Annals of
DIAGNOSTIC
PATHOLOGY
VOL 4, NO 6
DECEMBER 2000
ORIGINAL ARTICLES
Salivary Gland Tumors of the Mandible
Fernando Martı́nez-Madrigal, MD, Keyla Pineda-Daboin, MD, Odele Casiraghi, MD,
and Mario A. Luna, MD
Primary central salivary gland carcinomas of the mandible are uncommon neoplasms. Consequently, their proper diagnosis is often in doubt. We retrospectively
studied the cases of 16 patients treated at The University of Texas M. D. Anderson
Cancer Center and the Institut Gustave Roussy from 1950 to 1990. Patients ranged
in age from 24 to 76 years (mean, 51 years). Nine patients were women and seven
were men. Each case involved either the angle or the posterior body of the mandible.
Swelling, pain, and trismus were the most frequent complaints. For all patients,
radiography revealed a cystic defect resembling an osteolytic odontogenic lesion or
metastasis. Five histologic types of carcinoma were diagnosed: seven cases of
mucoepidermoid carcinoma (five low-grade and two high-grade), four cases of
adenoid cystic carcinoma, two cases of adenocarcinoma, two cases of acinic-cell
carcinoma, and one case of epithelial-myoepithelial carcinoma. All patients were
treated with wide surgical excision. Eight patients received postoperative irradiation. Five patients with low-grade mucoepidermoid carcinoma, two with acinic-cell
carcinoma, and one with epithelial-myoepithelial carcinoma were free of disease 2 to
15 years after initial treatment (mean, 6.2 years). Two patients with adenoid cystic
carcinoma are living with lung metastasis. The remaining six patients died of their
carcinomas within 4 years after initial treatment. Because of their unique morphology and clinical behavior, these tumors should be distinguished from other intraosseous neoplasms of the mandible, including those with clear-cell patterns.
Ann Diagn Pathol 4: 347-353, 2000. Copyright © 2000 by W.B. Saunders Company
Index Words: Salivary gland neoplasms, mandible, mucoepidermoid carcinoma,
adenoid cystic carcinoma, acinic-cell carcinoma, epithelial-myoepithelial carcinoma
E
CTOPIC salivary gland tissue has been reported in a wide variety of locations, including
the thyroid, the pituitary, the middle ear, the maxilla, and the mandible.1-3 Neoplastic transformation of heterotopic salivary tissue is rare, and most
From the Department of Pathology, Instituto de Investigaciones Biomédicas de Michoacán, Morelia, Michoacan, México; the Department of
Pathology, The University of Texas M. D. Anderson Cancer Center,
Houston, TX; and the Department of Pathology A, Institut Gustave
Roussy, Villejuif, France.
Address reprint requests to Mario A. Luna, MD, Department of
Pathology, The University of Texas M. D. Anderson Cancer Center,
1515 Holcombe Blvd, Box 85, Houston, TX 77030.
Copyright © 2000 by W.B. Saunders Company
1092-9134/00/0406-0004$10.00/0
doi:10.1053/adpa.2000.19395
reported cases are in the upper cervical lymph
nodes and in the mandible.1 When neoplastic
transformation occurs centrally within the mandible, the radiologic and clinical presentation may
mimic that of odontogenic tumors, and a final
diagnosis can be obtained only after histologic examination.4 Careful gross and microscopic examination of the surgical specimen should be done to
exclude the possibility of any connection with the
mucosal cover of the oral cavity. Mucoepidermoid
carcinomas are the most frequently reported types
of primary central salivary gland carcinomas of the
mandible.4,5 Much less common are adenoid cystic
carcinomas, adenocarcinomas, and acinic-cell carcinomas.6-15 Recently, two cases of hyalinizing clearcell carcinomas of the mandible were reported.9
Annals of Diagnostic Pathology, Vol 4, No 6 (December), 2000: pp 347-353
347
348
Martı́nez-Madrigal et al
This retrospective study describes 16 patients
with primary salivary gland carcinomas arising centrally within the mandible treated at the University
of Texas M. D. Anderson Cancer Center (Houston,
TX) and the Institut Gustave Roussy (Villejuif,
France). The clinicopathologic features of these
carcinomas are analyzed, and the probable histogenesis of salivary gland neoplasms arising centrally
within the mandible is briefly discussed.
