waller BF. Cardiac man-
76. Santini F, Innocente F, Gilioli E, Rossi A, Ferrara A, ifestation of noncardiac tumors, part I: direct effects.
Brunelli M, Faggian G, Mazzucco A. Primary bi-atrial Clin Cardiol. 1989;12:289–96.
Burkitt lymphoma with severe inflow impairment in 89. Chiles C, Woodard PK, Gutierrez FR, Link KM.
an immunocompetent patient. Cardiovasc Pathol. Metastatic involvement of the heart and pericardium:
2009;18:123–5. CT and MR imaging. Radiographics. 2001;21:
77. Blackmon SH, Patel A, Reardon MJ. Management of 439–49.
primary cardiac sarcomas. Expert Rev Cardiovasc 90. Lestuzzi C, Bearz A, Lafaras C, Gralec R, Cervesato
Ther. 2008;6:1217–22. E, Tomkowski W, DeBiasio M, Viel E, Bishiniotis T,
78. Putnam JB, Sweeney MS, Colon R, Lanza LA, Frazier Platogiannis DN, Buonadonna A, Tartuferi L, Piazza
OH, Cooley DA. Primary cardiac sarcomas. Ann R, Tumolo S, Berretta M, Santini F, Imazio M.
Thorac Surg. 1991;51:906–10. Neoplastic pericardial disease in lung cancer: impact
79. Neragi-Miandoab S, Kim J, Vlahakes GJ. Malignant on outcomes of different treatment strategies. A mul-
tumours of the heart: a review of tumour type, diagno- ticenter study. Lung Cancer. 2011;72:340–7.
sis and therapy. Clin Oncol. 2007;19:748–56. 91. Prager RL, Dean R, Turner B. Surgical approach to
80. Gupta A. Primary cardiac sarcomas. Expert Rev intracardial renal cell carcinoma. Ann Thorac Surg.
Cardiovasc Ther. 2008;6:1295–7. 1982;33:74–7.
81. Park BJ, Bacchetta M, Bains MS, Downey RJ, Flores 92. Chiappini B, Savini C, Marinelli G, Suarez SM, Di
R, Rusch VW, Girardi LN. Surgical management of Eusanio M, Fiorani V, Pierangeli A. Cavoatrial tumor
thoracic malignancies invading the heart or great ves- thrombus: single-stage surgical approach with pro-
sels. Ann Thorac Surg. 2004;78:1024–30. found hypothermia and circulatory arrest, including a
82. Bakaeen FG, Jaroszewski DE, Rice DC, Walsh GL, review of the literature. J Thorac Cardiovasc Surg.
Vaporciyan AA, Swisher SS, Benjamin R, Blackmon 2002;124:684–8.
S, Reardon MJ. Outcomes after surgical resection of 93. Posacioglu H, Ayik MF, Zeytunlu M, Amanvermez D,
cardiac sarcoma in the multimodality treatment era. Engin C, Apaydin AZ. Management of renal cell car-
J Thorac Cardiovasc Surg. 2009;137:1454–60. cinoma with intracardiac extension. J Card Surg.
83. Blackmon SH, Patel AR, Bruckner BA, Beyer EA, 2008;23:754–8.
Rice DC, Vaporciyan AA, Wojciechowski Z, Correa 94. Kalkat MS, Abedin A, Rooney S, Doherty A, Faroqui
AM, Reardon MJ. Cardiac autotransplantation for M, Wallace M, Graham TR. Renal tumours with cavo-
malignant or complex primary left-heart tumors. Tex atrial extension: surgical management and outcome.
Heart Inst J. 2008;35:296–300. Interact Cardiovasc Thorac Surg. 2008;7:981–5.
84. Crespo MG, Pulpon LA, Pradas G, Serrano S, Segovia 95. Yazici S, Inci K, Bilen CY, Gudeloglu A, Akdogan
J, Vegazo I, Salas C, Espana P, Silva L, Burgos R. B, Ertoy D, Kaynaroglu V, Demircin M, Ozen H.
Heart transplantation for cardiac angiosarcoma: Renal cell carcinoma with inferior vena cava throm-
should its indication be questioned? J Heart Lung bus: The Hacettepe experience. Urol Oncol.
Transplant. 1993;12:527–30. 2010;28:603–9.
Cardiac Metastases
11
Furio Silvestri, Gianfranco Sinagra,
and Rossana Bussani
related trends [5–15]. The relatively low rate of

Introduction cardiac metastases has been ascribed to the con-
tractile strength of the heart, the specific metabo-
Primary and secondary tumors of the heart are lism of the myocardium, the velocity of the
one of the least addressed and understood sub- coronary blood flow, and the lymphatic network
jects in oncology and there have been a few sys- that drains from the heart [3].
tematic studies relating to this subject [1–3]. Although there are no known specifically car-
Although primary heart tumors are extremely diotropic malignant neoplasms, some neverthe-
rare, with a rate of incidence between 0.001 and less involve the heart with a higher frequency
0.28% in various autopsy studies [2], the heart than others, such as melanoma and mediastinal
can be the target of metastases from any extracar- primary tumors. The likelihood of tumoral diffu-
diac malignant neoplasm able to spread to distant sion to the heart depends therefore on several
sites. Apart from this, the issue of cardiac metas- factors i.e., the specific biological potential of
tases has a significant clinical impact as cardiac the main tumor, its location (and its proximity to
metastases can cause alterations in cardiac func- the heart), and the contractile and drainage
tion. Any sign of cardiac dysfunction in a patient capacity of the myocardium.
affected by cancer should alert clinicians to the Therefore, it is logical to assume that in most
possibility of metastases [4]. One might also gen- cases neoplasms that have a generalised second-
erally add that when a patient with no clinical ary diffusion involve the heart.
history develops a cardiac dysfunction with no
apparent cause, clinicians should take into con-
sideration the possibility of a cardiac metastasis Clinical Manifestations
amongst the various hypotheses.
The rates of cardiac metastasis reported in the As previously mentioned, cardiac metastasis can
literature are highly variable (Table 11.1) and, at be the first or even the only sign of a clinically
least in our experience, have no specific time- undiagnosed malignant neoplasm. Generally, if a
focal myocardial metastasis does not give a clear
symptomatic clinical picture, more extensive
F. Silvestri, M.D. • R. Bussani, M.D. (*) involvement of the pericardium or other cardiac
Department of Pathologic Anatomy, University of Trieste
areas can determine dramatic clinical situations
Medical School, Cattinara Hospital, Trieste, Italy
e-mail: bussani@univ.trieste.it causing clinical emergencies. Symptoms differ
according to the areas involved. Meta-tumoral
G. Sinagra, M.D.
Cardiovascular Department, University of Trieste pericardial effusions and cardiac masses can be
Medical School, Cattinara Hospital, Trieste, Italy easily detected by transthoracic and transesophageal
152 F. Silvestri et al.
Table 11.1 Overview of the literature well as the direct toxic effect to the myocar-
Neoplasms Cardiac metastases dium from infiltration of the tumor. Although
Author N. N. (%) not frequent, a myocardial infarction can occur
Walther [5] 2,027 46 (2.3) and can be due to several factors, such as a
Willis [6] 342 17 (4.9) neoplasm-induced embolus in the coronary
Hanfling [7] 694 127 (18.3) tree, a perivascular tumoral invasion, or an
Berge & Sievers [8] 2,595 122 (4.7) extrinsic compression by a severe meta-tumoral
Kline [9] 716 61 (8.5) pericardial effusion.
Karwinski & 2,564 130 (5.1)
• Metastases to the endocardium or intracavi-
Svendsen [10]
Mukai et al. [11]. 6,240 953 (15.0)
tary lesions.
Manojlovic [12] 477 39 (8.2) Some tumors can spread along the inferior
MacGee [13] 1,311 57 (4.3) vena cava reaching the right atrium and pro-
Silvestri et al. [14] 1,928 162 (8.4) ducing an intracavitary lesion, leading some-
Bussani et al. [15] 7,289 662 (9.1) times to obstruction. The most typical of these
tumors are the carcinoma of the kidney and
the hepatocellular carcinoma. These types of
ultrasound imaging, computerised tomography lesions can sometimes become so invasive
scan, high-resolution CT, and magnetic reso- that they obliterate completely the chamber
nance [16]. The cytological analysis of the peri- and block the movement of the tricuspid valve,
cardial effusion also may allow us to detect and resulting in a clinical pattern similar to peri-
characterize the neoplastic cells. cardial constriction or restrictive myocardial
• Pericardial metastases disease. In addition, it is also possible that the
A pericardial effusion, often with a haemor- metastatic mass can become eroded and shed
rhagic pattern, is frequently the first sign of a small neoplastic emboli in the pulmonary arte-
metastatic cardiac involvement [17]. The rial system.
effusion, often of conspicuous proportions, Another risk is the formation of neoplastic
can cause an increase of the central venous thrombi within the pectinate muscles of the right
pressure, a paradoxical pulse, low QRS volt- atrium or the trabeculae of the right ventricle, the
ages, and right atrioventricular diastolic col- latter generally with no clinical manifestations.
lapse. Should pulseless electrical activity Neoplastic thrombi are also possible in the left
occur, a pericardiocentesis must be performed atrium, following tumoral embolism through the
immediately. pulmonary veins, generally in patients with lung
• Myocardial metastases carcinoma. Large thrombi can block the mitral
In the case of secondary cardiac intramural valve.
localisations, the clinical picture is obviously
proportional to the degree of myocardial
infiltration or, in any case, related to the site of Metastatic Pathways to the heart
parietal infiltration. Typical manifestations are
the following: more or less significant arrhyth- Cardiac metastases can affect, also in combina-
mias such as atrial flutter or fibrillation, prema- tion, the pericardium, the epicardium, the myo-
ture beats or ventricular arrhythmias, conduction cardium, the endocardium, and the cardiac
disturbances, and complete atrioventricular chambers, or sometimes rapidly develop intrac-
block, especially when the conduction system avitary neoplastic thrombi. Tumors can spread to
has been infiltrated. Whenever there is a wide- the heart through four possible pathways, i.e., by
spread ventricular involvement, the clinical direct extension, through the bloodstream,
pattern may include congestive heart failure. through the lymphatic system, and by intracavi-
One can add to this the possible damage to the tary diffusion through either the inferior vena
myocardium from the antineoplastic drugs, as cava or the pulmonary veins.
11 Cardiac Metastases 153
Obstruction to the lymphatic flow causes

Pericardial Involvement multiple alterations that make the lymphatic
drainage more complex, if not impossible,
The main metastatic pathways are the direct inva- increasing tissue damage. For example, a direct
sion from intrathoracic neoplasms, a retrograde relationship between coronary perfusion and
lymphatic spread through tracheal or bronchomedi- lymphatic flow has been described [20].
astinal lymphatic channels, or secondary spread of Experimental studies have shown that no contrast
metastases from the myocardium and epicardium. medium is absorbed by the lymphatics in the
absence of coronary perfusion, while, as the cor-
onary flow restores, the absorption and lymphatic
Epicardial or Myocardial Metastatic drainage are re-established and become visible
Involvement once again.
If intramural lymphatics are obstructed by
The metastatic routes are a retrograde lym- neoplastic emboli, lymph will stagnate in the
phatic spread through tracheal or bronchomedi- myocardial areas upstream of the obstruction,
astinal channels, as extensions secondary to an and the lymphatic drainage from the endocar-
already metastasised pericardium or through dium to the epicardium will be partially or totally
the bloodstream. inhibited. This causes tissue damage, due to both
lymph stasis and inadequate drainage thus favou-
ing increased proliferation of neoplastic cells in
Endocardial Involvement the undrained regions. As a result of increased
pressure, the lymphatic vessel wall may also
The spread routes are a direct haematogenous break, leading to interstitial tumor spread.
dissemination to the cardiac chambers followed Myocardial contraction has two effects, one
by intracavitary lodging, or the extension of the hindering the metastatic process, and the other
metastases from the myocardium. promoting it. Cardiac contraction, as a matter of
There is a subtle interactive relationship fact, on one hand hinders the spreading of intra-
between the haematic and lymphatic network of mural neoplastic metastases by facilitating the
the heart. The heart has a three-tiered lymphatic lymphohaematic drainage and therefore displac-
network: the subepicardial, the myocardial, and ing any cardiac neoplastic emboli; on the other
the subendocardial nets. Drainage of the lymphat- hand, it helps the diffusion of tumoral cells along
ics forms a major trunk that drains the whole heart the epicardial surface.
and rests against the anterior side of the pulmo- The key event leading to the diffusion of
nary artery. Multiple lymphatic channels drain the metastases is, therefore, the blockage of the com-
lymph from the heart to the mediastinum. There is mon lymphatic node by neoplastic cells coming
also a common cardiac and pulmonary lymphatic from metastasised lymph nodes of the mediasti-
duct draining directly into the mediastinum [18]. num. This causes the slowing down of the lymph
The subepicardial lymphatic plexus is formed flow in the myocardium and the retrograde migra-
by a net of capillaries and drainage ducts [19]. tion and proliferation of neoplastic cells towards
During diastole, the blood pressure in the ventri- the epicardium [21].
cles drives the lymphatic drainage from the endo- Once the neoplastic cells have reached and col-
cardial net to the myocardial one. During systole, onised the epicardium, neoplastic emboli can pen-
cardiac contractions drive lymph from the myo- etrate the intramural lymphatics as the lymphatic
cardial lymphatics to the subepicardial ones. The vessels follow closely the arterial ones. The dam-
pressure of the dilated heart against the pericar- age to the myocardium caused by the stasis of the
dium at the end of diastole drains lymph from the lymph flow as well as by the toxic effect of both
subepicardial net into the main lymphatic trunk the tumor and chemotherapy can further reduce
that emerges from the heart. myocardial contractility that in its turn further
Table 11.2 Malignant tumors and cardiac metastases at autopsy,

Department of Pathologic Anatomy, University of Trieste, Italy
(1994 → 2008)
Autopsy, N. Neoplasms Cardiac metastases
N % N %
Males 12,559 5,777 46.0 535 9.0
Females 13,072 4,186 32.0 370 9.0
Total 25,631 9,963 39.0 905 9.0
Fig. 11.1 Frequency of cardiac metastases from different type of primary malignant neoplasms
impairs the drainage of the lymph and facilitates in the time frame between 1994 and 2008. In 9,963
the penetration and proliferation of the tumor in cases, one or more malignant neoplasms were found
the myocardium. (39% of total autopsy studies). Cardiac metastases
were found in 905 cases (9% of all malignant
tumors) (Table 11.2). While there was a gender dif-
Epidemiology of Cardiac Metastases ference in the rate of malignant tumors, 46% in men
and 32% in women, there was no difference as far
Few papers have been published in the literature as cardiac metastases were concerned.
on cardiac metastases, possibly because of the The incidence of primary tumors was decreas-
international trend to perform fewer postmortem ing with age (52% in patients aged £64 years vs.
examinations [14]. 26.7% in patients >85) as well as the incidence of
In our Department of Pathologic Anatomy, cardiac metastases (16.7% in the younger cases
University of Trieste, Italy, in spite of a reduced and 4% in the over 85). This pattern was evident
global autopsy rate in the last years, the postmor- for every tumor detected and is probably due to
tem examinations of in-hospital deceased remains the less aggressive biological characteristics of
consistently above 60%. tumors in the elderly.
In our Department, 25,631 postmortem studies The tumors with the highest rate of heart
were performed (12,559 men and 13,072 women) metastases were the following (Fig. 11.1):
Fig. 11.2 Location of cardiac metastases by type of primary malignant neoplasm
pleural mesothelioma (48.4%), melanoma metastases involved the pericardium [69.4%],

(27.8%), lung adenocarcinoma (21.0%), undif- one-third the epicardium [34.2%] or the myocar-
ferentiated carcinoma of the lung (19.5%), lung dium [31.8%], and only 5% the endocardium.
squamous cell carcinoma (18.2%), and breast The tumors with the highest pericardial involve-
carcinoma (15.5%). High rates of cardiac ment were (Fig. 11.2) mesothelioma, lung ade-
metastases have also been observed in ovarian nocarcinoma, ovary, stomach, and prostate
carcinomas (10.3%), lymphomyeloprolifera- carcinoma. The epicardium was more frequently
tive neoplasms (9.4%), bronchioalveolar involved by melanoma, lung squamous cell car-
(9.8%), gastric (8.0%), renal (7.3%), and pan- cinoma, and bronchioalveolar carcinoma. The
creatic (6.4%) carcinomas. myocardium was more often the target of mela-
When taking into consideration only tumors noma and lymphomyeloproliferative processes,
with multiple distant metastases, the incidence of whereas the endocardium was particularly
cardiac involvement significantly increases reach- involved by melanoma, kidney and hepatic
ing a global rate of 14.2%. The tumors that show a carcinoma.
higher cardiac metastatic rate are melanoma, bron- While there was no significant age difference
chioalveolar carcinoma, and renal carcinoma. between the patients presenting heart metastases
With the exception of mesothelioma (57.3% from mesothelioma or lung or breast carcinoma
men vs. 30% women), there was no gender and those with metastases in other sites, this was
difference. not the case for leukemic or lymphomatous pro-
In our series, the heart was the only target of cesses, prostatic or ovarian neoplasms, cancers of
metastasis in 14 out of 905 cases. They were the stomach or pancreas, where the age of the
respectively five cases of lung squamous cell patients with heart metastases was significantly
carcinoma, three cases of breast carcinoma, two lower of that of patients who presented carcino-
lymphoma, one carcinoma of the oesophagus, mas spreading to different sites.
two pleural mesothelioma, and one carcinoma of As far as lung carcinomas, the rates of metas-
the kidney. About two-thirds of all cardiac tasis differed according to the specific histotype.
Adenocarcinoma spreads to the heart in 26%

of cases, squamous cell carcinoma in 23.4%, Morphological Aspects
undifferentiated carcinoma in 21.2%, and bron-
chioalveolar carcinoma in 17.4%. For all the lung Heart metastases can present a wide variety of
cancer histotypes, however, the most affected morphological aspects according to the type of
area was the pericardium (82.2% of adenocarci- tumor, its site, its spreading capacity, and the
nomas, 72.4% of squamous cell carcinoma, and manner of permeating the heart.
67.2% of undifferentiated carcinomas). The
remaining cardiac structures show proportionally
similar rates for the various histotypes, although Pericardial Metastases
we should highlight a certain preferential trend
for the epicardium from squamous cell carcinoma The neoplastic infiltration can be focal, diffuse,
(41.4%), while no cases of adenocarcinoma or massive, with or without metaneoplastic fibrin-
spreading to the endocardium were found. blood effusion (Fig. 11.3).
Fig. 11.3 Pericardial metastases usually present clini- roid carcinoma. (b) Massive tumoral infiltration of the
cally as pericardial effusion especially in diffuse and hae- pericardium by a lung adenocarcinoma. (c) Histology of
morrhagic forms. (a) Neoplastic infiltration of the extensive lymphatic colonisation by carcinomatous cells
pericardium by direct invasion by an undifferentiated thy- (same case)
Epicardial Metastases infiltrated areas followed by secondary epicardial

