Osteoclastlike giant cell tumor of the salivary gland
Xueping Fang, MDa,⁎, David G. Hicks, MDb, Wesley Hicks Jr., MDc, Shaozeng Zhang, MDb
aDepartment of Pathology, SUNY at Buffalo, Buffalo General Hospital, Buffalo, NY 14203, USA
bDepartment of Surgical Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
cDepartment of Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
AbstractGiant cell tumor of the salivary gland is extremely rare, with only 15 cases published in the English
literature. The tumor characteristically contains a mixture of multinucleated giant cells, resembling
osteoclasts of bone, and neoplastic mononuclear cells. In about half of the reported cases, there is an
associated carcinomatous component. We are reporting an additional case of giant cell tumor of the
parotid gland that was initially misinterpreted as an extraosseous osteosarcoma in the biopsy
specimen. The histologic and immunohistochemical findings as well as a review of the literature with
discussion of the histogenesis of this unusual neoplasm are presented.
© 2009 Elsevier Inc. All rights reserved.
Keywords: Giant cell tumor; Salivary gland tumor; Parotid gland tumor; Osteoclast; Osteosarcoma; Carcinoma
Giant cell tumor (GCT) of the salivary gland is extremely
rare. It is typically composed of a mixed population of
multinucleated giant cells and mononuclear cells (MNCs).
The multinucleated giant cells morphologically resemble
those seen in GCTs of bone, therefore referred to as
osteoclastlike or osteoclast-type giant cells (OGCs). The
tumor sometimes also contains a variable amount of
carcinomatous components, including carcinoma ex pleo-
morphic adenoma and salivary duct carcinoma. In contrast to
GCT of bone, in which the nuclei of giant cells and
mononuclear cells are essentially similar to each other, the
nuclei of those 2 components are morphologically different
in salivary gland GCT. Since the first 3 cases of GCT of the
salivary gland were reported by Eusebi et al  in 1984,
12 additional cases have been added to the English literature
[2-9]. We are reporting the 16th case of such a tumor, with a
literature review and discussion of histogenesis and
2. Case report
The patient is a 43-year-old man who noted a mass in
the left lateral aspect of his face with rapid growth and fluid
drainage. The patient also complained of left facial
paralysis manifested by incomplete closure of the left eye
and inability to move his left facial muscle. On physical
examination, a firm mobile mass was palpated in the left
parotid region. Computer tomography showed a large
complex tumor in the same location. An open biopsy was
performed, and an extraosseous osteosarcoma was entered
into the differential diagnoses by the local pathologist.
Three months later, a total parotidectomy with facial nerve
sacrifice and parapharyngeal space resection of the tumor
was performed in Roswell Park Cancer Institute, Buffalo,
NY. The patient was without recurrence of his neoplasm
after 1-year follow-up.
3. Pathologic findings
3.1. Gross findings
A parotid gland with an attached ellipse of facial skin
measuring 7 × 7 × 6.5 cm was received. The gland was
largely replaced by a yellow-tan firm mass measuring 3.5 ×
3 × 2.5 cm, with a 5 × 4.4 × 4–cm adjacent cystic and
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Annals of Diagnostic Pathology 13 (2009) 114–118
⁎Corresponding author. Tel.: +1 716 859 2140; fax: +1 716 859 1853.
E-mail address: firstname.lastname@example.org (X. Fang).
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hemorrhagic area. The tumor was well circumscribed but
not encapsulated. There was only a thin rim of unremark-
able parotid tissue at periphery of the tumor (Fig. 1).
3.2. Microscopic findings
Review of the biopsy slides submitted from the local
medical center identified numerous multinucleated OGCs
distributed in a background of MNCs. The stroma was
hyalinized and focally chondromyxoid.