Material and Methods
The files of the Departments of Pathology and
Head and Neck Surgery of M. D. Anderson Cancer
Center and the Institut Gustave Roussy were searched
for cases of primary central salivary gland carcinoma
of the mandible. The clinical data, radiographs, histologic material, surgical records, and follow-up information were analyzed. All cases met the following
criteria: radiographic evidence of bone destruction,
presence of an intact cortical plate, histologic confirmation of salivary gland neoplasm, absence of any
primary lesion in the salivary glands, exclusion of
odontogenic tumor, and absence of any connection
between the tumor and the mucosal surface as determined by analysis of serial sections of the tumor
specimen. The three specimens that had clear-cell
patterns (cases 14, 15, and 16) were stained with the
periodic acid-Schiff reagent with and without diastase
digestion and Alcian blue. Immunohistochemical
studies of these three specimens were performed.
Results
Fifteen patients treated at M. D. Anderson Cancer Center and five patients treated at the Institut
Gustave Roussy between 1950 and 1990 were
found. Four patients of the Institut Gustave Roussy
were excluded from the study because they had
evidence of connection between the intramandibular tumor and the oral mucosal surface.
The 16 study patients ranged in age from 24 to 76
years (mean, 51 years). Nine patients were women
and seven were men. Each case involved the angle or
the posterior body of the mandible (Table 1). Pain,
swelling, and trismus were the most frequent complaints. All patients showed radiographic evidence of
bone destruction and an intact cortical plate (Fig 1).
Gross examination of the specimens revealed multilocular intraosseous lesions (Fig 2).
Histologic and clinical data for all patients are
summarized in Table 1. Histologically, the types of
carcinomas were as follows: seven patients had mucoepidermoid carcinoma (Fig 3), four had adenoid
cystic carcinoma (Fig 4), two had adenocarcinoma,
two had acinic-cell carcinoma (Fig 5), and one had
epithelial myoepithelial carcinoma (Figs 6, 7) similar
to conventional salivary gland tumors. Acinic-cell carcinoma presented as a clear-cell tumor: periodic acidSchiff reaction and periodic acid-Schiff diastase digestive reaction were strongly positive, as was amylase
reaction by immunohistochemistry.
Table 1. Features, Treatment, and Follow-up of Sixteen Patients With Salivary Gland Tumors of the Mandible
Case
Age (yr)/
Sex
Site in
Mandible
Type
Treatment
Status
Follow-up
(yr)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
49/F
53/M
56/M
65/M
58/F
71/F
51/M
51/M
48/M
24/F
35/F
33/F
24/F
48/F
76/M
56/F
Body
Angle
Body
Angle
Angle
Angle
Body
Angle
Body
Angle
Angle
Body
Angle
Angle
Body
Angle
MEC-LG
MEC-LG
MEC-LG
MEC-LG
MEC-LG
MEC-HG
MEC-HG
ADC
ADC
ADC
ADC
AD
AD
ACC
ACC
EMC
MM
MM
MM
MM
MM
HM ⫹ XRT
HM ⫹ XRT
HM ⫹ XRT
HM ⫹ XRT
HM ⫹ XRT
HM ⫹ XRT
HM ⫹ XRT
HM ⫹ XRT
MM ⫹ XRT
MM ⫹ XRT
HM
NED
NED
NED
NED
NED
DOD
DOD
DOD
DOD
LWD
LWD
DOD
DOD
NED
NED
NED
15
8
6
7
10
3
2
4
3
7
5
4
3
12
2
8
Abbreviations: MED, mucoepidermoid carcinoma; LG, low-grade; HG, high-grade; ADC, adenoid cystic carcinoma; AD, adenocarcinoma; ACC, acinic-cell carcinoma; EMC, epithelial-myoepithelial carcinoma; MM, marginal mandibulectomy; HM, hemimandibulectomy; XRT, radiotherapy; NED, no evidence of disease; DOD, died of disease; LWD, living with disease.
Salivary Gland Tumors of the Mandible
349
Figure 1. Isolated portion of a Panorex radiograph showing a lytic lesion
with irregular margins in the left body
and ramus of the mandible.
All patients were treated by wide surgical excision.
Eight patients received postoperative irradiation.
Five patients with low-grade mucoepidermoid
carcinoma, two patients with acinic-cell carcinoma,
and one patient with epithelial-myoepithelial carcinoma were disease-free from 2 to 15 years after
initial treatment (mean, 6.2 years). Two patients
with adenoid cystic carcinoma are alive with lung
metastasis. The remaining six patients died of their
carcinomas within 4 years after initial treatment.