colonisation (usually a nodular infiltration), as
The neoplastic infiltration can present a micro- or well as from the lymphatic blockage (Fig. 11.5).
macronodular or diffuse aspect (Fig. 11.4). Also Spread to the epicardium may occur not only
in this case, the infiltration can originate from the through the lymphatic pathway (multifocal or
flaking of cancerous cells from pericardial- diffuse) but also through the bloodstream (in this
Fig. 11.4 Epicardial metastases. The neoplastic infiltration can present a micronodular (a, b) or a macronodular aspect
(c, d). Frequently the metastatic involvement presents a haemorrhagic pattern (e, f)
Fig. 11.5 (a) Flaking of neoplastic cells from pericardium to epicardium. (b) Lymphatics permeated with carcinoma-
tous cells. (c) Haemorrhagic pattern of epicardial metastatic involvement
case the pattern tends to be micro-focal, and is Metastatic cells can target the myocardium
often due to the neoplastic spread from intramu- following two routes, i.e., they can either prolifer-
ral colonised areas of the myocardium). ate and spread along the lymphatic channels that
When a diffuse carcinomatous spread occurs, run along the vessels from the epicardium into the
a tight yellow-whitish mesh of lymphatics same myocardium, or through the bloodstream.
permeated with neoplastic cells can be seen on Blood embolisation may result in lesions of
the epicardium. remarkable size, which can sometime compress
Another interesting pattern is that of the “wave the surrounding myocardium and cause secondary
front extension”. When there is an endolymphatic hypoperfusion. Should occlusive endocoronaric
epicardial involvement and the heart develops neoplastic emboli occur, overt intramural metane-
dysfunction for various reasons (coronary artery, oplastic infarctions may result. Intramural metas-
valvular, either due to the chemotherapy, or to the tases of the myocardium progressively increase in
same lymphatic stagnation), the contractility of size and can spread to both the epicardial and
the myocardium is further greatly reduced. As a endocardial components (Fig. 11.6). Neoplastic
consequence, both the lymphatic drainage and infiltration of the coronary sinus is extremely rare:
the arterial and venous blood flow are decreased, in this setting, the carcinomatous cells infiltrating
and the lymphatic structure is dilated allowing a the fatty tissue of the basal heart region invade the
wide homogeneous tumoral wave front progres- atrium and involve the coronary sinus, which has
sion from the epicardium to the myocardium. been occluded by a neoplastic thrombosis.
The pericardial effusion seen in neoplastic The neoplastic invasion secondary to lym-
peri-epicarditis is often characterized by a full- phoma almost always replaces the myocardium,
fledged haemorrhage. This is very likely due to with broad areas globally infiltrated by a homo-
both the damage of the thin capillary wall caused geneous white-greyish tissue, with the typical
by the release of inflammatory-related noxious “fish meat” pattern [28].
substances as well as by hyperdilation of the vas- In spite of the massive loss of contractile
cular lumen due to congestion. mass, cardiac symptoms can be absent or
aspecific [29]. In the few existing reports [30],
the myocardium seems mostly involved by non-
Myocardial Metastases Hodgkin’s lymphomas (78.3% vs. 66.7% of
Hodgkin’s lymphomas), whereas the pericar-
In our experience there has been no preferential dium is mostly affected in Hodgkin’s lympho-
involvement of a ventricular chamber from intra- mas. Echocardiography may reveal a thickened
mural invasion. There are, however, conflicting myocardium, an anomalous myocardial struc-
observations in the literature regarding ventricu- ture, and abnormal wall contractility.
lar involvement. According to some authors, the
right ventricle is particularly affected [3, 11, 22].
They attribute this to the low pressure in the Endocardial Metastases
chamber and to the decreased systolic function
of the ventricle, which facilitates the lodging of In the endocardium, the metastatic lesions are
metastases. In other studies, the left ventricle mainly located in the right atrium (Fig. 11.7c) or
seems to be the most affected [23–25], while ventricle. Left atrial or ventricular lesions are
other authors suggest that there is no preferen- relatively uncommon. The anchorage of neoplas-
tial metastatic involvement [26, 27]. In our tic cells to the right chambers endocardium is
series, both ventricular chambers and the inter- favoured by lower intracavitary pressure, by the
ventricular septum were affected as a result of a slower blood flow, and by the lower contractile
diffuse and non-preferential haematogenous strength, which are all typical of this regions.
spread. Furthermore, the neoplastic cells usually come
Fig. 11.6 Myocardial metastases. Multiple types and undifferentiated carcinoma of the lung. (d) Biventricular
extension of intramural metastatic lesions are shown. (a) lymphomatous invasion. (e) Metastatic cells spreading
Small metastases from a squamous esophageal carcinoma. along the lymphatic vessels, sometimes located near hae-
(b) Septal and ventricular metastases from a cutaneous matic vessels (f)
melanoma. (c) Extensive transmural infiltration by an
from the inferior vena cava (tumors of the kid- superficial erosion and fragmentation resulting in
ney, liver, and uterus) or superior one (thyroid pulmonary microembolism (Fig. 11.7a).
tumors), thus entering the right atrium first. Heart valves are an unusual target for metasta-
Macroscopically, small, multiple thrombotic/ ses [31, 32] which is probably due to two factors,
neoplastic intertrabecular formations are often i.e., the absence of vessels in the normal valvular
found in the right ventricle. At other times, large stroma and the continuous cusp motion. When
neoplastic thrombi can be found in the right valvular involvement occurs, the most likely pat-
atrium or right ventricle, where they can often tern is that of a neoplastic thrombotic endocardi-
cause haemodynamic obstruction and sometimes tis: thrombotic material mixed with neoplastic
Fig. 11.7 Endocardial metastases. (a) Multiple small the right atrium in a patient with hepatocellular carci-
metastatic lesions in the endocardium of the right ventri- noma. (d) Multiple, large metastatic nodules from a cuta-
cle from a squamous pharyngeal carcinoma. (b) Extensive neous melanoma in the right atrium; the lesions involve
metastasis from a renal carcinoma occupying the entire the sino-atrial node region too
ventricular chamber. (c) Massive neoplastic thrombosis of
elements superimpose upon an endocardium towards the determination of the origin of the
already damaged by hemodynamic and flogistic neoplastic cells. Another option is the histopatho-
factors. This is facilitated by a state of hyperco- logical assessment of pericardial biopsy speci-
agulation typical of many tumors [33, 34]. In our mens after thoracotomy [1].
experience of thousands of postmortem examina- Patients with a metastatic carcinoma of
tions, we found only one case of neoplastic unknown primary location represent a relatively
thrombotic endocarditis of the tricuspid valve in common clinical problem which requires very
a patient affected by a poorly differentiated folli- important management and therapeutic decisions
cular carcinoma of the thyroid [35]. in order to solve it [36].
One of the most frequent examples is that of
pericardial metastases from an adenocarcinoma.
The Clinical Diagnosis of Pericardial This tumor quite often has no histopathological
Metastases characteristic pointing to the anatomical location
of the primary tumor. Even though the most likely
As a metastatic pericardial effusion is often the chance is that of a metastasis from a lung carci-
first clinical sign of a malignant tumor in patients noma [37, 38], immunohistochemical markers
with no history of cancer, the cytodiagnostic should nevertheless be used to get the best pos-
analysis of the same effusion can be the first step sible indications of the origin of the tumor.
The first goal is to understand whether the No specific markers exist for breast carcinoma
tumor is a lung adenocarcinoma, a reactive either [40]. Besides morphological data, CK7
mesothelial proliferation, or an epithelial positivity and CK20 negativity, oestrogen and
mesothelioma. progestogen receptors can be used, and in the
From a histochemical point of view, mucicar- past few years the so-called “gross cystic disease
mine and periodic acid-Schiff stain with diastase fluid protein-15”, which seems to correlate
digestion are useful to characterise the cytoplas- significantly with this tumor.
mic mucin vacuoles, which are usually present, A number of specific immunohistochemical
in variable proportions, in adenocarcinomas, panels can now permit the exact classification in
while they are completely absent in mesothe- the case of pericardial metastases secondary to
lioma cells. In mesotheliomas, cytoplasmic various neoplasms, such as lymphoma (CD3,
hyaluronic acid is revealed by colloidal iron or CD20, CD10, CD15, CD30, etc.), melanoma
Alcian Blue. The most likely immunohistochem- (S100, HMB45), myeloma (light-chain immuno-
ical algorithm for lung adenocarcinoma is the globulins), testicular neoplasms (CD30, hCG,
following: peripheral or membrane keratin posi- CEA, alfa-feto protein) and those of the urothe-
tivity and TTF1 (“Thyroid Transcription Factor lial area (CK5-6, CK7, CK 20).
1”), BerEP4, leu-M1, and CK7 positivity. Immunohistochemical markers are also a fun-
Mesotheliomas, on the contrary, are always posi- damental tool in the diagnosis of cardiac spread
tive to keratins, but only to the cytoplasmic com- from sarcomas (keratin negative and positivity to
ponent, and to vimentin and calretin. specific mesenchymal line markers).
Unfortunately, as yet, there is no mesothe-
lioma-positive and adenocarcinoma-negative
immunohistochemical marker. The immunohis- References
tochemical diagnosis of mesothelioma can only
be reached by exclusion. 1. Virmani R. Tumors metastatic to the heart and peri-
cardium. In: Virmani R, Burke A, editors. Atlas of
The next step is to trace any other primary
tumor pathology. Tumors of the heart and great ves-
locations of adenocarcinomatous spread to the sels. 3rd Series, Fascicle 16. Washington, DC: AFIP;
heart. According to some authors, a specific panel 1995. p. 195–209.
of markers (BCA225, CEA, CA125, CA19-9) 2. McAllister Jr HA. Tumours of the heart and pericar-
dium. In: Silver MD, editor. Cardiovascular pathol-
could be fairly predictive for such neoplasms [39]
ogy, vol. 2. 2nd ed. New York, NY: Churchill
as colon, breast, lung, and ovarian carcinomas. Livingstone Inc; 1991. p. 1297–333.
However, the sensitivity of these immunopheno- 3. Prichard RW. Tumors of the heart: review of the sub-
types is quite low, as they are expressed in vary- ject and report of one hundred thirty-seven cases.
Arch Pathol. 1951;51:98–128.
ing rates by 32–39% of metastatic cells.
4. Wenger NK. Pericardial disease in the elderly.
Other markers can also be useful. For instance, Cardiovasc Clin. 1992;22:97–103.
lung carcinomas are CK7 positive and CK20 neg- 5. Walther HE. Krebsmetastasen. Basel: Benno Schwabe;
ative, whereas colon adenocarcinomas are CK7 1948. p. 37–42.
6. Willis RA. The spread of tumours in the human body,
negative. On the other hand, it is easy to confirm
vol. 3. 2nd ed. London: Butterworths; 1952. p. 42.
the thyroid or prostatic origin of a pericardial 7. Hanfling SM. Metastatic cancer to the heart. Review
metastasis as TTF1 and thyroglobulin can be of the literature and report of 127 cases. Circulation.
used for thyroid carcinomas and prostatic-specific 1960;22:474–83.
8. Berge T, Sievers J. Myocardial metastases. A patho-
antigen for the prostatic carcinomas.
logical and electrocardiographic study. Br Heart J.
Cell clusters originating from a metastasised 1968;30:383–90.
squamous cell lung carcinoma are usually CK5 9. Kline IK. Cardiac lymphatic involvement by meta-
positive and CK7, CK20 and TTF1 negative, static tumor. Cancer. 1972;29:799–808.
10. Karwinski B, Svendsen E. Trends in cardiac metasta-
whereas undifferentiated lung carcinomas are neg-
sis. APMIS. 1989;97:1018–24.
ative also for CK5 but positive for NSE (neuron- 11. Mukai K, Shinkai T, Tominaga K, Shimosato Y. The
specific enolase), cromogranine and calcitonin. incidence of secondary tumors of the heart and
pericardium: a 10-year study. Jpn J Clin Oncol. 28. Roberts WC, Glancy DL, De Vita Jr VT. Hodgkin’s
1988;18:195–201. disease, lymphosarcoma, reticulum cell sarcoma and
12. Manojlovic S. Metastatic carcinomas involving the mycosis fungoides. A study of 196 autopsy cases. Am
heart. Review of post-mortem examination. Zentralbl J Cardiol. 1968;22:85–107.
Allg Pathol Anat. 1990;136:657–61. 29. Meng Q, Lai H, Lima J, Tong W, Qian Y, Lai S.
13. MacGee W. Metastatic and invasive tumours involv- Echocardiographic and pathological characteristics of
ing the heart in a geriatric population: a necropsy cardiac metastasis in patients with lymphoma. Oncol
study. Virchows Arch A Pathol Anat Histopathol. Rep. 2002;9:85–8.
1991;419:183–9. 30. Moore JA, De Ran BP, Minor R, Arthur J, Fraker TD.
14. Silvestri F, Bussani R, Pavletic N, Mannone T. Transesophageal echocardiographic evaluation of
Metastases of the heart and pericardium. G Ital intracardiac lymphoma. Am Heart J. 1992;124:514–6.
Cardiol. 1997;27:1252–5. 31. Hallahan DE, Vogelzang NJ, Borow KM, Bostwick
15. Bussani R, De-Giorgio F, Abbate A, Silvestri F. DG, Simon MA. Cardiac metastases from soft-tissue
Cardiac metastases. J Clin Pathol. 2007;60:27–34. sarcomas. J Clin Oncol. 1986;4:1662–9.
16. Butany J, Naseemuddin A, Nair GM, Catton C, Yau T. 32. Deck AJ, True LD, Higano CS. Tricuspid valve metas-
Cardiac tumours: diagnosis and management. Lancet tasis from testicular carcinoma: a case report and
Oncol. 2005;6:219–28. review of the literature. Urology. 2000;56:330.
17. Vaitkus PT, Hermann HC, LeWinter MM. Treatment 33. Nand S, Messmore H. Hemostasis in malignancy. Am
of malignant pericardial effusion. JAMA. J Hematol. 1990;35:45–55.
1994;272:59–64. 34. Patterson WP, Ringenberg QS. The pathophysiology of
18. Cui Y, Urschel JD, Petrelli NJ. The effect of cardio- thrombosis in cancer. Semin Oncol. 1990;17:140–6.
pulmonary lymphatic obstruction in heart and lung 35. Bussani R, Silvestri F. Neoplastic thrombotic endo-
function. Thorac Cardiov Surg. 2001;49:35–40. carditis of the tricuspid valve in a patient with carci-
19. Patek PR. The morphology of the lymphatics of the noma of the thyroid. Report of a case. Pathol Res
mammalian heart. Am Heart J Anat. 1939;64: Pract. 1999;195:121–4.
203–49. 36. Dennis JL, Hvidsten TR, Wit EC, Komorowski J, Bell
20. Jellinek H, Gabor G, Solti F, Veress B. The problem AK, Downie I, Mooney J, Verbeke C, Bellamy C,
of the coronary changes due to disturbance of vascular Keith N, Oien KA. Markers of adenocarcinoma char-
wall permeability. Angiology. 1967;18:179–87. acteristic of the site of origin: development of a diag-
21. Riquet M, Grand B, Arame A, Pricopi CF, Foucault C, nostic algorithm. Clin Cancer Res. 2005;11:3766–72.
Dujon A, Le Pimpec Barthes F. Lung cancer invading 37. Tamura A, Matsubara O, Yoshimura NH, Kasuga T,
the pericardium: quantum of lymph nodes. Ann Akagawa A, Aoki N. Cardiac metastasis of lung can-
Thorac Surg. 2010;90:1773–7. cer. A study of metastatic pathways and clinical mani-
22. Yater WM. Tumors of the heart and pericardium: festations. Cancer. 1992;70:437–42.
pathology, symptomatology and report of 9 cases. 38. Loire R, Hellal H. Neoplastic pericarditis. Study by
Arch Int Med. 1931;48:627–66. thoracotomy and biopsy in 80 cases. Presse Med.
23. Scott RW, Garvin CF. Tumors of the heart and peri- 1993;22:244–8.
cardium. Am Heart J. 1939;17:431–6. 39. Brown RW, Campagna LB, Dunn K, Cagle PT.
24. Burnett RC, Shimkin MB. Secondary neoplasms of Immunohistochemical identification of tumor mark-
the heart. Arch Int Med. 1954;33:205–18. ers in metastatic adenocarcinoma. A diagnostic
25. Kayser K, Mattfeldt T, Mobius HJ. Herz metasta- adjunct in the determination of primary site. Am J
sierung beim primaren Bronchuskarzinom. Eine ret- Clin Pathol. 1997;107:12–9.
rospektive Autopsiestudie. Pathologe. 1986;7:143–8. 40. Wick MR, Lillemoe TJ, Copland GT, Swanson PE,
26. Willis RA. The spread of tumors in the human body. Manivel JC, Kiang DT. Gross cystic disease fluid pro-
London: J&A Churchill Ltd.; 1933. p. 259–68. tein-15 as a marker for breast cancer: immunohis-
27. Pratt CB, Dugger DL, Johnson WW, Ainger LE. tochemical analysis of 690 human neoplasms and
Metastatic involvement of the heart in childhood comparison with alpha-lactalbumin. Hum Pathol.
rhabdomyosarcoma. Cancer. 1973;31:1492–7. 1989;94:18–26.
Systemic Therapy, Radiotherapy,
and Cardiotoxicity 12
Chiara Lestuzzi, Gianmaria Miolo,
and Antonino De Paoli
high-dose therapy followed by autologous stem

