2. CONTENTS
Introduction
History
PEComa family
Epidemiology
Etiology
Clinical features
Macroscopic findings
Microscopic findings and Classification
Electron microscopic findings
FISH, PCR, DNA sequencing, Genetic findings
Differential Diagnosis
Management and follow up
3. INTRODUCTION
Perivascular epithelioid cell tumors (PEComas) are
rare mesenchymal neoplasm with distinctive
morphology and immunohistochemical
characteristics.
They most often arise in the retro peritoneum,
visceral organs and abdomino-pelvic sites.
These tumors usually show reactivity for
melanocytic and smooth muscle markers
HMB45, Melan-A, MiTF, smooth muscle actin
(SMA) and calponin.
4. HISTORY
In 1992, Bonetti et al., firstly created the term of
perivascular epithelioid cell (PEC) to portray some
epithelioid type cells with a perivascular distribution
and immunoreactive for melanocyte markers.
In 2002, the World Health Organization took the
definition of “mesenchymal tumors composed of
histologically and immunohistochemically distinctive
perivascular epithelioid cells” as perivascular
epithelioid cell tumors (PEComas).
5. PECOMA FAMILY
Includes
1. Angiomyolipoma (AML)
2. Clear cell “sugar” tumor of the lung (CCST)
3. Lymphangioleiomyomatosis (LAM)
4. Clear cell myomelanocytic tumor of the falciform
ligament/ligamentum teres (CCMMT)
5. Unusual clear cell tumors in other locations
(uterus, colon, and soft tissues) (NOS)
6. Gastrointestinal tract (GI) is one of the most
common anatomic sites of origin and counts for
20% to 25% of all reported cases of perivascular
epithelioid cell tumors not otherwise specified
(PEComas-NOS).
PEComas have been reported in various anatomic
sites with a marked female predominance.
7. EPIDEMIOLOGY
Rare tumor. There are about 50 cases of GI PEComas-
NOS according to the literatures so far.
GI is the second most frequent site of PEComas, only
behind gynecological tract.
The age of patients who were diagnosed with GI
PEComas-NOS ranging from 5.5 to 97 years with an
average age of 38.9.
The most frequently involved location is colon.
Strong association with Tuberous sclerosis is seen.
8. PECOMA AND TUBEROUS SCLEROSIS
PEComas are related to the tuberous sclerosis complex (TSC)
or to the genetic alterations of TSC.
TS is an autosomal dominant genetic disease due to losses of
TSC1 (9q34) or TSC2 (16p13.3) genes
Characterized by:
- Mental retardation
- Seizures
- Cellular proliferations (AMLs, subependymal giant cell tumours,
cutaneous angiofibroma's, cardiac rhabdomyomas,
micronodular hyperplasia, lymphangioleiomyomatosis,
pulmonary multifocal micronodular hyperplasia)
10. ETIOLOGY
The exact cause of GI PEComas-NOS is not clear.
Theories:
1. Originate from PEC but the natural histological
counterpart is out of clarity.
2. From neural crest for their expressing many
melanocytic and muscular markers and as they are
ubiquitous.
3. From smooth muscle with possible molecular alteration
that brings to expression of melanogenesis and
melanocytic markers.
4. From telocyte as markers described in telocytes
(CD34, S-100, smooth muscle actin, and vascular
endothelial growth factor) are positive.
11. CLINICAL FEATURES
GI PEComa-NOS presents with non-specific
clinical signs.
With symptoms relying on the different organ
involved, the size of neoplasm and tumor volume,
principal clinical presentations.
Abdominal pain, melaena, rectal bleeding,
obstruction, weight loss, anemia, and some even
asymptomatic.
Abdominal pain is most frequent (35%) that may
result from oppression, impaction, and hemorrhage.
12. LOCATISATION
PEComas of the digestive tract frequently arise
from colon, liver, small intestine, pancreas.
Also seen in mesentery and peritoneum
Very rare in stomach
Angiomyolipoma is a subtype that contains adipose
tissue and tortuous and thick walled vessels almost
exclusively is present in liver, kidney and pancreas.