Discussion
Our study of 16 patients with salivary gland carcinomas of the mandible demonstrates the clinicopathologic features that distinguish these tumors from
other cancer types. Salivary gland carcinomas located
centrally within the mandible are rare, comprising
less than 0.4% of all salivary gland carcinomas. In a
study of 426 minor salivary gland tumors from 11
institutions, Waldron et al16 noted only six (1.4%)
intraosseous mucoepidermoid carcinomas. Brookstone and Huvos4 found only six cases (0.37%) of
salivary gland carcinoma of the mandible among
2,000 patients with sialocarcinomas registered from
1950 to 1990 in the Tumor Registry at the Memorial
Sloan-Kettering Cancer Center in New York. We
found 16 patients among 5,400 (0.29%) patients
treated during the same period for salivary gland
carcinomas at The University of Texas M. D. Anderson Cancer Center in Houston, Texas, and the Institut Gustave Roussy in Villejuif, France.
Specific criteria have been established for con-
Figure 2. Bisected gross specimen
showing a multilocular tumor.
350
Martı́nez-Madrigal et al
Figure 3. (Left) Intraosseous low-grade mucoepidermoid carcinoma of mandible. (Hematoxylin-eosin, magnification ⫻40.) (Right)
Hematoxylin-eosin. (Magnification ⫻100.)
firming the central origin of salivary gland tumors
involving the mandible4,5: (1) absence of any connection between the oral mucosal surface and the
lesion in the mandible or maxilla (because malignant carcinomas that develop in minor salivary
glands may infiltrate the bone by direct extension),
(2) radiographic evidence of bone destruction, (3)
presence of an intact cortical plate, (4) histologic
confirmation of salivary gland neoplasm, (5) absence of any primary lesions within the salivary
glands, and (6) exclusion of the diagnosis of odontogenic carcinoma.
The origin of salivary gland tumor tissue within
the jawbone is presumed to be a maternal salivary
gland. Salivary gland inclusions usually occur in
bone spaces located near the angle of the mandible, where they have a consistent position and
radiographic appearance.2 Only a few salivary
gland inclusions have been found in the anterior
mandible (in the incisor region or between the
canines and first molars).2
As several investigators have stated, no single
theory of histogenesis is applicable to all cases of
salivary gland tumors of the mandible.4,5,7,17 True
cases of central pleomorphic or monomorphic adenoma and adenoid cystic carcinoma do not arise
from a metaplasia of odontogenic cysts5,6 and must
therefore originate from (1) enclaved retromolar
Figure 4. Characteristic cylindromatous structures in an intramandibular
adenoid cystic carcinoma. (Hematoxylin-eosin, magnification ⫻40.)
Salivary Gland Tumors of the Mandible
351
Figure 5. Acinic-cell carcinoma with
alternating groups of clear and granular
cells. (Hematoxylin-eosin, magnification ⫻40.)
mucous glands during embryological development
of the jawbones, (2) submandibular and sublingual
glands closely apposed in bony defects or cavities in
the lingual cortex of the mandible, or (3) fragments of submandibular and sublingual glands that
have undergone embryologic evagination. Another
speculative source also has been proposed for the
origin of central mucoepidermoid carcinomas:
metaplasia in an odontogenic cyst or in the epithelial rests of Malassez.5,17,18 Two of seven patients
with mucoepidermoid carcinoma in the present series had odontogenic cysts, supporting the theory of
neoplastic or metaplastic cellular transformation.
The radiographic appearance of central salivary
gland tumors of the mandible often resembles that
of an osteolytic odontogenic lesion. However, several characteristics of the radiographic appearance
may help to verify the histopathologic type of central carcinoma of the mandible. In a series of 36
cases of central carcinomas of the jaws reported by
Chiang and Chih, most lesions with osteolytic destruction were primary intraosseous carcinomas,
most lesions with multilocular destruction were
salivary gland carcinomas, and most lesions with
unilocular destruction were malignant changes in
odontogenic cysts.19
The histology of central salivary gland neoplasms
in the mandible is identical to that of their salivary
Figure 6. Intramandibular epithelialmyoepithelial carcinoma. (Hematoxylin-eosin, magnification ⫻40.)