Introduction cell transplantation may be considered. Several
standard high-dose regimens may be used:
Malignant cardiac tumors are usually sarcomas ifosphamide, carboplatin, etoposide (ICE), the
or Non-Hodgkin Lymphomas (NHL). The treat- same plus Taxol (TICE), etoposide, methyl
ment of NHL is based on chemotherapy (CT), prednisolone, high-dose cytarabine, cisplatin
and surgery is commonly used as a rescue therapy (ESHAP), dexamethasone, cisplatin, cytarabine
to treat severe hemodynamic impairment by a (DHAP), and dexamethasone, cisplatin, gemcit-
large mass. CT is often effective over a short abine (GDP) [1].
period of time in NHL (Figs. 12.1 and 12.2) and Although more frequent than primary lympho-
is the first choice treatment approach. The cyclo- mas, cardiac sarcomas are very rare and most of
phosphamide, doxorubicin, vincristine, and the published experiences consist of case reports
prednisone (CHOP) regimen has been the or small patient series. Also large institutions
mainstay of therapy for several decades, and the usually see roughly one patient/year or less
addition, in recent years, of Rituximab (R, a mono- (a few major referral centers may see up to 3–5
clonal antibody) has increased its efficacy with- patients/year), which makes it impossible to plan
out affecting toxicity; therefore, R-CHOP is the randomized studies to assess the best treatment
most commonly used first-line therapy even in approach [3–7]. Cardiac sarcomas are a small
elderly patients, usually as many as 6–8 cycles are subgroup of the more frequent (albeit rather rare)
given [1, 2]. In non-responders or relapsing patients, sarcomas of other sites (they represent roughly
1/100 of all sarcomas), and in most cases they
pertain to the soft tissue sarcomas (STS) group.
C. Lestuzzi, M.D. (*) Therefore, the basic therapeutic approach should
Department of Cardiology, Centro di Riferimento
be based on extrapolation of data from the most
Oncologico (CRO), IRCCS, National Cancer Institute,
Via F. Gallini 2, Aviano (PN) 33081, Italy frequent tumor sites, including STS of the
e-mail: clestuzzi@cro.it extremities and trunk [4, 7–9].
G. Miolo, M.D. Nevertheless, this approach may also be
Department of Medical Oncology, Centro di Riferimento affected by some of the peculiar characteristics of
Oncologico (CRO), IRCCS, National Cancer Institute, cardiac compared to noncardiac sarcomas.
Via F. Gallini 2, Aviano (PN) 33081, Italy
Cardiac sarcomas tend to be high grade, angio- or
A. De Paoli, M.D. leiomyosarcoma in histological subtype, and
Department of Radiation Oncology, Centro di
they usually have a propensity to occur at a
Riferimento Oncologico (CRO), IRCCS, National
Cancer Institute, Via F. Gallini 2, Aviano (PN) younger age [8–10]. In addition, cardiac sarcomas
33081, Italy are often metastatic at presentation and complete
166 C. Lestuzzi et al.
Fig. 12.1 Two-dimensional echocardiograms (apical four-chamber view) in a primary Non-Hodgkin lymphoma of the
left atrium. (a) At diagnosis; (b) after two courses of R-CHOP chemotherapy (see text for acronym)
resection with negative margins is achieved in non-metastatic tumors, and it seems to be effec-
20–45% of cases only [5, 7, 8, 11, 12]. For all tive in prolonging both time to relapse and sur-
these reasons, cardiac sarcomas are at higher risk vival in some selected studies (Table 12.1). The
of local or distant recurrence and they have a outcome data reported in different papers are
worse prognosis compared to STS of other more conflicting mainly for three reasons. There is a
frequent anatomical sites, including extremities, wide variety of tumor presentations (metastatic
superficial trunk, retroperitoneum, and head vs. non-metastatic, high-grade vs. low or interme-
and neck [9]. diate grade, right vs. left heart, surgery limited to
The standard treatment for localized STS the heart or including the lung), there is no stan-
consists of adequate surgery with “wide” resec- dardized surgical approach, and finally, in most
tion (i.e., with at least 1 cm of normal tissue studies, the multimodality therapy is limited to
around the tumor) followed by postoperative patients with incomplete resection or metastatic
radiation therapy (RT) in most cases. disease [11, 17–29]. Overall, when comparing
Preoperative RT may be an option for large studies with a multimodality approach, regard-
tumors or more critical tumor sites when ade- less of the surgical outcome, and historical studies
quate surgery with negative margins cannot be with CT used in some subgroups of patients only,
achieved [13, 14]. The role of adjuvant CT has there seems to be a favorable trend for the multi-
not been yet defined so far, but clinical practice modality approach (Fig. 12.3) [25, 29].
guidelines encompass it as an option in high-
risk patients [14, 15].
The particular location of cardiac sarcomas Systemic Therapy: Chemotherapy and
makes both surgery with curative intent and the Target Therapy (Table 12.2)
use of RT particularly challenging. While CT is
mandatory in metastatic and/or locally advanced, The “classic” and most commonly used CT regi-
unresectable disease, its use has been proposed mens for soft tissue sarcomas are based on a
for some critical locations, such as right heart/pul- combination of anthracyclines (ANTHRA) and
monary artery sarcomas, in an attempt to increase ifosfamide (IFO). However, more than 50 dis-
the number of resections with negative margins tinct histological subtypes of sarcoma have been
[11, 16]. Therefore, a multimodality approach, identified to date. Data are now available on the
including CT and/or RT before or after surgery, activity of some specific chemotherapeutic
has been used by several authors even for localized, agents for some selected histological subtypes.
12 Systemic Therapy, Radiotherapy, and Cardiotoxicity 167
Fig. 12.2 Magnetic resonance imaging in a case of Non- ual mass within the left atrium. (c) At last follow-up after
Hodgkin lymphoma. (a) At diagnosis the mass occupies 2 years there is complete remission (see text for acronym).
both atria, extending to pulmonary veins. (b) After three Courtesy of Dr. Sara Calamelli, General Hospital of
courses of R-CHOP chemotherapy there is a small resid- Mirano (VE), Italy
Angiogenesis, i.e., the formation of new blood

vessels, is integral to the growth and metastasis
of many malignancies, including STS, and it has
been suggested that the balance between factors
promoting the endothelial proliferation and vasal
formation and factors inhibiting these processes
are responsible for tumor progression [34]. Thus,
a therapy affecting the creation, growth, and
survival of new vessels (anti-angiogenic and/or
angiotoxic) has the rationale to be effective in
some tumors. The anti-angiogenic drugs showed
different mechanisms of action; some may inhibit
Fig. 12.3 Overall survival of patients treated with differ- selectively a single angiogenic protein, whereas
ent approaches: literature cases of non-resected cases others may inhibit two, three, or a wide range of
(Neragi), resected cases with or without chemotherapy angiogenic proteins involved in endothelial pro-
(Putnam), multimodality treatment of left heart tumors
with cardiac autotransplantation, and adjuvant chemo-
liferation and in microvascular sprouts. The drugs
therapy (Reardon). Courtesy of Prof. Michael J. Reardon, currently used or under evaluation in clinical trials
Methodist DeBakey Heart and Vascular Center, Houston, for STS (and considered as possible options for
TX, USA cardiac sarcomas) are Bevacizumab, Sunitinib,
Sorafenib, Dasatinib, Pazopanib, Thalidomide,
This should allow, in the near future, a histology- and Paclitaxel [34, 35]. The successful adminis-
driven CT approach for a better tailored treat- tration of anti-angiogenic factors observed in small
ment, including also cardiac sarcomas [30–33]. trials enrolling a variety of sarcomas may indicate
In addition, in the past 10 years, the increased a potential role in the treatment of highly vascular-
understanding of surface receptors expression nature cancers as heart angiosarcoma, which is the
and activity as well as of the molecular patho- most frequent cardiac sarcoma. Anti-angiogenic
genesis of various tumors has led to the develop- therapy has some peculiar aspects compared to
ment of the so-called target therapy. Target “classic” therapies. First, cytotoxic CT is often
therapy has significantly changed the treatment administered at the maximum tolerated dose with
of some of these tumors such as gastrointestinal a long off-therapy interval; anti-angiogenic ther-
stromal tumors (GIST), dermatofibrosarcoma pro- apy requires endothelial cell exposure to steady
tuberans, and aggressive fibromatosis. blood levels of the inhibitor and anti-angiogenic
Table 12.1 Mean and median survival of patients with primary malignant tumors of the heart; literature data
Author Years of Year of Institution No. of Treatment Median Mean Notes
(reference) recruitment publication patients survival survival
(months) (months)
Putnam 1964–1989 1991 MD Anderson 21 All treatments 11 15
[17] 5 Surgery 12 17 One alive
6 Surgery + CT 17 18 One alive
8 CT 10
only +/– debulking
Burke ND 1992 Armed Force 40 All treatments 6 11 30 complete,
[18] Institute of 10 incomplete
Pathology resection; 7
perioperative
deaths
12 Surgery 3 7
21 Surgery + CT/RT 12 19
Llombart- 1978–1995 1998 Gustave 19 All treatments 11
Cussac Roussy 6 Complete 23
[3] resection + CT
9 Incomplete 7
resection + CT
4 CT only 5
Centofanti 1980–1997 1999 University of 5 Wide resection 9 13
[20] Turin
Donsbeck 1968–1996 1999 Multicenter 24 All treatments 16
[19] 8 Complete NS
resection + CT/RT
15 Incomplete NS
resection/
biopsy + CT/RT
1 No therapy
Huo [22] 1990–2004 2006 12 All treatments 19 All pulmonary
artery
4 Surgery 9 2 alive, 1 lost
to follow-up
8 Surgery + CT/RT 21 4 alive, 2 lost
to follow-up
Mayer [8] 1993–2006 2007 South West 14 All treatments 15
German 6 Complete 15
Cancer Center resection ± CT
4 Palliative 15
resection + CT
4 CT only 15
Thomas- 1986–2005 2007 Marie 8 All treatments 26 17
de-Mont- Lannelongue, 2 Complete 34 34 Both interme-
preville Paris resection diate grade
[24] 4 Resection + CT 18 17 All high grade
2 Biopsy only ND
(continued)
Table 12.1 (continued)

Author Years of Year of Institution No. of Treatment Median Mean Notes
(reference) recruitment publication patients survival survival
(months) (months)
Simpson 1975–2007 2008 Mayo Clinic 34 All treatments 12
[5] 15 Complete 15
resection ± CT/RT
8 Incomplete 6
resection + CT
11 CT only or 5
nothing
Kim CH 1994–2006 2008 Cornell 24 All treatments 18
[6] University 5 Complete 10 1 alive
resection
19 Incomplete 25 4 alive
resection + CT
Kim HK 1999–2007 2008 Samsung 9 All treatments 19 19 All pulmonary
[25] Medical artery,
Center pneumonec-
tomy
4 Radical surgery 13 13 2 alive
5 Radical sur- 22 25 1 alive
gery + CT/RT
Zhang 1975–2006 2008 Multicenter 27 4 postoperative
[10] deaths, 10 lost
to follow-up
3 Surgery 54 54 2 alive, NED
3 Heart 27 39 All alive, NED
transplantation
7 Surgery + CT/RT 29 39 5 alive, 3 NED
Blackmon 1998–2008 2008 Methodist 18 All treatments 29 28 All left heart;
[29] DeBakey autotransplan-
Heart Center tation
2 Surgery 3 3
16 Surgery + CT/RT 29 28
Blackmon 1999–2006 2009 Methodist 8 Complete 24 All pulmonary
[26] DeBakey resection + CT/RT artery; 5 alive
Heart Center
Truong [7] 1990–2006 2009 British 16 All treatments 8 14
Columbia 10 Complete 25
Cancer resection ± CT/RT
Agency 6 Incomplete 6
resection/distant
disease + CT/RT
Hamidi [9] 1998–2005 2010 Multicenter 210 All treatments 6 Missing
subgroup data
125 With surgery 12
81 Without surgery 1
50 RT 11
159 No RT 4
CT chemotherapy, RT radiotherapy, ND not determined, NED no evidence of disease
Table 12.2 Systemic schedules most frequently administered in cardiac sarcomas

Epirubicin Ifosfamide
Dosage 60 mg/m2/die 1,8 g/m2/die
Frequency Days 1–2 Days 1–5 q3 weeks
Dosage 60 mg/m2/die 3 g/m2/die
Doxorubicin Ifosfamide
Dosage 50 mg/m2 5 g/m2
Frequency Day 1 Day 1 q3 weeks
Dosage 25 mg/m2/die continuous infusion 2 g/m2/die
Dosage 30 mg/m2 3 g/m2
Frequency Day 1 Days 1–3 q3 weeks
Dose intensive chemotherapy
Dosage 75 mg/m2 72 h infusion 2 g/m2/day
Frequency Days 1–3 Day 1–5 q3 weeks
Dosage 90 mg/m2 72 h infusion 2.5 g/m2/day
Pegylated liposomal doxorubicin
Dosage 20 mg/m2
Frequency Days 1, 15 q4 weeks
Dosage 30 mg/m2
Frequency Day 1 q3 weeks
Paclitaxel
Dosage 80 mg/m2
Frequency Days 1, 8, 15 q4 weeks
Gemcitabine
Dosage 1,000 mg/m2/die
Frequency Days 1, 8, 15 q4 weeks
Gemcitabine Docetaxel
Dosage 900 mg/m2 100 mg/m2
Frequency Days 1, 8 Day 8 q3 weeks
Dosage 675 mg/m2 75 mg/m2
Frequency Days 1, 8 Day 8 q3 weeks
Experimental drugs
Sorafenib
Dosage 400 mg oral twice per day
Frequency Continuously
Imatinib
Dosage 600 mg/die per os
Frequency Continuously
Bevacizumab
Dosage 15 mg/kg
Frequency Day 1 q3 weeks
agents with a short half-life might need to be blood levels that are too low or too high may be
dosed daily and without any breaks [35]. ineffective in the inhibition of angiogenesis; there-
Secondly, anti-angiogenic agents tend to have a fore, more is not necessarily better when it comes
biphasic, U-shaped dose–efficacy curve where to anti-angiogenesis [33].
Anthracyclines and Ifosfamide equivalent activity in comparison to DOX

[47–49]. Furthermore, pegylated liposomal
With the commonly employed first-line CT of STS, ANTHRA have also produced satisfactory
an objective response rate of 45%, including 10% results in the treatment of angiosarcoma and
of complete response and a median survival of 15 lymphangiosarcoma [50, 51].
months, has been obtained [36, 37]. Accordingly,
the standard systemic approach to patients with
advanced/unresectable sarcomas of the heart and Taxanes
great vessels or to those who have progressed from
earlier stages remains to be the chemotherapeutic Paclitaxel and Docetaxel are natural alkaloids
ANTHRA-based regimen [33, 38]. active for several tumor types from ovarian to
Doxorubicin (DOX)-based CTs (DOX 50 mg/ breast and lung cancers. They act as cytotoxic
m2/die on day 1 and IFO g/m2/die on day 1 or drugs by inhibiting microtubular assembly.
DOX 25 mg/m2/die on days 1, 2, and 3 and IFO Paclitaxel has also anti-angiogenesis effects
2 g/m2/die per day on days 1–5) or epidoxorubi- by inhibiting endothelial motility and prolif-
cin (epiDOX)-based regimens (epiDOX 60 mg/ eration as well as invasiveness [34, 52]. Many
m2/die on days 1 and 2 and IFO 3 g/m2/die on different anticancer drug combinations, includ-
days 1–3) are now the conventional first-line ing gemcitabine and docetaxel, have been
treatments [39–41]. A Cochrane review showed demonstrated to have greater activity than
that combination regimens, compared with sin- gemcitabine alone [30, 53, 54]. Gemcitabine is
gle-agent DOX, achieved only marginal given on days 1 and 8 at 900 mg/m2 over 90
increases in response rates at the expense of min and docetaxel at 100 mg/m2 over 60 min.
increased toxic effects and with no improve- Typically the most sensitive histological type
ments in overall survival [42]. Moreover, it to the combination of gemcitabine and doc-
should be emphasized that most of the CT agents etaxel in the salvage setting is fibrohistiocytic
used in cancer management have demonstrated sarcoma (or malignant fibrous histiocytoma) [33].
a dose–response relationship. For DOX, in a Weekly paclitaxel has been shown to carry out
randomized dose–response study the response an important role in the treatment of patients
rate was twice as high at the dose of 75 mg/m2 with heart angiosarcoma [55]. In a retrospec-
as compared with 45 mg/m2 [43]. Since response tive study enrolling 32 patients with pretreated
rate increases at higher doses, the increase of angiosarcomas, 3 out of 5 patients with heart
dose intensity may be an important strategy to angiosarcoma showed stable disease or
favor the response rate and reduce the relapse response to paclitaxel [56]. Not surprisingly,
rate. For IFO, the data are weaker, even if an the weekly paclitaxel schedule (80 mg/m2/die) is
higher response rate at higher doses has been linked to diverse activities, from anti-angiogenesis
reported [44]. In young patients with optimal to pro-apoptotic effects. In a series of in vitro
performance status may be more useful to and in vivo experiments it has been observed
administer high doses of DOX (90 mg/m2) and that low-dose schedules of paclitaxel were
IFO (10 g/m2) preceded by granulocytic growth significantly capable of causing an inhibition
factors and cardioprotective agents [45]. The in endothelial cell proliferation, motility, and
pegylated liposomal form of DOX accumulates invasiveness [52, 57, 58]. There is abundant
preferentially in tissues with increased micro- evidence, therefore, that the weekly paclitaxel
vascular permeability, such as the case of most possesses different mechanisms of action com-
tumors with active neoangiogenesis [46]. The pared with triweekly paclitaxel. However, the
first clinical studies with pegylated liposomal activity of taxanes is higher in scalp angiosar-
DOX in the treatment of extracardiac sarcomas coma than in primary angiosarcomas of other
have shown variable results in response rates sites and ineffective for other histological
with improved toxicity pro fi le and at least subtypes of STS [59].
no prospective randomized trials have been con-

Target Therapy (Bevacizumab, Tyrosine ducted. On the other hand, it is also possible that
Kinase Inhibitors) sunitinib efficacy may be underestimated when
local evaluation of anatomic response is per-
Bevacizumab (Avastin®) is a humanized mono- formed using changes in tumor size according to
clonal antibody which neutralizes all isoforms of RECIST criteria [60]. Sorafenib inhibits the RTKs
vascular endothelial growth factor (VEGF) and it VEGFR1-3, FLT-3, c-KIT, PDGFR-b, and p38
is approved for the treatment of metastatic col- tyrosine kinases, which block the VEGF- and
orectal cancer, metastatic non-squamous non- PDGF-dependent angiogenesis. In a phase II trial
small-cell lung cancer, metastatic breast cancer, that evaluated the activity of sorafenib in patients
recurrent glioblastoma multiforme, and metastatic with metastatic sarcoma, five of 37 patients with
renal cell carcinoma. Though the inhibition of angiosarcoma had a partial response (response
tumor angiogenesis was originally thought to rate 14%); in this subgroup median progression-
simply aggravate hypoxia, VEGF inhibition has free survival was 3.8 months whereas median
also been shown to induce so-called vascular nor- overall survival was 14.9 months. Therefore this
malization, a restoration of normal structure, study provides important information on the rela-
function, and flow to the disorganized vessels tive activity and safety profile of this drug used in
characteristic of malignant tumors, allowing an this setting of patients [61], demonstrating that
improvement of the delivery of oxygen, nutrients, sorafenib has activity against angiosarcoma and
and cytotoxic CT to the tumor. Bevacizumab has minimal activity against other sarcomas. In a
been shown to have a limited antitumoral activity nother study imatinib (600 mg/die) used in
as monotherapy; therefore it has been combined patients with advanced or metastatic angiosarcoma
with cytotoxic or cytokine therapy. Data about the attained a response rate about 12% whereas the
use of bevacizumab combined with DOX in STS non-progression rate was only 20% at 3 months
are limited, and this approach deserves further [62]. Other angiogenic regulators as endostatin
investigation [34]. Some patients with cancer are and caplostatin could carry out, in the future, an
or become refractory to VEGF-inhibitor treat- important role in the treatment of heart sarcomas
ment; a mechanism of acquired resistance is the [33, 63]. In conclusion, at the present, the recom-
increased reliance on alternative pro-angiogenetic mended first-line regimen in cardiac sarcomas
factors that do not use the VEGF pathway. VEGF remains to be the ANTHRA/IFO; taxanes and/or
blockade inhibits sprouting angiogenesis, but may gemcitabine have demonstrated a good activity,
not be as efficient in suppressing other modes of are used in the metastatic setting, and may be con-
tumor vascularization. Therefore, inhibitors of sidered as first line for angiosarcomas (Figs. 12.4
several pathways implicated in tumor growth and 12.5). New targeted drugs are under evalua-
angiogenesis and metastasis may offer advantages tion and may be used in relapsing or refractory
over inhibition of a single pathway. Sunitinib tumors. An interesting new field of research in tar-
inhibits the tyrosine kinase receptors (RTKs) get therapy is focused on cancer stem cell charac-
VEGFR1-3, platelet-derived growth factor recep- terization and on the proteomics approach, but it
tor alpha (PDGFR-a), platelet-derived growth is still far from clinical application [64].
factor receptor beta (PDGFR-b), FMS-like
tyrosine kinase 3 (FLT-3), c-KIT receptor, RET,
and colony-stimulating factor receptor type 1, Radiation Therapy
some of which have been implicated in tumor
growth angiogenesis and metastasis. There is no Historically, RT has played a minor role in the
clear evidence on utility and efficacy of this agent management of patients with cardiac sarcomas
in the treatment of heart sarcomas since the avail- primarily because of the low tolerance of the
able data come from anecdotal case reports and whole heart to RT and the challenge associated
Fig. 12.4 Transthoracic two-dimensional echocardiogram orifice. (b) After three courses of Taxol chemotherapy the
(apical four-chamber view) in a case of angiosarcoma. (a) mass is reduced in size. (c) After IMRT-Tomotherapy the
At diagnosis a large mass infiltrates the right atrial and mass is further reduced in size. At this time the patient
right ventricular walls and prolapses through the tricuspid underwent complete resection (see text for acronym)
Fig. 12.5 Transesophageal echocardiogram in a case of IFO plus liposomal DOX the mass is markedly reduced in
right atrium angiosarcoma. Top horizontal plane, bottom size. (c) After tomotherapy the mass is further reduced in
sagittal plane. (a) At diagnosis a mass infiltrates exten- size; the interatrial septum is no more infiltrated. The
sively the right atrial walls, roof, and interatrial septum patient underwent then successful removal of the whole
and is judged unresectable. (b) After chemotherapy with residual mass (see text for acronyms)
with delivering highly conformal RT to the car- Advancements that allow the safe delivery of
diac tumor, or tumor bed after resection, while higher dose RT to cardiac tumors include
sparing the non-tumor-bearing surrounding heart advanced imaging to improve tumor definition,
tissue. Although a clear correlation of dose-vol- 3-dimensional radiation (3D-CRT) planning
ume predictors for acute and late radiation- techniques to deliver high dose which conform
induced heart disease (RIHD) has not yet been tightly to the tumor, image-guided RT (IGRT) to
defined, a risk >5% of RIHD after whole-heart localize the tumor at the time of treatment, organ
RT of 30–35 Gy given over 4 weeks is reported motion evaluation for appropriated planned
[65]. Such dose of 30–35 Gy is lower than the target-volume definition, and improved knowl-
dose required to eradicate the tumor. edge of the partial volume tolerance of the heart
Fig. 12.6 Radiotherapy plan of 3D conformal radiother- 45 Gy in 25 fractions to include all the left atrium and the
apy for a left atrial sarcoma infiltrating the interatrial sep- involved structures with organ motion margins (sparing
tum, atrial roof, lateral and posterior free wall, and uninvolved heart), and higher dose up to 59.4 Gy limited
posterior mitral annulus. (a) 2D plan, aiming to give to the residual tumor mass. (b) 3D reconstruction
to radiation [66–69]. With such technological An example of a IMRT-IGRT tomotherapy plan