13. ENDOSCOPY
Endoscopy can help to detect the lesion, which includes
polypoid tumor or fungating mass protruding into the lumen with
ulcerated or smooth surface.
14. MACROSCOPIC FINDINGS
Always well circumscribed and no capsule
formation, while some can show ill-defined border
or infiltrative growth.
Solid or soft polypoid lesion locating in the mucosa
or submucosa.
The neoplasm also can be a round or ovoid mass
which originates from any layer and even invades
the wall.
The cut surface color varies from grayish-white,
dark red, or pinkish-grey with a central ulcer,
hemorrhage and necrosis.
16. MICROSCOPIC FINIDNGS
Arrangement: Biphasic pattern in sheets or nests
surrounded by thin walled capillaries.
Spindle cell component: Resembles smooth muscle away
from vessels, arranged in fascicular pattern with rich
vascularity. Individual cell is slightly eosinophilic with granular
cytoplasm, oval nuclei and small distinct nucleoli.
Epithelioid component: The cytoplasm of epithelioid cell is
usually clear to pale eosinophilic. The nuclei are oval to
polygonal and the nucleoli is prominent and centrally located.
GI PEComa-NOS shows epithelioid predominance (70%).
Perivascular cells are nearly all epithelioid.
17. SCELROSING PEComa: About 15% of cells are
present in cords in a densely collagenous stroma.
Focal association with blood vessel wall with radial
arrangement of tumor cells and subendothelial
growth is a typical feature.
Typical Pecomas may contain occasional
multinucleate cells, show limited pleomorphism and
very scarce mitotic activity.
18. Microscopic features of the ileum tumor: The tumor consisted of an
epithelioid cell proliferation with a vaguely nested pattern (A). In some
areas, the tumor displayed a pseudoglandular histological appearance
(B). The perivascular epithelioid cells had clear to eosinophilic granular
cytoplasm with some slightly irregular nucleus nuclei (C). Foci of
coagulation necrosis were also found in the tumor (D).
19. MALIGNANT PECOMA OF STOMACH
A: Gross showing a large
tumor attached to the lesser
curvature of stomach.
B: Sheets or nests of markedly
atypical epithelioid cells having
hyperchromatic pleomorphic
nuclei and abundant
eosinophilic to clear cytoplasm,
admixed with a large number
of multi-nucleated giant cells
(inset), supported by delicate
fibrovascular septa.
C: Radial perivascular fashion
With atypical mitosis.
D: Vascular permeation of the
infiltrative tumor nests
20. ELECTRON MICROSCOPY
Cells contain abundant glycogen, melanosomes,
premalanosomes, thin filaments and occasional dense bodies,
hemidesmosomes and poorly formed intercellular junctions.
21. MALIGNANT TRANSFORMATION
The 2002 WHO Soft Tissue and Bone book wrote:
PEComas displaying any combination of
Infiltrative growth
Marked hypercellularity
Nuclear enlargement
Hyperchromasia
High mitotic activity
Atypical mitotic figures
Coagulative necrosis
should be regarded as malignant.
23. IMMUNOHISTOCHEMISTRY
HMB-45: Most sensitive
Melan-A: Second most sensitive
TFE3 : Potential role in the acquisition of the
distinct histopathologic appearance
MiTF
SMA
S100
Desmin
CD117
CD34
Cytokeratin
25. FISH, PCR AND DNA SEQUENCING
Rearrangement of TFE3
Gene fusions:
1. SFPQ/ PSF-TFE3
2. PSF-TFE3
3. PRCC-TFE3
4. EWS-ATF1
Up regulation of MiTF, TYR, CDK2, TBX2, and C-
MET.
26. TFE3 GENE
TFE3 gene encodes a transcription factor
• TFE3 gene, located on Xp11.2, is translocated with a number of partner
genes, commonly in MiT family.
• Translocation often leads to overactivation of TFE3 and subsequent cell
proliferation and oncogenesis.