352
Martı́nez-Madrigal et al
Figure 7. Epithelial-myoepithelial carcinoma demonstrating clear-cell pattern surrounding ductal structures. (Hematoxylin-eosin, magnification ⫻100.)
gland counterparts and usually does not pose diagnostic difficulties. The principal differential diagnosis for mucoepidermoid carcinomas is metastasis
from other primary carcinomas and cystic odontogenic lesions, especially the sialodontogenic cyst,
also called the glandular odontogenic cyst.18,20,21
The presence of intermediate cells and multilocular destruction would favor the diagnosis of mucoepidermoid carcinoma.21 In the case of salivary
glands with predominantly clear-cell components
(epithelial-myoepithelial carcinoma, hyalinizing
clear-cell carcinoma, and acinic-cell carcinoma),22
the differential diagnosis of clear-cell odontogenic
tumors (clear-cell odontogenic carcinoma and
clear-cell calcifying epithelial odontogenic tumor)
is the most difficult.23-28 All of these odontogenic
neoplasms will show odontogenic epithelium if
enough histologic sections are examined.23-28 Metastatic renal-cell carcinoma should always be considered in the differential diagnosis of clear-cell
tumors.23 Metastatic melanoma and thyroid carcinoma may sometimes have a clear-cell appearance.
Immunohistochemical stains are useful in diagnosing these two carcinomas.23
Central mucoepidermoid carcinoma and adenoid cystic carcinoma are the only salivary gland
tumors with documentation sufficient to allow clinicopathologic analysis.4-6,17 Other salivary gland
carcinomas are presented in single case reports or
in small series with insufficient documentation.
Brookstone and Huvos4 indicated that only six
(9%) of 66 patients with central mucoepidermoid
carcinomas with adequate follow-up had evidence
of metastatic disease, whereas eight (50%) of 16
patients with central adenoid cystic carcinoma had
metastases. In a series of 66 patients with central
mucoepidermoid carcinomas reported by Waldron
and Koh,17 the metastatic rate was 12% (eight
patients), the recurrence rate was 26% (17 patients), and the mortality rate was only 9% (six
patients). In the present series, two deaths (29%)
occurred among patients with mucoepidermoid
carcinoma; both patients had high-grade carcinoma. In contrast, of four patients with adenoid
cystic carcinoma, two died of carcinoma and two
are alive with tumor. The insidious clinical course
that characterizes adenoid cystic carcinoma may be
due to the tumor’s propensity to infiltrate nerves,
perineural spaces, and tissue planes.
Surgery is the predominant treatment modality for
central salivary gland tumors of the mandible.4-7 Surgical treatment has ranged from enucleation or curettage to en bloc or radical excision. Several patients
have also received radiotherapy.17 Enucleation with
or without electrocoagulation is associated with the
highest rate of recurrence (45%), but no method of
treatment completely eliminates the potential for recurrence. As recorded in the review by Waldron and
Koh,17 rates of metastasis and mortality were highest
in patients who had received hemimaxillectomy or
hemimandibulectomy. However, this finding likely
reflects an advanced stage of disease at the time of
initial treatment.
The treatment approach in the 16 cases described
was as follows. Small tumors were treated with marginal mandibulectomy. If tumor histology in these
Salivary Gland Tumors of the Mandible
cases indicated high-grade disease, radiotherapy was
given postoperatively. Large tumors were treated with
mandibulectomy. If the carcinoma was of a high
histologic grade, if perineural invasion was present, or
if the tumor had invaded soft tissues, radiotherapy
was administered postoperatively. Neck dissection was
performed only when metastasis in the cervical lymph
nodes was suspected.
Brookstone and Huvos4 have emphasized that
without the help of clinical staging, any recommendations for treatment are of limited value. The investigators propose a staging system for salivary gland
tumors within the mandible. Lesions that are located
within undisturbed, intact cortical bone and overlying
periosteum and that show no signs of cortical expansion offer the best prognosis and therefore indicate
stage I disease. Stage II disease is characterized by
lesions surrounded by intact cortical bone that has
undergone some degree of expansion. An instance of
cortical perforation, breakdown of the overlying periosteum, or nodal metastatic spread is categorized as
stage III disease. Logically, a 6-cm mucoepidermoid
carcinoma confined to an otherwise undisturbed
mandible offers a more favorable prognosis than a
1-cm mucoepidermoid carcinoma that aggressively
invades the floor of the mouth following lingual
expansion and perforation of the cortical bone. Our
findings support this staging system.
Although salivary gland tumors arising within the
mandible are uncommon, their importance should
not be minimized. Because of their unique morphology and clinical behavior, these neoplasms should be
distinguished from other intraosseous tumors of the
mandible. Proper diagnosis depends on a thorough
physical examination, including a complete patient
medical history, radiographs, and a biopsy.
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