advances, it has been possible to deliver a higher for a patient with right atrial sarcoma is reported
dose to cardiac tumors than was previously pos- in Fig. 12.7. With 3D-CRT or, more recently, by
sible with a low risk of complications. An exam- IMRT-IGRT Tomotherapy, it is possible to give
ple of a 3D-CRT plan for a patient with left atrial RT dose as high as 45–59.4 Gy/25–33 fractions,
sarcoma is reported in Fig. 12.6. over 5–6 weeks in patients with unresectable or
Intensity-modulated RT (IMRT) is another partially resected cardiac sarcomas, as recently
technological advancement that facilitates the reported by our group [70]. Echocardiography
delivery of highly conformal RT. With IMRT, examination was used in the treatment planning
radiation is delivered with multiple small fields for organ motion evaluation and margin target-
(“segments”) within each beam, producing a volume definition. Individualized dose con-
modulated fluence pattern for each beam angle. straints to left and right ventricle were included
Computer-aided, automated optimization of seg- (Fig. 12.7). Two patients with unresectable tumor
ments weights (or “inverse planning”) is con- at presentation had major response to CT-RT and
ducted to obtain to the best target coverage and underwent a successful complete surgical resec-
sparing of dose to normal tissues. Clinical expe- tion. At a median follow-up of 22 months (range
rience with IMRT for the treatment of cardiac 3–84 months), nine patients were alive and six of
sarcomas is limited. However, planning study them free of disease. In our experience, RT for
comparison between IMRT and 3D-CRT sug- cardiac sarcomas demonstrated a feasible
gests that IMRT may have a potential benefit for approach, also when combined with CT and surgery.
some patients with cardiac sarcomas [70]. The These results confirm previous published experi-
Tomotherapy system, a technological facility, ences in selected series of patients (Table 12.1).
is a dedicated IMRT linear accelerator that Technological advances in RT planning and
integrates IMRT by means of dynamic rota- delivery and further insight into RT cardiac tol-
tional therapy (helical tomotherapy) and IGRT erance appeared crucial in minimizing the risk of
by means of megavolt computerized tomogra- RIHD. Further experience is needed to confirm
phy (MVCT) allowing an optimal, evaluated, these encouraging results and to attempt a multi-
and optimized target-volume dose distribution, disciplinary approach with curative intent also in
and a daily accurate patient positioning [69]. these unfavorable sarcomas.
Fig. 12.7 Radiotherapy plan of preoperative IMRT-IGRT dose escalation up to 54 Gy in 25 fractions limited to
tomotherapy for a tumor involving the right atrium (roof, the tumor (equivalent to 60 Gy in 2 Gy fraction).
lateral free wall, tricuspid annulus). This patient had unre- Uninvolved heart was optimally spared (see text for
sectable angiosarcoma and was treated with 45 Gy with acronyms). (a) Radiation planning before treatment. (b)
a highly conformal plan with IMRT to include all the Planning and treatment computed tomography fusion before
atrium with organ motion margins and a simultaneous each radiation fraction
expression. The final myocyte damage is then

Cardiotoxicity both iron-dependent and iron-independent [71–
73]. Ultrastructural early alteration in damaged
Anthracyclines myocytes consists of distension of sarcoplasmic
reticulum to form sarcoplasmic vacuoles, fol-
Cardiotoxicity has been known as one of the lowed by myofibrillar lysis and focal prolifera-
most important and limiting side effects of DOX tion of sarcoplasmic reticulum, disruption of
and other ANTHRA for decades. The exact myofibrils, atrophy, and necrosis; interstitial
pathophysiology has been debated for a long edema and eventually fibrosis are observed in
time, and is probably due to a complex interac- more severe forms; myocardial damage has been
tion of several factors: iron-mediated formation reported to be most severe in the left ventricle
of Reactive Oxygen Species (ROS), membrane (LV) and in the ventricular septum, intermediate
lipid peroxidation, inhibition of nucleic acids in the right ventricle and the left atrium, and least
and protein synthesis, altered calcium homeosta- in the right atrium [74]. Each single dose of DOX
sis, mitochondrial disruption, apoptotic response, causes an irreversible cardiac damage; for this
formation of toxic alcoholic metabolites (DOXOL), reason the cardiotoxicity is cumulative, even for
and alterations of the cardiac-specific gene CT given many years apart. The final effect is
diastolic and systolic left ventricular dysfunction (c) The use of EpiDOX that is roughly 30% less
and, in the most advanced stages, congestive cardiotoxic compared to DOX, and less poten-
heart failure (CHF). In an attempt to reduce car- tiated by the concomitant use of taxanes.
diotoxicity, several DOX analogues have been (d) The use of liposomal formulations that limit
developed: EpiDOX, Idarubicin (orally avail- the cardiac uptake of the drug leaving unal-
able), Mitoxantrone, and—more recently—lipo- tered the tumor delivery.
somal DOX formulations. The incidence of both CHF due to ANTHRA toxicity was consid-
asymptomatic and symptomatic cardiac dysfunc- ered refractory to medical therapy for years; at
tion depends mostly on the cumulative dose: present, the use of conventional drugs as ACE-
CHF is rather low (around 5%) up to a total dose inhibitors and beta-blockers has been proven
of 400 mg/sm of DOX and then increases expo- effective both in treating overt cardiotoxicity and
nentially (raising to 26% at a dose of 550 mg/m2 in preventing the progression of LV dysfunction
and to 40% above 700 mg/m2), and asymptom- in subjects at high risk with preclinical signs of
atic LV dysfunction is observed in 9% at a cumu- cardiac damage [82–85]. So, besides the above-
lative dosage of 250 mg/sm, and 65% above mentioned strategies to prevent cardiotoxicity, a
550 mg/m2 [75]. Several risk factors have been strict monitoring during the treatment is recom-
indentified for ANTHRA cardiotoxicity: age mended; at the first signs of LV dysfunction
<18 and >60 years, preexisting cardiac disease therapy with ACE-inhibitors should be started.
(ischemic, hypertensive) and/or LV dysfunction,
concomitant RT involving the heart, and high
concentration of the single dose [75, 76]. Of par- Ifosfamide
ticular concern is the delayed onset of cardiotox-
icity in long-term cancer survivors; recent studies The main reported toxicities of IFO are nephro-
have demonstrated that the alcoholic metabolites toxicity and neurotoxicity. From the cardiac point
(like DOXOL and EpiDOXOL) are retained of view it has been usually considered safe, but
within the myocardial cell much longer than the cardiac toxicity in high-dose (>10 g/m2) treated
parent drug, and may represent a lifelong toxic patients has been reported, and is significant (>10%)
reservoir inducing a heart frailty when exposed when using >15 g/m2 [83, 86–88]. Possibly, there
to other stressors and that these toxic metabolites is a link between nephrotoxicity and cardiotoxic-
increase when DOX is administered together ity: the LV dysfunction follows usually an
with taxanes [71, 77]. A number of strategies increase in blood creatinine, and—according to a
have been explored to prevent or reduce recent experimental study—IFO-induced Fanconi
ANTHRA cardiotoxicity: changes in infusion syndrome may cause a carnitine deficiency dan-
schedules; association of antioxidants (vitamin gerous for the heart [87, 89]. Since IFO is usually
E, selenium, and so on), calcium-channel block- given together with ANTHRA, a strict follow-up
ers, iron-chelators (as Dexrazoxane), angio- using echocardiography and myocardial damage
tensin-converting enzyme (ACE) inhibitors, and biomarkers (in order to early diagnosing and
beta-blockers; and cardiac monitoring with serial treating LV dysfunction) is recommended [83].
LV function assessment or with biomarkers as
troponins. The most effective ways to prevent
cardiotoxicity are [73, 78–81]: Taxanes
(a) The concomitant use of dexrazoxane, an iron-
chelating agent, that has been proven to Taxane cardiotoxicity is mainly evident as
significantly reduce cardiac dysfunction with- self-limiting supraventricular arrhythmias (atrial
out affecting the antineoplastic effect of DOX. fibrillation, sinus bradycardia), but they may also
(b) The use of prolonged infusions (>6 h; prefer- increase DOX (much less EpiDOX) toxicity, as
ably 48–72 h continuous infusions) rather than above mentioned, altering ANHTRA pharma-
bolus administration. cokinetics and possibly promoting the formation
of toxic metabolites [71, 72, 87]. To prevent this effects due to the VEGF block, in fact, there are a
problem, the two drugs should be administered number of off-target effects common to the whole
apart, and DOX before taxanes. Cases of allergic class of TKI: most important are myocardial
myocarditis have also been reported, mostly with damage and prolongation of QT interval at ECG
paclitaxel; some authors argued that they could (with the risk of life-threatening ventricular
be due not to the drug itself but to its solvent, the arrhythmias). Different molecules have different
Cremophor EL [72, 87]. Moreover, anaphylactic cardiotoxicity, and besides the dozens of TKI
reactions (ARs) have been frequently described already in use, there are hundreds still under eval-
with taxanes, with a mortality reported more uation: the topic of TKI cardiotoxicity is an
often with docetaxel than paclitaxel; prophylactic everyday changing field, and the mechanisms are
pre-medications did not significantly impact mor- still to be defined [92, 94]. In fact, the role in car-
tality from ARs with docetaxel, but was associ- diac physiopathology of the 90 human tyrosine
ated with significantly lower mortality from ARs kinases (and, then, the effect of their block) is
with paclitaxel [90]. largely unknown; some of them protect the myo-
cardial cell from ischemic or oxidative stress, are
involved in the reparative process after myocar-
Vascular Endothelial Growth Factor dial ischemia, or have generally an antiapoptotic
Blocking Agents and Tyrosine Kinase action. According to the most recent studies,
Inhibitors TKI-induced LV dysfunction is due to a direct
cytotoxic effect, with mechanisms different from
Two types of side effects have to be considered: ANTHRA cardiotoxicity, cannot be prevented by
on-target (due to the same mechanisms acting as dexrazoxane, and is not always reversible upon
antitumoral; these effects may be also a biologi- withdrawal of the drug or even with commonly
cal marker of antineoplastic efficacy) and off- used cardiac therapy with ACE-inhibitors and
target. The VEGF block (by the monoclonal beta-blockers; the risk is inversely proportional
antibody Bevacizumab and the tyrosine kinase to the selectivity of TKI [94–96]. Since LV dys-
inhibitors (TKI) Sunitinib and Sorafenib) causes function seems to be more frequent in patients
hypertension (mainly by reducing the nitric oxide with uncontrolled hypertension, and according to
release by the endothelial cells, by interfering the experimental data, probably the cardiotoxic
with renal physiology, and by increasing the vas- effect of anti-VEGF drugs may be due to a com-
cular resistance), thromboembolism, and hemor- bination of hypertensive stimulus and of inhibi-
rhages [90–92]. Moreover, the activation of tion of the homeostatic mechanisms protecting
VEGF is crucial in wound repair, in maintaining the myocardium from the pressure overload stress
capillary density in the hypertrophied heart, and (on-target effect); as regards Sunitinib and other
for the neoangiogenesis in ischemic and diabetic multitarget TKI, there might be additionally a
heart disease; its block may then have deleterious direct cytotoxic effect (off-target effect). For
effects in patients with preexisting cardiac diseases these reasons, the only strategies to prevent LV
or undergoing cardiotoxic CT. There are some dysfunction are presently an accurate manage-
differences among the pharmacokinetics of these ment of hypertension and a regular echocardio-
three drugs: Sunitinib and Sorafenib have an half- graphic follow-up.
life of hours, while Bevacizumab half-life varies
from 10 to 50 days (mean 20) in different patients:
during prolonged treatments, then, Bevacizumab Radiotherapy
may cause a progressively worsening hyperten-
sion. After introducing in the market Sunitinib Data about radiation heart disease are derived by
and Sorafenib, an unexpectedly high rate of car- studies in two kinds of human populations (the
diovascular side effects, including a direct myo- atomic bomb survivors and the long-term survivors
cardial damage, has been noticed. Besides the of tumors—mostly Hodgkin’s disease and left
Table 12.3 Echocardiographic ejection fraction (EF) before chemotherapy (CT), after CT and before radiotherapy
(RT), and at last follow-up after RT
Sex, age (type of CT/RT INTENT Site EF before EF before EF after Follow-up State at follow-up
RT) (surgical status) CT (%) RT (%) RT (%) (months)
m 57 (3D-CRT) Curative LA 58 65 58 101 Alive NED
(unresectable)
m 61 (IMRT)* Adjuvant (R2 PA 64 68 20 Dead of 2nd
resection) neoplasm
m 25 (3D-CRT) Curative RA, SVC 60 62 49 36 Dead of local
(unresectable) progression
f 58 (IMRT) Adjuvant (R1 LA, LV 64 62 58 36 Alive with
resection) metastases
m 44 (3D-RT) Curative RA, RV 69 65 66 12 Dead of metastases
(unresectable)
f 69 (IMRT) Curative (incom- LA 72 72 70 15 Dead of metastases
plete resection
m 39 (Tomo) Adjuvant (R2 RA, IAS 68 58 63 20 Dead of metastases
resection)
m 72 (Tomo)§ Neoadjuvant # RA, RV 70 69 59 16 Dead of local relapse
f 57 (Tomo) Adjuvant (R2 RA, LA 72 72 68 21 Alive with local
resection) disease
m 39 (Tomo) Palliative after Pericardium 70 53 63 13 after Dead of local
local relapse relapse, 34 progression
overall
m 44 (Tomo) Neoadjuvant # RA, IAS 62 64 65 16 Dead of metastases
Patient signed with: asterisk symbol did not receive any CT, signed with section symbol taxanes only, and signed with
hash symbol had radical surgery after neoadjuvant CT/RT
3D-CRT 3-dimensional conformational RT, IMRT intensity-modulated RT, Tomo tomotherapy, f female, m male, nd not deter-
mined, IAS interatrial septum, LA left atrium, LV left ventricle, PA pulmonary artery, RA right atrium, RV right ventricle, NED no
evidence of disease
breast cancer—undergone therapeutic irradiation), (with classical signs and symptoms of pericardial
and by animal experiments. Ionizing radiation may rubs and pain) that can be cured with Nonsteroidal
cause acute symptomatic effects, and chronic or Anti-inflammatory Drugs. In both cases, pericar-
delayed effects. Coronary artery disease, valvular dial effusion is usually mild to moderate, and in
heart disease, and constrictive pericarditis are the 80% of cases there are no reliquates, while in 20%
typical chronic side effects affecting long-term sur- the disease evolves toward a constrictive pericardi-
vivors: they become clinically evident usually 10 tis [97]. The microvessel damage is followed by a
years after treatment, with increasing incidence at persistent decrease in capillary density and eventu-
longer follow-up [67]. Since the 5-years survival of ally leads to chronic myocardial ischemia and
patients with malignant cardiac tumors is still low, degeneration; an impairment in myocardial perfu-
the main problem, in these particular patients, is the sion may be observed in the first months after RT,
acute or medium-term cardiac toxicity. The first even if the increased risk of clinically evident
acute effect of irradiation is a pro-inflammatory RT-linked ischemic heart disease becomes statisti-
effect, with endothelial damage of medium-large cally significant only after 10 years [68, 97–100].
vessels and microvessels, pericarditis, and myo- In our experience, using modern radiation tech-
carditis; mast cells seem to have a protective effect niques, we did not observe any clinically relevant
[66–68]. Pericardium is the most frequently myocardial dysfunction on the short-medium term
affected site: acute pericarditis is associated with of observation in 11 patients with cardiac tumors
edematous swelling of the pericardial layers: it may treated with RT with or without previous CT,
present in a painless effusive form with spontane- including three long-term >30 months survivors
ous recovery, or as an acute fibrinous pericarditis [70] (Table 12.3).
JT. Primary malignant sarcomas of the heart and