• Translocation seen in
1. Renal cell carcinoma
2. Alveolar soft part sarcoma
3. Epithelioid hemangioendotheliomas
4. Perivascular epitheloid cell tumors (PEComas)
5. Solid pseudopapillary neoplasms of the pancreas
6. Ovarian sclerosing stromal tumor
27. GENETICS
Multiple
chromosomal
imbalances with
16p loss
X-chromosomal
gains
mTOR pathway
activation.
(Receptor tyrosine
kinase, phosphoinositide
3-kinase, Protein kinase
B(AKT), mammalian
target of Rapamycin
complex)
28. PROGNOSIS
PEComas with marked nuclear atypia, diffuse
pleomorphism, mitotic activity (>1 mitosis/mm2)
have strongest risk factor for malignancy.
Borderline tumors need regular follow-up.
29. DIFFERENTIAL DIAGNOSIS
1. GIST
PEComas and GIST show eosinophilic or clear
cytoplasm but PEComa is different form GIST for its
distinct perivascular concentric proliferation and
representative granular cytoplasm.
HMB-45 and Melan A are the most helpful tool for
PEComas.
30. 2. MALIGNANT MELANOMA:
Cells in malignant melanoma are various in shape such
as epithelioid, spindle, small round, signet ring or
plasmacytoid. The clinical history of primary tumor of
skin is regarded as the most basic element for
differential diagnosis.
S100 is positive in myeloma and negative in PEComa.
31. 3. SMOOTH MUSCLE TUMOR:
Smooth muscle tumor shows disseminate cytoplasmic
eosinophilia, vacuoles around the nucleus, and “cigar-
shaped” nuclei while PEComa manifests clear to lightly
eosinophilic cytoplasm, and round or ovoid nuclei.
HMB-45 and Melan-A are negative in smooth muscle
tumor.
Multinucleated giant cells promote diagnosis of
PEComas
32. 4. RENAL CELL CARCINOMA:
Chromophobe cell type has epithelioid appearance and
rich angiogenesis.
History of primary renal tumor is straightforward.
The positive for CK, CD117, CD10, RCC antigen
33. 5. PARAGANGLIOMA:
Has organoid growth pattern
Has diffuse synaptophysin and chromogranin positivity
marker but negative for myoid and melanocytic markers.
34. 6. GI CLEAR CELL SARCOMA
Always has nests of round or epithelioid cells and mixed
osteoclast-like giant cells.
It expresses S100 strongly.
35. 7. CARCINOMA (adrenocortical or hepatocellular
carcinoma):
The expression of melanocytic markers (HMB-45 and
Melan-A)
Lack of immunoreactivity for cytokeratins help to
exclude the diagnosis of carcinoma
36. MANAGEMENT AND FOLLOW UP
Surgical resection is the most important and common
method for primary tumor or local recurrence of GI
PEComas.
Chemotherapy and imunotherapy with IFN is given in
malignant cases.
The longest period of follow-up in the articles was 180
months.
The patient who had radical excision with a favorable
outcome
Physical examination and CT scans every 6 months and
yearly endoscope was also recommended.
38. OTHER ORGANS INVOLVED IN
PECOMA- LUNG
Clear cell PEComa:
(A) Core needle biopsy shows neoplastic cells in nested and
insular pattern surrounding numerous thinned wall sinusoid-like
vessels
(B) intranuclear cytoplasmic invaginations
(C) HMB45+ staining
39. OTHER ORGANS INVOLVED IN
PECOMA- LUNG
Lymphangioleiomyomatosis:
• Thin walled cystic air spaces and patchy, disordered, clustered to
nodular proliferation of bland spindled and cuboidal epithelioid cells
around airways, lymphatics, blood vessels
•Spindle cells are located centrally with peripheral epithelioid cells
42. REFRENCES
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Rosai, J., Ackerman, L. V., & Rosai, J. (2011). Rosai and Ackerman's
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Classification of Tumours, 4th Edition, Volume 5, Edited by Fletcher
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