The total parotidectomy specimen was composed of
approximately 65% OGCs and MNCs, morphologically
similar to that of the biopsy tissue. Thirty-five percent of
the tumor also demonstrated a component of classic high-
grade salivary duct carcinoma, predominately located in
the cystic and hemorrhagic areas. A small amount of
benign salivary tissue remained at the periphery of the
The giant cell portion of the tumor was characterized by
OGCs evenly distributed among MNCs (Fig. 2). The OGCs,
which were morphologically bland and indistinguishable
from the osteoclasts of bone, had round ovoid nuclei, finely
granular chromatin, and small nucleoli. The number of
nuclei per cell ranged from 6 to 14. The sizes of MNCs
were variable: the nuclei in some areas were uniform, oval
to round, with vesicular chromatin and inconspicuous
nucleoli, whereas in other areas, the nuclei were large,
irregular, and bizarre, with hyperchromatic chromatin and
prominent nucleoli. The mitotic rates were high in the
The carcinomatous portion of the tumor consisted of
ductal, cribriform, and cystic structures with frequent central
comedo necrosis (Fig. 3). The neoplastic epithelial cells
showed hyperchromatic pleomorphic nuclei and prominent
nucleoli. The mitoses were numerous. Lymphatic invasion
was evident. The OGCs were sparse to absent in the
carcinomatous area. At the interface, the components of giant
cells and carcinoma were merged together.
Fig. 1. The tumor is firm and well circumscribed with a pink-tan cut surface
and peripheral cystic and hemorrhagic changes.
Fig. 2. Multinucleated giant cells resembling osteoclasts of bone are
distributed among neoplastic MNCs (high power).
Fig. 3. Components of a typical salivary duct carcinoma infiltrating a
hyalinized fibrous stroma (medium power).
Fig. 4. Immunohistochemical staining of CD68. Both multinucleated giant
cells and MNCs are positive for this marker (high power).
115 X. Fang et al. / Annals of Diagnostic Pathology 13 (2009) 114–118
The stroma of the tumor was largely composed of
fibrous tissue, bundles of hyalinized collagen, and focal
chondromyxoid matrix. Large areas of necrosis and
hemorrhage were present throughout the tumor.
3.3. Immunohistochemical findings
Both OGCs and scattered MNCs were positive for
vimentin and CD68 (Fig. 4). In addition, admixed within
the mononuclear component were scattered cells positive for
androgen receptor and epithelial markers (Fig. 5), including
cytokeratin AE1/AE3, cytokeratin CAM 5.2, and epithelial
membrane antigen (EMA). Those 2 components were
negative for S100, melan-A, carcinoembryonic antigen,
and osteocalcin. The component of salivary duct carcinoma
was reactive to antibodies of cytokeratin 7 (Fig. 6) and
Extraskeletal neoplasms containing OGCs have been
reported in many organs, including the breast , uterus
, lung , pancreas , kidney , and soft tissue
. Occurrence of similar tumors in the salivary gland is
extremely rare. To our knowledge, there are 15 previously
reported cases in the English literature, and our case is added
for a total number of 16 (Table 1). Fourteen cases involve the
parotid gland, and 2 cases involve the submandibular gland.
Most patients (13/16) are men, and the ages of presentation
range from 28 to 92 years. The patients usually present with
symptoms of pain and a rapid growing mass. Facial nerve
involvement is not common and reported only in 2 cases.
Surgery with combined radiotherapy is the treatment of
choice. The prognosis is variable in the literature, with a
postoperational disease-free survival time ranging from
13 months to 6 years.
Grossly, the tumor sizes range from 1 to 8 cm, with a
mean dimension of 3.7 cm. Histologically, the tumor is
composed of OGCs evenly distributed among MNCs. In
9 of 16 cases, there is an associated carcinomatous
component. In the remaining 7 cases, the tumors are
composed of exclusive OGCs and MNCs. Most articles
describe different nuclear morphologies between OGCs
and MNCs. The former is cytologically bland, resembling
osteoclasts of bone, whereas the latter demonstrates a
spectrum of cytologic atypia from relatively bland
[1,2,5,7] to highly irregular and bizarre [1,5,8]. The
finding has lead to several studies on the histogenesis of
OGCs and MNCs. Eusebi et al  and Balogh et al 
discovered poorly formed cell junctions and numerous
microvilli on the surface of OGCs by electron micro-
scopy, features suggestive of epithelial cell origin. The
more recent studies [2,4,5,7] demonstrated expression of a
spectrum of histiocytic markers on OGCs, such as
lysozyme, α1-antitrypsin, and CD68, whereas cytokeratin
reactivity was consistently negative. The immunopheno-
typic patterns of OGCs in our case are in accord with the
findings of the recent studies. CD68 is known to express
in the cells originated from a monocytic phagocytic
system, including osteoclasts . As proposed by Tse
et al  and Donath et al , OGCs appeared to be
reactive giant cells derived from monocytic or histiocytic
stromal cells, likely representing host response to neo-
plasm [2,4,13]. We favor this theory and believe that the
discrepancy between the recent and some earlier studies
[1,8] could be due to the significant improvement of the
immunohistochemical techniques in the past decades.