Conclusions great vessels in adult patients. A single-center experi-
ence. Oncologist. 2007;12:1134–42.
9. Hamidi M, Moody JS, Weigel TL, Kozak KR.
Malignant heart tumors are usually aggressive and Primary cardiac sarcoma. Ann Thorac Surg.
have a dismal prognosis. The mainstay of therapy 2010;90:176–81.
for sarcomas is radical surgery. Multimodality 10. Zhang PJ, Brooks JS, Goldblum JR, Yoder B,
Seethala R, Pawel B, Gorman JH, Gorman RC,
treatment including systemic therapy and/or RT Huang JH, Acker M, Narula N. Primary cardiac sar-
seems to prolong the time to relapse and overall comas: a clinicopathologic analysis of a series with
survival. Most of the treatments have a consider- follow-up information in 17 patients and emphasis on
able risk of cardiac toxicity, but this risk should be long-term survival. Hum Pathol. 2008;39:1385–95.
11. Vaporciyan A, Reardon MJ. Right heart sarcomas.
balanced against the risk of tumor progression. Methodist Debakey Cardiovasc J. 2010;6:44–8.
Since the survival is usually limited to few years, 12. Reardon MJ. Malignant tumor overview. Methodist
the main concern is to prevent short- and medium- Debakey Cardiovasc J. 2010;6:35–7.
term toxicity. CT adverse effects may be prevented 13. NCCN Practice Guidelines in Oncology (NCCN
GuidelinesTM). Soft tissue sarcomas. Version 1.
with careful dosage of drugs, cardioprotective 2011. http://www.NCCN.org.
agents, and strict monitoring of cardiac function. 14. Casali PG, Blay JY, ESMO/CONTICANET/
Short- and medium-term cardiac toxicity of RT EUROBONET Consensus Panel of Experts. Soft tis-
may be limited using modern radiation techniques. sue sarcomas: ESMO Clinical Practice Guidelines
for diagnosis, treatment and follow-up. Ann Oncol.
A number of new targeted therapies are under 2010;21 Suppl 5:v198–203 (Erratum in: Ann Oncol.
evaluation and will hopefully improve the outcome 2010;21:1736).
of this severe pathology. 15. Pervaiz N, Colterjohn N, Farrokhyar F, Tozer R,
Figueredo A, Ghert M. A systematic meta-analysis
of randomized controlled trials for adjuvant chemo-
therapy for localized soft tissue sarcoma. Cancer.
References 2008;113:573–81.
16. Blackmon SH, Reardon MJ. Pulmonary artery
1. Flowers CR, Sinha R, Vose JM. Improving outcomes sarcoma. Methodist Debakey Cardiovasc J.
for patients with diffuse large B-cell lymphoma. CA 2010;6:38–43.
Cancer J Clin. 2010;60:393–408. 17. Putnam JB, Sweeney MS, Colon R, Lanza LA,
2. Tilly H, Dreyling M, ESMO Guidelines Working Frazier OH, Cooley DA. Primary cardiac sarcomas.
Group. Diffuse large B-cell non-Hodgkin’s lym- Ann Thorac Surg. 1991;51:906–10.
phoma: ESMO clinical practice guidelines for diag- 18. Burke AP, Cowan D, Virmani R. Primary sarcomas
nosis, treatment and follow-up. Ann Oncol. 2010;21 of the heart. Cancer. 1992;69:387–95.
Suppl 5:v172–4. 19. Donsbeck A-V, Ranchere D, Coindre J-M, Le Gall F,
3. Llombart-Cussac A, Pivot X, Contesso G, Rhor- Cordier J-F, Loire R. Primary cardiac sarcomas: an
Alvarado A, Delord JP, Spielmann M, Tűrsz T, Le Cesne immunohistochemical and grading study with
A. Adjuvant chemotherapy for primary cardiac sarco- long-term follow-up of 24 cases. Histopathology.
mas: the IGR experience. Br J Cancer. 1998;78:1624–8. 1999;34:295–304.
4. Debourdeau P, Gligorov J, Teixeira L, Aletti M, 20. Centofanti P, Di Rosa E, Deorsola L, Dato GM,
Zammit C. Tumeurs cardiaques malignes. Bull Patanè F, La Torre M, Barbato L, Verzini A, Fortunato
Cancer. 2004;91:S136–46. G, di Summa M. Primary cardiac tumors: early and
5. Simpson L, Kumar SK, Okuno SH, Schaff HV, late results of surgical treatment in 91 patients. Ann
Porrata LF, Buckner JC, Moynihan TJ. Malignant Thorac Surg. 1999;68:1236–41.
primary cardiac tumors. Review of a single institu- 21. Bakaeen FG, Reardon MJ, Coselli JS, Miller CC,
tion experience. Cancer. 2008;112:2440–6. Howell JF, Lawrie GM, Espada R, Ramchandani
6. Kim CH, Dancer JY, Coffey D, Zhai QJ, Reardon M, MK, Noon GP, Weilbaecher DG, DeBakey ME.
Ayala AG, Ro JY. Clinicopathologic study of 24 patients Surgical outcome in 85 patients with primary cardiac
with primary cardiac sarcomas: a 10-year single institu- tumors. Am J Surg. 2003;186:641–7.
tion experience. Hum Pathol. 2008;39:933–8. 22. Huo L, Moran CA, Fuller GN, Gladish G, Suster S.
7. Truong PT, Jones SO, Martens B, Alexander C, Pulmonary artery sarcoma. Am J Clin Pathol.
Paquette M, Joe H, Hart J, Allan SJ. Treatment and 2006;125:419–24.
outcomes in adult patients with primary cardiac sar- 23. Neragi-Miandoab S, Kim J, Vlahakes GJ. Malignant
coma: the British Columbia Cancer Agency experi- tumors of the heart: a review of tumor type, diagno-
ence. Ann Surg Oncol. 2009;16:3358–65. sis and therapy. Clin Oncol. 2007;19:748–56.
8. Mayer F, Aebert H, Rudert M, Königsrainer A, 24. Thomas-de-Montpréville V, Nottin R, Dulmet E,
Horger M, Kanz L, Bamberg M, Ziemer G, Hartmann Serraf A. Heart tumors in children and adults:
clinicopathological study of 59 patients from a surgi- 38. Grimer R, Judson I, Peake D, Seddon B. Guidelines
cal center. Cardiovasc Pathol. 2007;16:22–8. for the management of soft tissue sarcomas. Sarcoma.
25. Kim HK, Choi YS, Kim K, Shim YM, Sung K, Lee 2010;2010:506182.
YT, Park PW, Kim J. Surgical treatment for pulmo- 39. Casali P, Pastorino U, Azzarelli A, Bertulli R,
nary artery sarcoma. Eur J Cardio-Thoracic Surg. Zucchinelli P, Devizzi L, Santoro A. Perspectives on
2008;33:712–6. anthracyclines plus ifosfamide in advanced soft tis-
26. Blackmon SH, Rice DC, Correa AM, Mehran R, sue sarcoma. Cancer Chemother Pharmacol. 1993;31
Putnam JB, Smythe WR, Walkes JC, Walsh GL, Suppl 2:S228–32.
Moran C, Singh H, Vaporciyan AA, Reardon M. 40. Sarcoma Meta-analysis Collaboration. Adjuvant
Management of primary pulmonary artery sarcomas. chemotherapy for localised resectable soft-tissue
Ann Thorac Surg. 2009;87:977–84. sarcoma of adults: metaanalysis of individual data.
27. Bakaeen FG, Jaroszewski DE, Rice DC, Walsh GL, Lancet. 1997;350:1647–54.
Vaporciyan AA, Swisher SS, Benjamin R, Blackmon 41. Frustaci S, Gherlinzoni F, De Paoli A, Bonetti M,
S, Reardon MJ. Outcomes after surgical resection of Azzarelli A, Comandone A, Olmi P, Buonadonna A,
cardiac sarcoma in the multimodality treatment era. Pignatti G, Barbieri E, Apice G, Zmerly H, Serraino
J Thorac Cardiovasc Surg. 2009;137:1454–60. D, Picci P. Adjuvant chemotherapy for adult soft tis-
28. Orlandi A, Ferlosio A, Roselli M, Chiariello L, sue sarcomas of the extremities and girdles: results
Spagnoli LG. Cardiac sarcomas. An update. J Thorac of the Italian randomized cooperative trial. J Clin
Oncol. 2010;5:1483–9. Oncol. 2001;19:1238–47.
29. Blackmon SH, Patel AR, Bruckner BA, Beyer EA, 42. Bramwell VH, Anderson D, Charette ML.
Rice DC, Vaporciyan AA, Wojciechowski Z, Correa Doxorubicin-based chemotherapy for the palliative
AM, Reardon MJ. Cardiac autotransplantation for treatment of adult patients with locally advanced or
malignant or complex primary left-heart tumors. Tex metastatic soft tissue sarcoma. Cochrane Database
Heart Inst J. 2008;35:296–300. Syst Rev. 2003;CD003293
30. Kopp HG, Patel S, Brücher B, Hartmann JT. Potential 43. O’Bryan RM, Baker LH, Gottlieb JE, Rivkin SE,
combination chemotherapy approaches for advanced Balcerzak SP, Grumet GN, Salmon SE, Moon TE,
adult-type soft-tissue sarcoma. Am J Clin Dermatol. Hoogstraten B. Dose response evaluation of Adriamycin
2008;9:207–17. in human neoplasia. Cancer. 1977;39:1940–8.
31. Chao J, Chow WA, Somlo G. Novel targeted thera- 44. Patel SR, Vadhan-Raj S, Papadopolous N, Plager C,
pies in the treatment of soft-tissue sarcomas. Expert Burgess MA, Hays C, Benjamin RS. High-dose ifos-
Rev Anticancer Ther. 2010;10:1303–11. famide in bone and soft-tissue sarcomas: results of
32. Homsi J, Daud AI. Spectrum of activity and mecha- phase II and pilot studies-dose response and sched-
nism of action of VEGF/PDGF inhibitors. Cancer ule dependence. J Clin Oncol. 1997;15:2378–84.
Control. 2007;14:285–94. 45. Patel SR, Vadhan-Raj S, Burgess MA, Plager C,
33. Ravi V, Benjamin RS. Systemic therapy for cardiac Papadopolous N, Jenkins J, Benjamin RS. Results of
sarcomas. Methodist Debakey Cardiovasc J. 2 consecutive trials of dose-intensive chemotherapy
2010;6:57–60. with doxorubicin and ifosfamide in patients with sar-
34. Ganjoo K, Jacobs C. Antiangiogenesis agents in the comas. Am J Clin Oncol. 1998;21:317–21.
treatment of soft tissue sarcomas. Cancer. 46. Wu NZ, Da D, Rudoll TL, Needham D, Whorton AR,
2010;116:1177–83. Dewhirst MW. Increased microvascular permeability
35. Kisker O, Becker CM, Prox D, Fannon M, D’Amato R, contributes to preferential accumulation of Stealth
Flynn E, Fogler WE, Sim BK, Allred EN, Pirie- liposomes in tumor tissue. Cancer Res.
Shepherd SR, Folkman J. Continuous administration of 1993;53:3765–70.
endostatin by intraperitoneally implanted osmotic pump 47. Garcia AA, Kempf RA, Rogers M, Muggia FM. A
improves the efficacy and potency of therapy in a mouse phase II study of Doxil (liposomal doxorubicin):
xenograft tumor model. Cancer Res. 2001;15:7669–74. lack of activity in poor prognosis soft tissue sarco-
36. Le Cesne A, Judson I, Crowther D, Rodenhuis S, mas. Ann Oncol. 1998;9:1131–3.
Keizer HJ, Van Hoesel Q. Randomized phase III 48. Skubitz KM. Phase II trial of pegylated-liposomal
study comparing conventional-dose doxorubicin doxorubicin (Doxil™) in sarcoma. Cancer Invest.
plus ifosfamide versus high-dose doxorubicin plus 2003;21:167–76.
ifosfamide plus recombinant human granulocyte 49. Skubitz M, Haddad PA. Paclitaxel and pegylated-
macrophage colony-stimulating factor in advanced liposomal doxorubicin are both active in angiosar-
soft-tissue sarcomas: a trial of the EORTC-STBSG. coma. Cancer. 2005;15:361–6.
J Clin Oncol. 2000;18:2676–84. 50. Eiling S, Lischner S, Busch J-O, Rothaupt D,
37. Schütte J, Mouridsen HT, Stewart W, Santoro A, van Christophers E, Hauschild A. Complete remission of
Oosterom AT, Somers R, Blackledge G, Verweij J, a radio-resistant cutaneous angiosarcoma of the
Dombernowsky P, Thomas D. Ifosfamide plus doxoru- scalp by systemic treatment with liposomal doxoru-
bicin in previously untreated patients with advanced soft bicin. Brit J Derm. 2002;147:150–3.
tissue sarcoma. The EORTC Soft Tissue and Bone 51. Verdier E, Carvalo P, Young P, Musette P, Courville P,
Sarcoma Group. Eur J Cancer. 1990;26:558–61. Joly P. Lymphangiosarcoma treated with liposomal
doxorubicin. Ann Dermatol Venerol. 2007; GK. Phase II study of sorafenib in patients with
134:760–3. metastatic or recurrent sarcomas. J Clin Oncol.
52. Belotti D, Vergani V, Drudis T, Borsotti P, Pitelli 2009;27:3133–40.
MR, Viale G, Giavazzi R, Taraboletti G. The micro- 62. Chugh R, Wathen JK, Maki RG, Benjamin RS,
tubule-affecting drug paclitaxel has anti-angiogenic Patel SR, Meyers PA, Priebat DA, Reinke DK,
activity. Clin Cancer Res. 1996;2:1843–9. Thomas DG, Keohan ML, Samuels BL, Baker LH.
53. Patel SR, Gandhi V, Jenkins J, Papadopolous N, Phase II multicenter trial of imatinib in 10 histologic
Burgess MA, Plager C, Plunkett W, Benjamin RS. subtypes of sarcoma using a Bayesian hierarchical
Phase II clinical investigation of gemcitabine in statistical model. J Clin Oncol. 2009;27:3148–53.
advanced soft-tissue sarcomas and window evalua- 63. Penel N, Marreaud S, Robin YM, Hohenberger P.
tion of dose-rate on gemcitabine triphosphate accu- Angiosarcoma: state of the art and prospectives. Crit
mulation. J Clin Oncol. 2001;19:3483–9. Rev Oncol/Hematol 2011;80:257–63.
54. Hensley ML, Maki R, Venkatraman E, Geller G, 64. Ordonez JL, Martins AS, Osuna D, Madoz-Gùrpide
Lovegren M, Aghajanian C, Sabbatini P, Tong W, J, de Alava E. Targeting sarcomas: therapeutic tar-
Barakat R, Spriggs DR. Gemcitabine and docetaxel in gets and their rational. Sem Diagn Pathol. 2008;25:
patients with unresectable leiomyosarcoma: results of 304–16.
a phase II trial. J Clin Oncol. 2002;20:2824–31. 65. Gagliardi G, Constine LS, Moiseenko V, Correa C,
55. Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard Pierce LJ, Allen AM, Marks L. Radiation dose-volume
I, Piperno-Neumann S, KerbratP, Fournier C, Taieb S, effects in the heart. Int J Radiat Oncol Biol Phis.
Jimenez M, Isambert N, Peyrade F, Chevreau C, 2010;76(3 Suppl):S77–85.
Bompas E, Brain EG, Blay JY. Phase II trial of weekly 66. Basavaraju SR, Easterly CE. Pathophysiological
paclitaxel for unresectable angiosarcoma: the effects of radiation on atherosclerosis development
AngioTax study. J Clin Oncol. 2008;26:5269–74. and progression, and the incidence of cardiovascular
56. Schlemmer M, Reichardt P, Verweij J, Hartmann JT, complications. Med Phys. 2002;29:2391–403.
Judson I, Thyss A, Hogendoorn PCW, Marreaud S, 67. Boerma M, Wang J, Wondergem J, Joseph J, Qui X,
Van Glabbeke M, Blay JY. Paclitaxel in patients with Kennedy RH, Hauer-Jensen M. Influence of mast
advanced angiosarcomas of soft tissue: a retrospec- cells on structural and functional manifestations of
tive study of the EORTC soft tissue and bone sar- radiation-induced heart disease. Cancer Res. 2005;65:
coma group. Eur Jof Cancer. 2008;44:2433–6. 3100–7.
57. Bocci G, Nicolaou KC, Kerbel RS. Protracted low- 68. Schultz-Hector S, Trott KR. Radiation-induced car-
dose effects on human endothelial cell proliferation diovascular diseases: is the epidemiologic evidence
and survival in vitro reveal a selective anti-angio- compatible with the radiobiologic data? Int J Radiat
genic window for various chemotherapeutic drugs. Oncol Biol Phys. 2007;67:10–8.
Cancer Res. 2002;62:6938–43. 69. Goitein M. Organ and tumor motion: an overview.
58. Browder T, Butterfield CE, Kräling BM, Shi B, Semin Radiat Oncol. 2004;14:2–9.
Marshall B, O’Reilly MS. Anti-angiogenic schedul- 70. De Paoli A, Lestuzzi C, Santini F, Boz G, Innocente
ing of chemotherapy improves efficacy against R, Buonadonna A, Canzonieri V, Frustaci S. Primary
experimental drug-resistant cancer. Cancer Res. cardiac sarcomas: experience with an evolving mul-
2000;60:1878–86. tidisciplinary approach with focus on the radiation
59. Verweij J, Lee SM, Ruka W, Buesa J, Coleman R, therapy component. In: Proceedings of the 16th con-
van Hoessel R, Seynaeve C, di Paola ED, van nective tumors oncology society annual meeting,
Glabbeke M, Tonelli D, Judson IR. Randomized 2010; #60. p. 118.
phase II study of docetaxel versus doxorubicin in 71. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni
first-line and second-line chemotherapy for locally L. Anthracyclines: molecular advances and pharma-
advanced or metastatic soft tissue sarcomas in adults: cologic developments in antitumor activity and car-
a study of the European Organization for Research diotoxicity. Pharmacol Rev. 2004;56:185–229.
and Treatment of Cancer Soft Tissue and Bone 72. Simůnek T, Stérba M, Popelová O, Adamcová M,
Sarcoma Group. J Clin Oncol. 2000;18:2081–6. Hrdina R, Gersl V. Anthracycline-induced cardio-
60. George S, Merriam P, Maki RG, Van den Abbeele toxicity: overview of studies examining the roles of
AD, Yap JT, Akhurst T, Harmon DC, Bhuchar G, oxidative stress and free cellular iron. Pharmacol
O’Mara MM, D’Adamo DR, Morgan J, Schwartz Rep. 2009;61:154–71.
GK, Wagner AJ, Butrynski JE, Demetri GD, Keohan 73. Senkus E, Jassem J. Cardiovascular effects of sys-
ML. Multicenter phase II trial of sunitinib in the temic cancer treatment. Cancer Treat Rev. 2011;37:
treatment of nongastrointestinal stromal tumor sar- 300–11.
comas. J Clin Oncol. 2009;27:3154–60. 74. Bristow MR, Mason JW, Billingham ME, Daniels
61. Maki RG, D’Adamo DR, Keohan ML, Saulle M, JR. Dose-effect and structure-function relationships
Schuetze SM, Undevia SD, Livingston MB, Cooney in doxorubicin cardiomyopathy. Am Heart J.
MM, Hensley ML, Mita MM, Takimoto CH, Kraft 1981;102:709–18.
AS, Elias AD, Brockstein B, Blachère NE, Edgar 75. Swain SM, Whaley FS, Ewer MS. Congestive
MA, Schwartz LH, Qin LX, Antonescu CR, Schwartz heart failure in patients treated with doxorubicin:
a retrospective analysis of three trials. Cancer. than anthracyclines, fluoropyrimidines and trastu-
2003;97:2869–79. zumab). Bull Cancer. 2004;91:S174–84.
76. Singal PK, Iliskovic N. Doxorubicin-induced cardi- 88. Tascilar M, Loos WJ, Seynaeve C, Verweij J, Sleijfer
omyopathy. N Engl J Med. 1998;339:900–5. S. The pharmacologic basis of ifosfamide use in
77. Menna P, Salvatorelli E, Minotti G. Cardiotoxicity adult patients with advanced soft tissue sarcomas.
of antitumor drugs. Chem Res Toxicol. 2008;21: Oncologist. 2007;12:1351–60.
978–89. 89. Sayed-Ahmed MM, Darweesh AQ, Fatani AJ.
78. van Dalen EC, Caron HN, Dickinson HO, Kremer Carnitine deficiency and oxidative stress provoke
LC. Cardioprotective interventions for cancer cardiotoxicity in an ifosfamide-induced Fanconi syn-
patients receiving anthracyclines. Cochrane Database drome rat model. Oxid Med Cell Longev.
Syst Rev. 2008;16:CD003917. 2010;3:266–74.
79. Grenader T, Goldberg A, Hadas-Halperin I, Gabizon 90. Raisch DW, Campbell W, Garg P, Qureshi ZP,
A. Long-term response to pegylated liposomal Bookstaver PB, Norris LAB, Bennet CL.
doxorubicin in patients with metastatic soft tissue Description of anaphylactic reactions to paclitaxel
sarcomas. Anticancer Drugs. 2009;20:15–20. and docetaxel reported to the FDA, with a focus
80. Lipshultz SE, Scully RE, Lipsitz SR, Sallan SE, on the role of premedication. Expert Opin Drug
Silverman LB, Miller TL, Barry EV, Asselin BL, Saf. 2011;10:521–8.
Athale U, Clavell LA, Larsen E, Moghrabi A, Samson Y, 91. Mourad JJ, des Guetz G, Debbabi H, Levy BI. Blood
Michon B, Schorin MA, Cohen HJ, Neuberg DS, pressure rise following angiogenesis inhibition by
Orav EJ, Colan SD. Assessment of dexrazoxane as a bevacizumab. A crucial role for microcirculation.
cardioprotectant in doxorubicin-treated children with Ann Oncol. 2008;19:927–34.
high-risk acute lymphoblastic leukaemia: long-term 92. Vaklavas C, Lenihan D, Kurzrock R, Tsimberidou
follow-up of a prospective, randomised, multicentre AM. Anti-vascular endothelial growth factor thera-
trial. Lancet Oncol. 2010;11:950–61. pies and cardiovascular toxicity: what are the impor-
81. Smith LA, Cornelius VR, Plummer CJ, Levitt G, tant clinical markers to target? Oncologist. 2010;15:
Verrill M, Canney P, Jones A. Cardiotoxicity of 130–41.
anthracycline agents for the treatment of cancer: sys- 93. Syrigos KN, Karapanagiotou E, Boura P, Manegold
tematic review and meta-analysis of randomised C, Harrington K. Bevacizumab-induced hyperten-
controlled trials. BMC Cancer. 2010;10:337. sion: pathogenesis and management. BioDrugs.
82. Tallaj JA, Franco V, Rayburn BK, Pinderski L, Benza 2011;25:159–69.
RL, Pamboukian S, Foley B, Bourge RC. Response 94. Force T, Kolaja KL. Cardiotoxicity of kinase inhibi-
of doxorubicin-induced cardiomyopathy to the cur- tors: the prediction and translation of preclinical
rent management strategy of heart failure. J Heart models to clinical outcomes. Nat Rev Drug Discov.
Lung Transplant. 2005;24:2196–201. 2011;10:111–26.
83. Cardinale D, Colombo A, Sandri MT, Lamantia G, 95. Hasinoff BB, Patel D. Mechanisms of myocyte cyto-
Colombo N, Civelli M, Martinelli G, Veglia F, toxicity induced by the multikinase inhibitor
Fiorentini C, Cipolla CM. Prevention of high-dose sorafenib. Cardiovasc Toxicol. 2010;10:1–8.
chemotherapy-induced cardiotoxicity in high-risk 96. Hasinoff BB, Patel D. The lack of target specificity
patients by angiotensin-converting enzyme inhibi- of small molecule anticancer kinase inhibitors is cor-
tion. Circulation. 2006;114:2474–81. related with their ability to damage myocytes in vitro.
84. Cardinale D, Colombo A, Lamantia G, Colombo N, Toxicol Appl Pharmacol. 2010;249:132–9.
Civelli M, De Giacomi G, Rubino M, Veglia F, 97. Berry GJ, Jorden M. Pathology of radiation and
Fiorentini C, Cipolla CM. Anthracycline-induced anthracycline cardiotoxicity. Pediatr Blood Cancer.
cardiomyopathy: clinical relevance and response to 2005;44:630–7.
pharmacologic therapy. J Am Coll Cardiol. 98. Fajardo LF, Stewart JR. Capillary injury preceding
2010;55:213–20. radiation-induced myocardial fibrosis. Radiology.
85. Wells QS, Lenihan DJ. Reversibility of left ventricu- 1971;101:429–33.
lar dysfunction resulting from chemotherapy: can 99. Marks LB, Yu X, Prosnitz RG, Zhou SM,
this be expected? Prog Cradiovasc Dis. Hardenbergh PH, Blazing M, Hollis D, Lind P, Tisch
2010;53:140–8. A, Wong TZ, Borges-Neto S. The incidence and
86. Quezado ZMN, Wilson WH, Cunnion RE, Parker functional consequences of RT-associated cardiac
MP, Reda D, Bryant G, Ognibene FP. High-dose perfusion defects. Int J Radiat Oncol Biol Phys.
ifosfamide is associated with severe, reversible car- 2005;63:214–23.
diac dysfunction. Ann Int Med. 1993;118:31–6. 100. Veinot JP, Edwards WD. Pathology of radiation-
87. Saintigny P, Chouhania K, Charniot J-C, Breau JL. induced heart disease: a surgical and autopsy study
Cardiovascular toxicity of some cancer agents (others of 27 cases. Hum Pathol. 1996;27:766–75.
Novelties in Immunohistochemical
and Molecular Study of Cardiac 13
Tumors
Augusto Orlandi and Luigi Giusto Spagnoli
matrix [2]. Myxoma usually arises from the

Introduction inter-atrial septum, more frequently on the left side
[1, 2]. The histogenesis of cardiac myxoma was
Cardiac tumors are rare entities [1, 2]. Because of for a long time considered uncertain, because of
the rarity, it is difficult to investigate systemati- the nature of the morphological and immunohis-
cally large series of cardiac tumors using ancillary tochemical findings obtained after the character-
or biomolecular and experimental methods of ization of this tumor. In fact, a variable expression
investigation. As a consequence, scarce innovative of proteins typical of different adult cell pheno-
information is available concerning the histogene- types has been reported, even in the same tumor,
sis of the majority of cardiac tumors. Myxomas suggesting an epithelial, endothelial, myogenic,
are the most frequent neoplasms, accounting for myofibroblastic, or neural origin, respectively [3–
50% of all tumors [1, 2], and the most investigated 10]. In adult myocardium, two sarcomeric actins,
primary cardiac tumor. Nevertheless, the origin of a-cardiac and a-skeletal actin, are co-expressed
myxoma remains uncertain. In this chapter, we and represent the predominant isoforms [11]; in
summarize the most recent novelties in the biomo- addition, a-smooth muscle actin (a-actin) is tran-
lecular, immunohistochemical and genetic inves- siently observed in cardiomyocytes during the
tigation of primary cardiac tumors. early stage of fetal cardiac development [12]. In
Table 13.1 are reported the comparisons between
microscopic and immunohistochemical findings
Cardiac Myxoma (as percentages of positive cardiac myxoma cells)
in a series of thirty tumors [13]. Although cardiac
Novelties in Immunohistochemical myxomas variably expressed vimentin, Notch1,
Findings CALB2, and smooth muscle antigens such as
a-actin and caldesmon were the most frequently
Myxoma is the most frequent primary tumor of the observed with a diffuse cytoplasmic immunoreac-
heart [1]. Its name derives from myxoid appear- tivity, followed by CD34. It is worth noting that
ance of a mucopolysaccharide-rich extracellular a-cardiac actin was observed in a few cases and
a-skeletal actin was always absent. Single or
multinucleated cells were CD34 positive mainly in
A. Orlandi, M.D. (*) • L.G. Spagnoli, M.D. the superficial areas of tumors, whereas interstitial
Department of Biomedicine and Prevention, or perivascular cells were more a-smooth muscle
Institute of Anatomic Pathology,
actin positive. The immunophenotype of vascular
Tor Vergata University of Rome,
Via Montpellier, Rome 00133, Italy structures of cardiac myxoma has been also inves-
e-mail: orlandi@uniroma2.it tigated [13]. As concerning the complex vascular
184 A. Orlandi and L.G. Spagnoli
Table 13.1 Comparison of microscopic and immunohis- myxoma were of two different types: the first,
tochemical features in a series of 30 cardiac myxomas larger and with a thick wall, covered by CD34
Microscopic findings (% of positive cases) positive endothelial-like cells with a-actin positive
Smooth 63.3 parietal cells, were observed throughout the entire
Irregular surface 36.7 myxoma tissue; the second type, smaller and
Superficial collagenization 43.3 mainly at the parietal edge, resembled morpho-
Myxomatous areas (>50%) 56.6 logically and immunohistochemically the normal
Ki-67 positive cells (>5%) 6.7 atrial vasculature. Finally, confocal microscopy
Calcification 6.7
well documents the presence of CD34 and a-actin
Small superficial thrombi 40
positive myxoma cells; rare myxoma cells, includ-
Extramedullary hematopoiesis 6.7
ing multinucleated cells, focally co-expressed both
Ring structures 80
proteins (Fig. 13.2), suggesting a precursor or an
Vascular-like lacunae 16.7
Arterial-like vessels 60
intermediate cell phenotype [13].
Glandular structures 0.6
Immunohistochemical findings
Cytokeratins 6.7 Biomolecular Analysis
Vimentin 90 of Cardiac Myxomas
a-Smooth muscle actin 83.3
a-Cardiac actin 10 The availability of methods of investigation of
a-Skeletal actin 0 gene expression, in particular reverse tran-
Notch1 86.7 scriptase-polymerase chain reaction (RT-PCR)
Calretinin 86.7 and Real Time-PCR, may help to better charac-
CD34 66.7 terize phenotypic features of cardiac tumor
Factor VIII 36.7 cells. Unfortunately, the optimal results are
Caldesmon 86.7 obtained after mRNA extraction from fresh tis-
Tenascin C 80 sue and, for their intrinsic rarity, a systematized
MMP-1 36.7
tissue banking of cardiac tumor tissues is quite
MMP-2 36.7
difficult. When possible, gene transcripts reca-
TIMP-1 36.7
pitulating specific phenotypes can be also useful
S-100 13.3
to trace differentiation of tumor cells. In cardiac
Flt-1 26.7
c-kit 0
myxoma, PCR analysis performed on RNA
a
extracted from frozen tissue from eight consec-
Modified from Orlandi et al. [13].
utive cases of cardiac myxoma [13] revealed
CALB2 (calretinin) and Sox9 transcripts in all
cases, Notch1 and NFATcI transcripts in 87.5
and 37.5% of cases, respectively, whereas all
structures, enlarged ring structures are in the cases were negative for ErbB3 and Wilms’
majority of cases CD34 positive and only focally tumor transcription factor (Fig. 13.3).
a-actin positive. Lacunae, other complex vascular-
like structures of cardiac myxoma, are character-
ized by wide vascular-like spaces covered by Myxoma Cell Phenotype and Clinical
single or multilayered CD34 positive and a-actin Behavior of Cardiac Myxomas
negative cells, whereas parietal cells are positive
for the myocytic marker a-actin, suggesting an Cardiac myxomas are benign tumors which are
endothelial and pericyte-like differentiation, unable to infiltrate the myocardium or give rise
respectively (Fig. 13.1). Rarely, parietal cells of to metastases [1, 2]. Nevertheless, they are con-
ring structures were also focally a-cardiac actin sidered “clinically malignant” tumors because
positive. Thick arterial-like structures of cardiac of their susceptibility to embolize to distant
13 Novelties in Immunohistochemical and Molecular Study of Cardiac Tumors 185
Fig. 13.1 Immunohistochemical characterization of vas- positive cells. (c, d) Elongated multilayered structures, with
cular complex structures of cardiac myxoma. (a, b) (c) abundant CD34 positive and (d) rare parietal a-smooth
Complex structures from wide vascular-like spaces with a muscle actin positive cells. Diaminobenzidine as chromo-
thin wall constituted by one or more layers of flattened (a) gen; original magnification, ×125
CD34 positive and (b) focally a-smooth muscle actin
Fig. 13.2 Co-expression of endothelial and myogenic green) of cardiac myxoma cell, sometimes multinucleated;
markers in cardiac myxoma. Immunofluorescent staining merged image (right) shows co-expression of both endothe-
of a-smooth muscle actin (left, red) and CD34 (middle, lial and myocytic antigens. Original magnification, ×400
protein levels the extrinsic Fas/FasL-dependent

final common apoptotic pathway of myxoma
cells [19]. More recently, a series of 27 left
atrial myxomas, 10 of them with clinical
signs of peripheral embolism, have been inves-
tigated by several methods, documenting in
embolic myxomas higher expression and
activity of matrix metalloproteinases (MMPs),
in particular MT1-MMP, pro-MMP-2, and pro-
MMP-9, whereas pro-MMP-1, MMP-3, and
TIMP-1 levels were similar to those of non-
embolic tumors [20]. MMPs are a large family
of zinc-dependent proteolytic enzymes that
degrade the extracellular matrix in both normal
and pathological processes [21–23]. MMPs are
released into the extracellular milieu in a proen-
zyme state or membrane-bound enzymes that
undergo intracellular activation and are proteo-
litically active when inserted into the cell mem-
brane. Increased expression of MMPs associated
more frequently with the irregular or polypoid
aspect of cardiac myxomas [20]. Consequently,
it is possible to hypothesize that increased
MMP expression and activity can induce a
remodeling of tumor extracellular matrix, with
Fig. 13.3 Primitive mesenchymal markers gene expres- a consequent increase of friability and, conse-
sion in cardiac myxoma. Agarose gel after ethidium bro- quently, of the risk of embolism of cardiac
mide staining documents RT-PCR analysis of transcripts
from eight consecutive cardiac myxomas mRNA showing
myxoma. Nevertheless, in some cases of non-
variable CD34, MMP-2, TIMP-1, Sox9, CALB2, and embolic irregular myxomas, MMP expression
Notch1 transcripts, while ErbB3 and WT1 transcripts are did not significantly differ from non-embolic
absent; b2microglobulin is used as housekeeping gene. smooth tumors, suggesting that embolism is not
Modified from Orlandi et al. [13]
the natural consequence of the irregular macro-
scopic appearance. Moreover, these studies
organs [1, 2, 14]. As a matter of fact, clinical in vivo do not clarify if increased MMP activity
signs of tumor embolism represent the primary is an intrinsic feature of myxoma cells or, alter-
manifestation in 30–50% of cases. Since most natively, it is related to an increased suscepti-
myxomas are left atrium-located, emboli preva- bility to locally delivered cytokines [17].
lently involve peripheral districts, in particular Nevertheless, embolic myxoma cells retain
cerebral arteries, including retinal artery [1, 2, higher MT1-MMP and pro-MMP-2 levels in
14]. Echocardiographic polypoid and irregular basal condition and after stimulation with IL-1b
macroscopic aspects, changes in the composi- and IL-6 in vitro [20].
tion of the myxomatous matrix, as well as the
autocrine production of IL-6 have been consid-
ered [14–17]. Another hypothesis considers The Origin of Cardiac Myxoma:
apoptosis as relevant for myxoma tissue remod- An Update
eling and, consequently, for the clinical behav-
ior of these cardiac tumors [18]. Successively, The heterogeneous phenotype of myxoma cells
other researchers identified at both mRNA and gave origin to several interpretations concerning
the histogenesis of cardiac myxoma. The pres- the adult heart, a-cardiac actin is the major
ence of endothelial marker and cytoplasmic neu- isoform and uniformly expressed [12]. The mes-
ropeptides such as protein gene product 9.5, enchymal origin and the subsequent endothelial
S100 protein and neuron-specific enolase in differentiation are further supported from ultra-
more than half of a series of cardiac myxomas structural study of cardiac myxomas [20, 29,
supports the hypothesis that myxoma cells origi- 30]. The presence of a limited number of myx-
nate from pluripotent mesenchymal cells capable oma cells co-expressing the primitive endothe-
of neural and endothelial differentiation [9]. lial and myocytic markers CD34 and a-actin
Another explanation for heterogeneous differen- supports the hypothesis that myxoma cells can
tiation in cardiac myxoma is its origin from a derive from a common cardiac early precursor
pluripotential cell or from a subendothelial vas- cell [25]. The origin of cardiac myxoma in atrial
iform reserve cell, on the basis of the expression cavity in association with fibrous septa or fossa
of transcripts characteristic of cardiac cushion ovalis suggests a relationship with fibrous car-
development and/or primitive cardiac mesenchy- diac structures and their development [1, 2].
mal differentiation [3, 4, 24]. Some morphologic Endocardial cushions are the precursors of
homologies between cardiac myxoma cells and mature heart valves and cardiac septa [31–34].
those of embryonic cardiac cushion cells support Embryonic endocardial cells of the outflow tract
this hypothesis. A cardiomyogenic derivation of and atrioventricular canal change their phenotype
cardiac myxomas was based on the finding of from endothelial to mesenchymal cells during the
transcripts for Nkx2.5/Csx, typical of the cardiac so-called endothelial–mesenchymal transforma-
homeobox gene, recapitulating a primitive car- tion, leading to cardiac septation and mature valve
diomyocytic phenotype and supporting an formation. During this phase, embryonic endocar-
embryonic cardiomyocytic progenitor cell as dial cells progressively express a-smooth muscle
precursor [25]. Although Nkx2.5/Csx encodes actin and lose endothelial antigens [33]. Cardiac
for a gene required for specification of cardiac jelly, an acellular matrix rich in fibronectin and
precursor cells, its expression is maintained proteoglycans, separates the primitive endocar-
throughout development [25]. Moreover, Nkx2.5/ dium from myocardium and favors the initiation
Csx is documented during development of other of the endothelial–mesenchymal transformation
tissues, including skeletal myoblasts and pro- [31–34]. Cardiac jelly appears very similar to
motes neuronal differentiation in vitro [26, 27]. extracellular matrix of cardiac myxoma. Transient
This explains the previously reported expression ectopic activation of Notch1 in zebrafish embryos
of neural markers [9] as a demonstration of a leads to hypercellular cardiac valves, whereas its
possible neurogenic origin of cardiac myxoma inhibition prevents valve development [35]. Notch
cells. Investigation of actin isoform expression activation in endothelial cells determines down-
can be useful to trace the origin of cardiac myx- regulation of endothelial markers and upregula-
oma cells. In particular, the diffuse presence of tion of mesenchymal ones, including a-smooth
a-smooth muscle actin, the paucity of a-cardiac muscle actin and fibronectin [35]. Moreover,
actin, and the absence of a-skeletal actin isoform RT-PCR shows in cardiac myxomas the presence
expression have been described in cardiac myxo- of Sox9 and NFATcI transcripts [20]. Sox9 has
mas [20]; a-smooth muscle actin is reported to been indicated to play an essential role in early
be transiently expressed in human cardiomyo- phases of endocardial cushion differentiation,
cytes during early stages of fetal development when endocardial endothelial cells migrate into
[28]. This finding supports that myxoma cells the cardiac jelly [36]. NFATcI expression is criti-
are phenotypically reconducible to a more primi- cal during signal-transduction processes required
tive cardiac progenitor or primordial cardiac for cardiac valve formation and is normally abol-
stem cell. In fact, in the 20-week-old fetal heart, ished after endocardial cushion cell migration
a time when septation is complete and the heart [37]. The presence of phenotypic markers of
exhibits all the morphological characteristics of endothelial–mesenchymal transformation may
be related to the persistence of developmental

remnants or stem cells in adult heart or, alterna- Genetic Features of Cardiac
tively, to de novo re-expression of a develop- Non-myxomatous Tumors
mental phenotype in adult cardiac cells.
Non-myxomatous cardiac benign tumors are rare
and sometimes arising in the setting of genetic
Carney’s Complex syndromes (Table 13.2). Molecular genetic inves-
tigation of cardiac primary non-myxomatous
Carney’s complex is a neuroendocrine-cardiac tumors has provided relevant information to elu-
syndrome characterized by (a) familial recur- cidate many mechanisms of cardiac cell develop-
rent myxomas; (b) pigmented skin lesions, mental growth. Cytogenetic studies have targeted
schwannomas, and recurrent mucocutaneous candidate chromosomal loci that may be per-
myxomas; and (c) endocrine abnormalities, turbed during the pathogenesis of cardiac lipoma.
including Cushing syndrome and acromegaly, Common cutaneous lipomas have been associ-
and malignancies [38]. One-third of the patients ated with rearrangements of chromosome band
with Carney’s syndrome display at presentation 12q15. Cytogenetic analysis of an unusual giant
mucocutaneous myxomas of the eyelid, external cardiac lipoma in a patient with a history of mul-
ear canal, breast, and oropharynx. About two- tiple lipomatosis demonstrated no abnormalities
thirds of these patients have cardiac tumors, and of chromosome 12, but a translocation (2, 19)
75% various skin pigmented lesions, including (p13; p13.2) [48]. Rhabdomyoma, the most com-
blue nevi and café au lait spots [39]. Carney’s mon pediatric cardiac neoplasm, is frequently
complex is characterized by an autosomal domi- associated with tuberous sclerosis by mutations
nant transmission with incomplete penetrance. in the tuberous sclerosis complex-1 and - 2 that
Linkage studies have revealed genetic foci at codify two proteins, hamartin and tuberin.
2p16 and 17q22–24 [40, 41]. Among the fami- Tuberous sclerosis complex is a genetic disorder
lies mapping to 17q, mutations in the gene characterized by the formation of hamartomas
encoding the protein kinase A type I-a regula- in multiple organs, including rhabdomyomas in
tory subunit have been identified [42]. In patients the heart [49]. Hamartin and tuberin antagonize
with Carney’s complex, cardiac tumors recur in the mammalian target of rapamycin signaling
more than 20% of cases, and account for more pathway, thus regulating cell growth and prolif-
than 50% of causes of death [39]. Consequently, eration. Nonsense mutations in the hamartin and
patients with established Carney’s complex tuberin genes have been identified as causative
require vigorous screening for cardiac tumors, of cardiac rhabdomyomas [49]. Many complica-
in particular to exclude multiple locations. tions have been reported in association with
Routinary echocardiographic screening of the nevoid basal cell carcinoma syndrome, also
first-degree relatives seems appropriate for known as Gorlin–Goltz or Gorlin syndrome
familial myxomas [43]. [50, 51]. The hallmark of this syndrome is the
Table 13.2 Cardiac tumors and related genetic syndromes