Furthermore, OGCs are a rich source of regulatory
cytokine , which may act to chemoattract additional
mononuclear OGC precursors as well as influence the
biologic behavior of the neoplastic cells in an autocrine/
Fig. 5. Many MNCs demonstrate strong cytoplasmic staining for cytokeratin
AE1/AE3, whereas multinucleated giant cells are negative for this
cytokeratin (high power).
Fig. 6. The component of salivary duct carcinoma is diffusely and strongly
immunoreactive for cytokeratin 7 (medium power).
116X. Fang et al. / Annals of Diagnostic Pathology 13 (2009) 114–118
In contrast to GCT of bone, where OGCs are believed to
be of monocytic or histiocytic origin, the MNCs of salivary
gland GCT have demonstrated epithelial differentiation by
ultrastructural [1,8] and immunohistochemical studies
[2,7,8]. In our case, MNCs are positive for epithelial
markers including cytokeratinAE1/AE3, CAM 5.2, and
EMA, similar to the immunophenotype of adjacent salivary
duct carcinoma. The finding is in concord with other
studies [2,7,8] in which MNCs are viewed as poorly
differentiated carcinoma cells. In their reported case, Tse
et al  identified similar genotypic profiles and a shared
mutation of the same allele on chr17p13 between MNCs
and the salivary duct carcinoma component, suggesting a
similar histogenesis of those 2 components.
The most important differential diagnosis that needs to be
made with this tumor is carcinoma vs sarcoma, which may
result in a completely different therapeutic approach. It is of
note that in the reported cases, almost half (44%) were
composed of exclusive OGCs and MNCs, without conven-
tional salivary carcinomatous components. Furthermore,
even when GCTs did contain a various amount of
carcinomatous components, the latter might be too scanty
to be sampled in a small biopsy. In our case, the open biopsy
was misinterpreted as an extraosseous osteosarcoma based
on the exclusive components of OGCs and MNCs. There-
fore, awareness of the existence of such tumor in the salivary
gland and a diligent sampling of the specimen cannot be
overemphasized to avoid a misdiagnosis of soft tissue tumor.
In difficult cases, immunohistochemical studies are highly
valuable to identify epithelial nature of MNCs.
In summary, we are reporting a rare case of GCT of the
salivary gland with associated components of salivary duct
carcinoma. In agreement with the recent studies, the
morphology and immunohistochemistry of our case show
that OGCs are most likely derived from monocytic or
histiocytic cells and probably represent a host response to
neoplasm. On the other hand, MNCs are of epithelial
origin, representing poorly differentiated carcinoma com-
ponents. It is important to pay careful attention to the
epithelial nature of the latter component to avoid a
misdiagnosis of mesenchymal neoplasm, such as extraoss-
eous GCT or extraosseous osteosarcoma.
Summery of reported features of GCTs of the salivary gland
Size (cm)Site Carcinomatous
IHCs of OGCs IHCs of MNCsTreatment Outcome (mo)
Tse et al 
43/M 7 × 7 × 6.5Pa Salivary duct
+: CD68, vimentin;
+: Vimentin, CD68;
−: keratin, antitrypsin
+: Vimentin, CD68, EMA,
CKAE1/3; −: CEA
+: Vimentin, CD68, CEA,
−: keratin, CAM 5.2
75/M 1.1PaSurgery NA
Donath et al  82/M
75/M 5.5 × 3.3SmCa ex pleomorphic
Grenko et al  66/F5PaCarcinosarcoma with
+: Vimentin SurgeryDOD/13
Itoh et al 
et al 
8 × 6
3 × 2.5 × 2.5 Pa
−: epithelial markers
92/M2 × 1.5 × 1.5 Pa +: Antitrypsin,
+: EMA; −: keratin
et al 
Ellis et al 
67/M6 × 5 × 4Pa Infiltrating intraductal
−: Epithelial and
et al 
1 × .8 × .8
2 × 1.5
Ca ex pleomorphic
IHC indicates immunohistochemical study; Pa, parotid gland; Ca, carcinoma; CKAE, cytokeratin AE; CEA, carcinoembryonic antigen; NED, no evidence of
disease; NA, not available; DOD, died of disease.
117X. Fang et al. / Annals of Diagnostic Pathology 13 (2009) 114–118
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