Genetic syndrome(s) Gene(s) mutation Chromosome Refs.
Rhabdomyoma Tuberous sclerosis TSC1/TSC2 9q34/16p13 [44]
Myxoma Carney complex PRKAR1A 2p16, 7q22, q17 [20, 40, 41,
45]
Fibroma Gorlin–Goltz syndrome PTCH1 9q22.3 [46]
Paraganglioma Neurofibromatosis type 1, Von VHL NF1 RET SDHB SDHC 3p25, 17q11, [47]
Hippel–Lindau syndrome, 2B SDHD 1p36, 10q11,
Familial pheochromocytoma– q21, 11q23
paraganglioma syndrome
Table 13.3 Main immunohistochemical findings in cardiac sarcomas1

a-Smooth muscle
CD34 FVIII CD31 S100 actin Desmin CK Vimentin Myogenin
Angiosarcoma + + + − − − R* + −
Undifferentiated − − − − R − R + −
pleomorphic sarcoma
Rhabdomyosarcoma − − − − + + − + +
Fibrosarcoma − − − − R − − + −
Leiomyosarcoma − − − − + + R − +
Synovial sarcoma − − − − R − + + −
Liposarcoma − − − + − − − + −
FVIII factor VIII, CK cytokeratins, R rare and focal, + positive, − negative, asterisk diffusely positive in epithelioid
variant
8
Modified from Orlandi et al. [52]
presence of multiple basal cell carcinomas, primary cardiac sarcomas existed. The difficulty
which may appear early in infancy. Other asso- derived from the rarity and lack of systematic
ciated features may include craniofacial, central studies, with only a few series of cardiac sarco-
nervous system, musculoskeletal, and genitouri- mas in the literature. Virtually, all soft tissue
nary anomalies. Approximately 3% of cases are sarcoma types have also been found to arise in
associated with cardiac fibromas, which may the heart. The recent WHO classification sys-
present later during adulthood rather than the tem of cardiac tumors proposed in 2004 [54] is
typical infancy or childhood period [51]. largely based on the soft tissue classification
Consequently, cardiac fibromas are generally counterpart and only the most frequent malig-
not considered part of the syndrome and judged nant entities are listed, since the majority of
as minor diagnostic criteria [50]. Nevertheless, cardiac sarcomas have limited areas with mor-
the investigation of Gorlin syndrome has shed phologically recognizable differentiation.
light on the etiology of cardiac fibromas. It is Moreover, despite a careful immunohistochem-
caused by mutations in the PTCH1 gene, which ical investigation, they frequently lack tissue-
acts as a cell cycle regulator and regulates cell specific antigens.
growth, commitment, and differentiation [51].
Immunohistochemical Features
Cardiac Sarcomas of Cardiac Sarcomas
Introduction Despite a careful immunohistochemical investi-

gation, cardiac sarcomas generally lack tissue-
Primary cardiac sarcomas are by definition specific antigens. Main immunohistochemical
malignant neoplasms deriving from mesenchy- findings are schematically reported in Table 13.3
mal cells and confined to the heart at the time of and can be useful in supporting morphological
diagnosis. Most cardiac sarcomas have the same criteria of diagnosis in some specific cases.
histological appearance as their soft tissue Angiosarcoma is microscopically characterized
counterpart. Primary heart sarcomas are excep- by vascular differentiation with channels covered
tionally rare and represent approximately 10% by endothelial cells exhibiting marked atypia.
of total primary cardiac tumors [2, 52]; cardiac Factor VIII or CD34 positive immunodetection of
metastases at autopsy are 20–40 times more malignant cells represents useful markers of
frequent than primary tumors [53]. For many endothelial differentiation; moreover, cytokera-
years, no universally accepted classification of tins can be diffusely positive in epithelioid areas
of angiosarcoma [2]. Undifferentiated sarcoma is specific genetic mutations reported. This is

defined as a cardiac sarcoma with no specific his- likely due to the rarity and consequent absence
tological pattern or undifferentiated [53]. of a systematically characterized large series
Nowadays, undifferentiated sarcoma is consid- of cardiac sarcomas. Moreover, as concerning
ered synonymous with pleomorphic malignant genetic characterization of cardiac sarcomas,
fibrous histiocytoma [54]. Undifferentiated sar- K-ras mutation and the absence of p53 muta-
coma must be distinguished from embryonal tions have been observed in three cases of
rhabdomyosarcoma and metastatic small cell can- angiosarcomas and two of rhabdomyosarco-
cer. Immunostaining is crucial, epithelial, neural, mas [59]. p53 mutations in two primary car-
or endothelial markers being usually negative and diac angiosarcomas have been reported [60].
vimentin typically positive; high grade undiffer- Cytogenetic features can represent a useful
entiated sarcomas can exhibit focal a-actin posi- diagnostic tool and can be detected by using
tive areas, but the latter are generally limited in reverse transcriptase-polymerase chain reac-
their extension [54]. Leiomyosarcoma is a malig- tion or fluorescence in situ hybridization tech-
nant tumor showing phenotypic and ultrastructural niques. Accordingly, synovial sarcomas
smooth muscle differentiation. Immunostaining typically harbor t(X; 18)(p21.2; q11.2) result-
for desmin and a-actin is usually diffusely posi- ing in SS18-SSX1 fusion transcripts, including
tive, whereas epithelial, vascular, and neural the reported unique case with a cardiac local-
markers are negative [55, 56]. Rhabdomyosarcoma ization in the examined series [61]. The same
is considered as a malignant tumor showing SYT-SSX1 fusion transcript identified by
striated muscle differentiation [2, 54]. Rhabdomy- molecular genetic studies has been also
osarcoma usually arises in the ventricular wall reported in two cases of primary cardiac syn-
and is microscopically composed of small cells ovial sarcoma arising in left atrium and ven-
with the presence of recognizable rhabdomyo- tricle and on the anterior mitral leaflet [62, 63].
blasts with the characteristic cross striations by Cytogenetic analysis has been reported to help
Masson’s trichrome and a diffuse desmin positive to distinguish low-grade fibromyxoid sarcoma
immunostaining [2, 57]. Rhabdomyosarcoma can from either more benign or more malignant
express other muscle markers, including myo- tumor types [64]. Cytogenetic investigation
genin, myoD1, sarcomeric actin, muscle-specific also identified a recurrent balanced transloca-
actin, and myoglobin. Among these, myogenin tion t(7; 16)(q32–34; p11), later shown by
and myoD1 seem to be more specific [58]. molecular genetic approaches to result in a
Synovial sarcoma is a biphasic malignant tumor FUS/CREB3L2 fusion gene. Reverse tran-
usually located in the atria or pericardial surface. scriptase-polymerase chain reaction analysis
The latter localization should be considered for disclosed a FUS/CREB3L2 fusion transcript in
distinction from malignant mesothelioma. In the 96% of cases classified as low-grade
heart, the monophasic variant of synovial sar- fibromyxoid sarcoma after the histological
coma is more common. A differential diagnosis reevaluation and from which RNA of sufficient
between malignant mesothelioma and synovial quality could be extracted, whereas a FUS/
sarcoma may be challenging on the basis of mor- CREB3L2 fusion transcript was absent in other
phological aspect and immunophenotype, both tumor types [65]. The proteins encoded by a
being positive for cytokeratins, calretinin, and CREB3L1 and CREB3L2 genes belong to the
vimentin [54]. basic leucine-zipper family of transcription
factors. A similar t(7;16)(q32–34; p11) trans-
location by FISH analysis was documented
Genetic Features of Cardiac Sarcomas in a primary intracardiac large low-grade
fibromyxoid sarcoma of the right atrium [65].
At present, the molecular histogenesis of car- Cytogenetic and molecular genetic studies
diac sarcomas is poorly known and there are no performed in one case [66] of pleomorphic
malignant fibrous histiocytoma removed from 11. Vandekerckhove J, Bugaisky G, Buckingham M.

the left atrium of a 15-year-old girl [65] Simultaneous expression of skeletal muscle and heart
actin proteins in various striated muscle tissues and
revealed several alterations previously associ- cells. A quantitative determination of the two actin
ated with adult malignant fibrous histiocytoma, isoforms. J Biol Chem. 1986;261:1838–43.
including abnormalities of 11p11 and 19p13 12. Suurmeijer AJ, Clement S, Francesconi A, Bocchi L,
chromosomal bands. Moreover, pleomorphic Angelini A, Van Veldhuisen DJ, Spagnoli LG, Gabbiani
G, Orlandi A. Alpha-actin isoform distribution in normal
malignant fibrous histiocytoma demonstrated and failing human heart: a morphological, morphomet-
homogeneously staining regions and double ric, and biochemical study. J Pathol. 2003;199:387–97.
minute chromosomes, in particular the 13. Orlandi A, Ciucci A, Ferlosio A, Genta R, Spagnoli
co-amplification of the 12q13–14 chromosome; LG, Gabbiani G. Cardiac myxoma cells exhibit
embryonic endocardial stem cell features. J Pathol.
the latter amplicon was not previously detected 2006;209:231–9.
in pediatric malignant fibrous histiocytoma. 14. Ha JW, Kang WC, Chung N, Chang BC, Rim SJ,
This cytogenetic and molecular genetic evi- Kwon JW, Jang Y, Shim WH, Cho SY, Kim SS, Cho
dence suggests that pediatric and adult malig- SH. Echocardiographic and morphologic characteris-
tics of left atrial myxoma and their relation to sys-
nant fibrous histiocytoma, although temic embolism. Am J Cardiol. 1999;83:1579–82.
histogenetically related, are distinct malignan- 15. Kairemo KJ, Blomqvist CP, Miettinen M. Cardiac
cies [66]. myxomas. N Engl J Med. 1996;334:1407–8.
16. Negishi M, Sakamoto H, Sakamaki T, Ishikawa O,
Kanda T, Tamura J, Kurabayashi M, Nagai R.
Disaccharide analysis of glycosaminoglycans synthe-
References sized by cardiac myxoma cells in tumor tissues and in
cell culture. Life Sci. 2003;73:849–56.
1. Reynen K. Cardiac myxomas. N Engl J Med. 17. Parissis JT, Mentzikof D, Georgopoulou M,
1995;333:1610–7. Gikopoulos M, Kanapitsas A, Merkouris K, Kefalas
2. Burke AP, Virmani R. Tumors of the heart and great C. Correlation of interleukin-6 gene expression to
vessels. In: Burke AP, Virmani R, editors. Atlas of immunologic features in patients with cardiac myxo-
tumor pathology. 3rd ed. Washington DC: Armed mas. J Interferon Cytokine Res. 1996;16:589–93.
Forced Institute of Pathology; 1996. p. 121–46. 18. Suzuki M, Hamada M, Hiwada K. Apoptosis in car-
3. Lie JT. The identity and histogenesis of cardiac myxo- diac myxoma. Ann Intern Med. 2000;132:681.
mas. A controversy put to rest. Arch Pathol Lab Med. 19. Liu CC, Jung SM, Orlandi A, Yeh TS, Lin YS, Shiu
1989;113:724–6. TF, Wu HH, Chu JJ, Lin PJ, Chu PH. The Fas-
4. Tazelaar HD, Locke TJ, McGregor CG. Pathology of mediated apoptotic pathway in cardiac myxoma. Int J
surgically excised primary cardiac tumors. Mayo Clin Surg Pathol. 2010;18:493–8.
Proc. 1992;67:957–65. 20. Orlandi A, Ciucci A, Ferlosio A, Pellegrino A, Chiariello
5. Boxer ME. Cardiac myxoma: an immunoperoxidase L, Spagnoli LG. Increased expression and activity of
study of histogenesis. Histopathology. 1984;8:861–72. matrix metalloproteinases characterize embolic cardiac
6. Goldman BI, Frydman C, Harpaz N, Ryan SF, myxomas. Am J Pathol. 2005;166:1619–28.
Loiterman D. Glandular cardiac myxomas. Histologic, 21. Oh J, Takahashi R, Kondo S, Mizoguchi A, Adachi E,
immunohistochemical, and ultrastructural evidence of Sasahara RM, Nishimura S, Imamura Y, Kitayama H,
epithelial differentiation. Cancer. 1987;59:1767–75. Alexander DB, Ide C, Horan TP, Arakawa T, Yoshida H,
7. Govoni E, Severi B, Cenacchi G, Laschi R, Pileri S, Nishikawa S, Itoh Y, Seiki M, Itohara S, Takahashi C,
Rivano MT, Alampi G, Branzi A. Ultrastructural and Noda M. The membrane-anchored MMP inhibitor
immunohistochemical contribution to the histogenesis RECK is a key regulator of extracellular matrix integrity
of human cardiac myxoma. Ultrastruct Pathol. 1988; and angiogenesis. Cell. 2001;107:789–800.
12:221–33. 22. Dollery CM, McEwan JR, Henney AM. Matrix metal-
8. Landon G, Ordonez NG, Guarda LA. Cardiac myxo- loproteinases and cardiovascular disease. Circ Res.
mas. An immunohistochemical study using endothe- 1995;77:863–8.
lial, histiocytic, and smooth-muscle cell markers. 23. Singer CF, Kronsteiner N, Marton E, Kubista M,
Arch Pathol Lab Med. 1986;110:116–20. Cullen KJ, Hirtenlehner K, Seifert M, Kubista E.
9. Pucci A, Gagliardotto P, Zanini C, Pansini S, di Summa MMP-2 and MMP-9 expression in breast cancer-
M, Mollo F. Histopathologic and clinical characteriza- derived human fibroblasts is differentially regulated
tion of cardiac myxoma: review of 53 cases from a by stromal–epithelial interactions. Breast Cancer Res
single institution. Am Heart J. 2000;140:134–8. Treat. 2002;72:69–77.
10. McComb RD. Heterogeneous expression of factor 24. Markwald RR, Fitzharris TP, Manasek FJ. Structural
VIII/von Willebrand factor by cardiac myxoma cells. development of endocardial cushions. Am J Anat
Am J Surg Pathol. 1984;8:539–44. 1977;148:85–119.
25. Kodama H, Hirotani T, Suzuki Y, Ogawa S, Yamazaki 40. Stratakis CA, Carney JA, Lin JP, Papanicolaou DA,
K. Cardiomyogenic differentiation in cardiac myxoma Karl M, Kastner DL, Pras E, Chrousos GP. Carney
expressing lineage-specific transcription factors. Am complex, a familial multiple neoplasia and lentigino-
J Pathol. 2002;161:381–9. sis syndrome: analysis of 11 kindreds and linkage to
26. Schwartz RJ, Olson EN. Building the heart piece by the short arm of chromosome 2. J Clin Invest.
piece: modularity of cis-elements regulating Nkx2.5 1996;97:699–705.
transcription. Development. 1999;126:4187–92. 41. Dijkuizen T, van den Berg E, Molenaar WM, Meuzelaar
27. Riazi AM, Lee H, Hsu C, Van Arsdell G. CSX/Nkx2.5 JJ, de Jong B. Rearrangements involving 12p12 in two
modulates differentiation of skeletal myoblasts and cases of cardiac myxoma. Cancer Genet Cytogenet.
promotes differentiation into neuronal cells in vitro. 1995;82:161–2.
J Biol Chem. 2005;280:10716–20. 42. Kirscher LS, Carney JA, Pack SD, Taymans SE,
28. Sugi Y, Lough J. Onset of expression and regional Giatzakis C, Cho YS, Cho-Chung YS, Stratakis CA.
deposition of alpha-smooth and sarcomeric actin Mutations of the gene encoding the protein kinase A
during avian heart development. Dev Dyn. type I-alpha regulatory subunit in patients with the
1992;193:116–24. Carney complex. Nat Genet. 2000;26:89–92.
29. Valente M. Structural profile of cardiac myxoma. 43. Grebenc ML, Rosado-de-Christenson ML, Green CE,
Appl Pathol. 1983;1:251–63. Burke AP, Galvin JR. Cardiac myxoma: imaging fea-
30. Zhang PF, Jones JW, Anderson WR. Cardiac myxomas tures in 83 patients. Radiographics. 2002;22:673–89.
correlative study by light, transmission, and scanning 44. Curatolo P, Bombardieri R, Jozwiak S. Tuberous scle-
electron microscopy. Am J Cardiovasc Pathol. rosis. Lancet. 2008;372:57–668.
1989;2:295–300. 45. Wilkes D, Charitakis K, Basson CT. Inherited disposi-
31. Sugi Y, Markwald RR. Formation and early morpho- tion to cardiac myxoma development. Nat Rev Cancer.
genesis of endocardial endothelial precursor cells and 2006;6:157–65.
the role of endoderm. Dev Biol. 1996;175:66–83. 46. Lo Muzio L. Nevoid basal cell carcinoma syndrome
32. Gitler AD, Lu MM, Jiang YQ, Epstein JA, Gruber PJ. (Gorlin syndrome). Orphanet J Rare Dis. 2008;3:32.
Molecular markers of cardiac endocardial cushion 47. Callender GG, Rich TA, Perrier ND. Multiple endo-
development. Dev Dyn. 2003;228:643–50. crine neoplasia syndromes. Surg Clin North Am.
33. Nakajima Y, Mironov V, Yamagishi T, Nakamura H, 2008;88:863–95.
Markwald RR. Expression of smooth muscle 48. Vaughan CJ, Weremowicz S, Goldstein MM, Casey
alpha-actin in mesenchymal cells during formation of M, Hart M, Hahn RT, Devereux RB, Girardi L, Schoen
avian endocardial cushion tissue: a role for transform- FJ, Fletcher JA, Morton CC, Basson CT. A t(2;19)
ing growth factor beta3. Dev Dyn. 1997;209: (p13; p13.2) in a giant invasive cardiac lipoma from a
296–309. patient with multiple lipomatosis. Genes Chromosomes
34. Moorman A, Webb S, Brown NA, Lamers W, Cancer. 2000;28:133–7.
Anderson RH. Development of the heart: (1) forma- 49. Madueme P, Hinton R. Tuberous sclerosis and cardiac
tion of the cardiac chambers and arterial trunks. Heart. rhabdomyomas: a case report and review of the litera-
2003;89:806–14. ture. Congenit Heart Dis. 2011;6:183–7.
35. Noseda M, McLean G, Niessen K, Chang L, Pollet I, 50. Evans DG, Ladusans EJ, Rimmer S, Burnell LD,
Montpetit R, Shahidi R, Dorovini-Zis K, Li L, Thakker N, Farndon PA. Complications of the nae-
Beckstead B, Durand RE, Hoodless PA, Karsan A. void basal cell carcinoma syndrome: results of a pop-
Notch activation results in phenotypic and functional ulation based study. J Med Genet. 1993;30:460–4.
changes consistent with endothelial-to-mesenchymal 51. Gorlin RJ. Nevoid basal cell carcinoma (Gorlin) syn-
transformation. Circ Res. 2004;94:910–7. drome. Genet Med. 2004;6:530–9.
36. Akiyama H, Chaboissier MC, Behringer RR, Rowitch 52. Orlandi A, Ferlosio A, Roselli M, Chiariello L,
DH, Schedl A, Epstein JA, de Crombrugghe B. Spagnoli LG. Cardiac sarcomas: an update. J Thorac
Essential role of Sox9 in the pathway that controls Oncol. 2010;9:1483–9.
formation of cardiac valves and septa. Proc Natl Acad 53. Lymbumer R. Tumours of the heart: histopathological
Sci USA. 2004;101:6502–7. and clinical study. Can Med Assoc J. 1934;30:368–73.
37. Ranger AM, Grusby MJ, Hodge MR, Gravallese EM, 54. Burke A, Veinot J, Loire R. Tumours of the heart. In:
de la Brousse FC, Hoey T, Mickanin C, Baldwin HS, Travis W, Brambilla E, Müller H, Harris C, editors.
Glimcher LH. The transcription factor NF-ATc is Tumours of the lung, pleura, thymus and heart. Lyon:
essential for cardiac valve formation. Nature. IARC Press; 2004. p. 251–88.
1998;392:186–90. 55. Mazzola A, Spano JP, Valente M, Gregoriani R,
38. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go Villani C, Di Eusanio M, Ciocca M, Minuti U,
VL. The complex of myxomas, spotty pigmentation, Giancola R, Basso C, Thiene G. Leiomyosarcoma of
and endocrine overactivity. Medicine (Baltimore). the left atrium mimicking a left atrial myxoma.
1985;64:270–83. J Thorac Cardiovasc Surg. 2006;131:224–6.
39. Pinede L, Duhaut P, Loire R. Clinical presentation of 56. Basso C, Valente M, Poletti A, Casarotto D, Thiene G.
left atrial cardiac myxoma: a series of 112 consecutive Surgical pathology of primary cardiac and pericardial
cases. Medicine (Baltimore). 2001;80:159–72. tumors. Eur J Cardiothorac Surg. 1997;12:730–7.
57. Castorino F, Masiello P, Quattrocchi E, Di Benedetto 62. Hazelbag HM, Szuhai K, Tanke HJ, Rosenberg C,
G. Primary cardiac rhabdomyosarcoma of the left Hogendoorn PC. Primary synovial sarcoma of the
atrium: an unusual presentation. Tex Heart Inst J. heart: a cytogenetic and molecular genetic analysis
2000;27:206–8. combining RT-PCR and COBRA-FISH of a case
58. Cessna MH, Zhou H, Perkins SL, Tripp SR, Layfield with a complex karyotype. Mod Pathol. 2004;17:
L, Daines C, Coffin CM. Are myogenin and myoD1 1434–9.
expression specific for rhabdomyosarcoma? A study 63. Miller DV, Deb A, Edwards WD, Zehr KJ, Oliveira
of 150 cases, with emphasis on spindle cell mimics. AM. Primary synovial sarcoma of the mitral valve.
Am J Surg Pathol. 2001;25:1150–7. Cardiovasc Pathol. 2005;14:331–3.
59. Garcia JM, Gonzalez R, Silva JM, Dominguez G, 64. Mertens F, Fletcher CD, Antonescu CR, Coindre JM,
Vegazo IS, Gamallo C, Provencio M, España P, Bonilla Colecchia M, Domanski HA, Downs-Kelly E, Fisher
F. Mutational status of K-ras and TP53 genes in primary C, Goldblum JR, Guillou L, Reid R, Rosai J, Sciot R,
sarcomas of the heart. Br J Cancer. 2000;82:1183–5. Mandahl N, Panagopoulos I. Clinicopathologic and
60. Naka N, Tomita Y, Nakanishi H, Araki N, Hongyo molecular genetic characterization of low-grade
T, Ochi T, Aozasa K. Mutations of p53 tumor-sup- fibromyxoid sarcoma, and cloning of a novel FUS/
pressor gene in angiosarcoma. Int J Cancer. CREB3L1 fusion gene. Lab Invest. 2005;85:
1997;71:952–5. 408–15.
61. Amary MF, Berisha F, Bernardi Fdel C, Herbert A, 65. Jakowski JD, Wakely Jr PE. Primary intrathoracic
James M, Reis-Filho JS, Fisher C, Nicholson AG, low-grade fibromyxoid sarcoma. Hum Pathol.
Tirabosco R, Diss TC, Flanagan AM. Detection of 2008;39:623–8.
SS18-SSX fusion transcripts in formalin-fixed 66. Palmer JL, Masui S, Pritchard S, Kalousek DK,
paraffin-embedded neoplasms: analysis of conven- Sorensen PH. Cytogenetic and molecular genetic
tional RT-PCR, qRT-PCR and dual color FISH as analysis of a pediatric pleomorphic sarcoma reveals
diagnostic tools for synovial sarcoma. Mod Pathol. similarities to adult malignant fibrous histiocytoma.
2007;20:482–96. Cancer Genet Cytogenet. 1997;95:141–7.
Index
A Cardiac transplantation. See Transplantation

Adult cellular rhabdomyoma, 24, 55 Capillary hemangiomas, 48–49
Angioma. See Hemangioma Carcinosarcoma, 84
Angiosarcoma Cardiac catheterization, 132
chemotherapy, 167, 171–173 Cardiac lymphangiomas, 51
classification, 24, 73 Cardiac metastases, 23, 96, 112, 127, 145, 151–162, 190
clinical presentation, 74 clinical diagnosis, 161, 162
computed tomography (CT), 117 clinical manifestations, 151, 152
differential diagnosis, 40 echocardiography, 112, 113
echocardiography, 74, 75, 109, 113 endocardial involvement, 153, 154
epidemiology and localization, 26, 74 epicardial or myocardial metastatic involvement, 153
endomyocardial biopsy, 26, 75 epidemiology
grading, 25 frequency of metastases, 154
gross and histopathological features, 74, 75 location of metastases, 155
immunohistochemistry 189–190 malignant tumors, 154
MDCT 117 morphological aspects
MRI, 123, 124 endocardial metastases, 159–161
prognosis, 76 epicardial metastases, 157–159
radiotherapy 175 myocardial metastases, 159
surgical management, 142, 143 pericardial metastases, 156
systemic therapy (see Chemotherapy) pericardial involvement, 152
Anthracyclines, 171, 175–176 rates of, 151, 152
Anti-angiogenic therapy, 167 Cardiac myxoma. See Myxoma
Arterio-venous hemangioma, 48–50 Cardiac sarcomas, 24, 25, 73
Atrioventricular (AV) node, cystic tumor of, 24, 27, 29, genetic features, 190, 191
54–55, 142 immunohistochemical features, 190, 191
Autotransplantation 13, 74, 77, 134, 144, 145, 167, 169 Cardiac magnetic resonance imaging. See Magnetic
resonance
Classification of, 23, 24
B Cardiopulmonary bypass circuit, 66, 68, 96, 131, 133, 134
Bevacizumab, 172 Cardiotoxicity
Bioptic cardiac tumors, primary anthracyclines, 175–176
benign, 24, 26 ifosfamide, 176
malignant, 24, 26 taxanes, 176–177
Blood cyst, 53, 54 vascular endothelial growth factor blocking agents, 177
Bronchogenic cyst, intracardiac 56 Carney complex, 31–34, 41, 63, 188
Biopsy. See Endomyocardial biopsy Cavernous hemangiomas, 48, 49
Chemotherapy, 74, 77, 81, 83, 96, 144, 145, 153, 159,
165–179
C Cirsoid aneurysm. See Arterio-venous hemangioma
Carcinoma. See Cardiac metastases Columbus, M.R., 1, 131
Cardiac fibroma. See Fibroma Crafoord, C., 3, 133
DOI 10.1007/978-1-62703-143-1, © Springer Science+Business Media New York 2013
196 Index
Cardiac pheochromocytoma. See Paraganglioma Fibrosarcoma, 78, 79

Classification, cardiac tumors 23, 24 Focal lipid cardiomyopathy. See Histiocytoid
Computed tomography (CT), 3, 8, 13, 15, 48, 74, 113, cardiomyopathy
117, 128–132, 152, 175. See also Multi-
detector computerized tomography (MDCT)
Cystic tumor of atrioventricular node. See G
Atrioventricular node, cystic tumor of Gemcitabine, 164, 170–172
Genetics, cardiac tumors
angiosarcoma, 76
D cardiac sracomas, 190, 191
Docetaxel, 170, 171, 177 fibroma, 63, 188, 189
Doxorubicin (DOX), 164, 170–177 myxoma, 31, 33, 34, 188
paraganglioma, 188
rhabdomyoma, 60, 188
E rhabdomyosarcoma, 81
Echinococcus cysts, 16, 20 synovial sarcoma, 83
Echocardiography Germ cells tumors. See Intrapericardial teratoma
anecdotal case studies, 6, 8 Giant Lambl excrescence. See Papillary fibroelastoma
asymmetric hypertrophic cardiomyopathy, 13, 14 (PFE)
lipoma, 105 Glandular cardiac myxoma, 33, 36–38, 184
cardiac metastases, 112–113 Goldberg, H.P., 2
fibroma, 108 Gorlin (Goltz)syndrome, 63, 188, 189
hemangioma, 108, 109 Grading system, sarcomas 24, 25, 73
lipomatous hypertrophy, interatrial septum, 105
lymphoma, 110–112
malignant vs. benignant lesion, 92–95 H
metastatic tumors, 96–99 Hamartoma of mature cardiomyocytes, 24, 55
myxoma, 3, 4, 8, 9, 103–105 Hemangioma, 15, 18, 24, 26–28, 30, 48–51, 68,
papillary fibroelastoma, 105–107 94, 132, 142
rhabdomyomas, 107–108 echocardiography, 51, 94, 108, 109, 142
sarcoma, 109–110 histopathologic features, 48
teratoma, 108–109 immunohistochemistry, 50
transesophageal, 92, 95–97, 101–106, 109, 111, 113, Kasabach–Merritt vascular syndrome, 51
132, 133, 136, 140, 151, 173 Hematic cyst, 27, 29, 30
three-dimensional (3D) 101–104, 106, 109, 113, 132 Histiocytoid cardiomyopathy, 69
transthoracic 48, 49, 93–97, 101–113, 132, 173
Endocardial fibroelastic papilloma. See Papillary
fibroelastoma I
Endocardial metastases, 159–161 Idiopathic infantile cardiomyopathy. See Histiocytoid
Endomyocardial biopsy, 9, 13, 19, 75, 78 cardiomyopathy
Epidemiology, cardiac tumors, 23 Ifosfamide, 166, 170–172, 176
Epirubicin, 170 Inflammatory myofibroblastic tumor, 24, 55,
Epicardial metastases, 157–159 69, 70
Epithelioid hemangioendothelioma, 72, 76, 77 Inflammatory pseudotumor. See Inflammatory
myofibroblastic tumor
Intensity-modulated RT (IMRT), 173–175, 178
F International Classification of Diseases for Oncology
Fédération Nationale des Centre de Lutte Contre le (ICD-0), 24
Cancer (FNCLCC) system, 24, 25, 73 Intrapericardial teratoma. See Teratoma
Fibroma, 11, 13, 14, 15, 24, 26, 29, 30, 32, 62, 63, 64,
91, 92, 108, 113, 121–123, 132, 135, 139,
141, 188, 189 K
clinical symptoms, 62–64 Kaposi’s sarcoma, 84
echocardiography, 63, 92, 108 Kasabach–Merritt vascular syndrome, 51
epidemiology, 24–30
genetics, 188
gross examination, 62 L
histology, 63 Leiomyosarcoma, 24–26, 81–83, 92, 110, 124, 142,
magnetic resonance (MRI), 122, 123 165, 189, 190
surgical management, 135, 139, 141 Lepidic cells, 33, 35, 36, 38, 39
Index 197
Lipoma, 13, 24, 27, 29, 52, 69 P

echocardiography, 92, 94, 105 Paclitaxel, 167, 170, 171, 177
MRI, 118, 120, 121 Papillary fibroelastoma (PFE), 24, 28
surgical management, 131, 133, 138, 139 Paraganglioma (or cardiac pheochromocytoma),
Lipomatous hypertrophy., 29, 52, 53, 93, 105, 121, 56, 94, 142, 188
138, 139 Pediatric age , primary cardiac tumors, 8, 16, 27-31,
Liposarcoma, 24, 73, 83, 125, 142, 189 59-70, 121, 126, 188, 191
Lithomyxoma, 8, 11, 16, 35, 38 Pericardial cysts, 29, 55, 56
Loeffler fibroplastic endocarditis, 16, 19 Pericardial metastases, 156, 161, 162
Lymphoma,primary 10, 24, 26, 73, 84, 85, 165–167 PFE. See Papillary fibroelastoma (PFE)
echocardiography, 97, 98, 110–112, 166, 167 Plasma cell granuloma. See Inflammatory
MRI, 125, 126 myofibroblastic tumor
surgical management, 142, 143 Prenatal diagnosis, 11, 59, 62
Lymphoma, secondary 13, 111, 112, 127, 145, 155, Prichard, R., 1, 2
159, 160, 162 Primary cardiac lymphoma (PCL). See Lymphoma
PRKAR1A gene mutations, myxoma,
33, 34
M Purkinje cell tumor. See Histiocytoid cardiomyopathy
Magnetic resonance imaging (MRI), 3, 13, 15, 115–132
Mahaim, I., 1–3, 5, 6, 15
Malignant pleomorphic fibrous histiocytoma (MFH)/ R
undifferentiated sarcomas, 24–26, 40, 73, Radiation therapy (RT), 74, 77, 97, 166–169,
76–78, 84, 110, 123, 124, 142, 171, 189–191 172–179
Malignant mesenchymoma, 84 Radiotherapy. See Radiation therapy
Malignant mesothelioma, 24, 26, 73, 83, 85, 86, 127, Rhabdoid tumor, malignant, 84
129, 190 Rhabdomyoma, 11, 24, 27, 29, 30, 59–61,
Malignant peripheral nerve sheath tumor (MPNST), 84 132, 141, 188
Malignant schwannoma, 26, 73, 84 Rhabdomyosarcoma, 24, 73, 79–81, 110, 123,
Matrix metalloproteinases or metalloproteases (MMPs), 125, 142, 189, 190
32, 186
Multi-detector computerized tomography (MDCT).
See also Computed tomography S
advantages, 115 Sarcoma. See Cardiac sarcoma, Echocardiography
diagnostic accuracy, 126, 127 Secondary cardiac tumors. See Cardiac metastases
scanners, 116, 117 Solitary fibrous tumor, 85
Myocardial metastases, 159 Synovial sarcoma, 83
Myxoid (or fibromyxoid) sarcomas, 31, 39, 41, 79, 190
Myxosarcoma, 41, 73, 78–79
T
Tadpole cells, 81
N Target therapy, 167, 172, 173
Neurofibrosarcoma, 84 Tawarioma. See Atrioventricular (AV) node,
Non-neoplastic cardiac masses cystic tumor of
calcium, 16 Taxanes, 171, 176, 177
echinococcosis, 16, 20 Teratoma, 11, 15, 27, 29, 30, 59, 66–68, 93, 108,
histological examination, 15 131–133, 142
infections, 16, 20 Triton’s tumor, 84
loeffler endocarditis, 16, 19
thrombi, 15–17
V
Vascular endothelial growth factor (VEGF), 172
O
Oncocytic cardiomyopathy. See Histiocytoid
cardiomyopathy Y
Osteosarcomas, 40, 73, 78, 110, 124, 142 Yolk sac tumor, 66, 86, 87

Cardia Tumor Pathology

Uploaded by

Copyright:

Available Formats

Cardia Tumor Pathology

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Cardia Tumor Pathology

Uploaded by

Copyright:

Available Formats

Current Clinical Pathology

Antonio Giordano, MD, PhD

For further volumes:

ISBN 978-1-62703-142-4 ISBN 978-1-62703-143-1 (eBook)

Library of Congress Control Number: 2012950036

© Springer Science+Business Media New York 2013

Printed on acid-free paper

Humana Press is a brand of Springer

Cardiac tumors were once considered a nosographic entity of scanty interest

Padua, Italy Cristina Basso M.D., Ph.D.

The Editors are supported in their research by the Registry of Cardio-

1 Cardiac Tumors: From Autoptic Observations

11 Cardiac Metastases ....................................................................... 151

Index ....................................................................................................... 195

Luigi P. Badano, M.D. Cardiology, Department of Cardiac, Thoracic and

Ornella Milanesi, M.D. Pediatric Cardiology, Department of Pediatrics,

Gaetano Thiene, Marialuisa Valente,

C. Basso et al. (eds.), Cardiac Tumor Pathology, Current Clinical Pathology, 1

Fig. 1.1 Portrait of

Fig. 1.4 Diagram

Medical School and the thaumaturgical power of

mimic valve papillary fibroelastoma. Valvular

19. Stritoni P, Daliento L, Fasoli G, Schivazappa L, Chioin

advent of cardiac surgery, it became a referral

C. Basso et al. (eds.), Cardiac Tumor Pathology, Current Clinical Pathology, 23

Table 2.1 Histological classification of tumors of the

(see for instance rhabdomyoma) or tumor resect-

In the time interval 1970–2010, 267 primary cardiac

Cystic tumor of the atrioventricular node

Fig. 2.6 Cardiac myxoma, University of Padua Medical

relapse following incomplete surgical resection,

C. Basso et al. (eds.), Cardiac Tumor Pathology, Current Clinical Pathology, 31

cutaneous myxoma, and blue naevi) [10] syn-

non-familial myxomas do not show mutations

Fig. 3.3 (continued)

(80–90%), attached to the endocardium, more

C. Basso et al. (eds.), Cardiac Tumor Pathology, Current Clinical Pathology, 45

hemangiomas are discovered incidentally at through echocardiography and MRI, and of

It is a primary benign cardiac tumor composed

15. McFadden PM, Lacy JR. Intracardiac papillary

of cardiac tumor was possible in 67 children among

C. Basso et al. (eds.), Cardiac Tumor Pathology, Current Clinical Pathology, 59

are mild or even absent, clinical follow-up, associ- Fibroma

clinically silent as to be an incidental finding dur-

There are a few differences in this recent

C. Basso et al. (eds.), Cardiac Tumor Pathology, Current Clinical Pathology, 73

pleomorphic sarcoma, undifferentiated sarcoma Imaging. Two-dimensional echocardiography

Genetic studies on angiosarcoma are extremely

is complete and tumor recurrence in the (endothelial, cardiomyocytes, smooth muscle

Fig. 6.4 Rhabdomyosarcoma in

Fig. 6.4 (continued)

Fig. 6.4 (continued)

alveolar, and pleomorphic. Primary cardiac rhab- Leiomyosarcoma

Treatment. Surgical resection is often palliative Histopathological features. Leiomyosarcoma con-

in the pleomorphic subtype presents with centrally

Primary Malignant Tumors of the Malignant mesothelioma. Primary pericardial

ence, which is particularly true for small and

C. Basso et al. (eds.), Cardiac Tumor Pathology, Current Clinical Pathology, 91

How to Distinguish a Malignant from

The histological differentiation of cardiac masses