[Downloaded free from http://www.cancerjournal.net on Saturday, August 7, 2021, IP: 157.33.244.

95]

Correspondence

Clear cell odontogenic carcinoma: A rare

case report with emphasis on differential
diagnosis
ABSTRACT Uma Vasant
Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic malignancy with a female predilection, typically presenting as Datar,
swelling in anterior region of mandible. CCOC was classified as a malignant neoplasm of odontogenic origin by the WHO in 2005 as Mamata Sharad
it exhibits an aggressive growth pattern, local recurrence, and tendency of distant metastasis. Histologically, CCOC is characterized Kamat,
by sheets and islands of vacuolated/clear cells. Since clear cells are present in few odontogenic tumors, salivary gland neoplasms, Sampada Shriram
and metastatic tumors to the jaws; presence of clear cells in a lesion of head and neck area poses a diagnostic challenge. Knowledge Kanitkar,
about the clinical course, histopathologic pattern, and immunoprofile of CCOC aids in differentiating it from other clear cell tumors. Sanjay Satappa
Herein, we present a case of CCOC in anterior mandibular region of 60‑year‑old female patient with an emphasis on its differential Byakodi1
diagnosis from other clear cell lesions of the jaws. Departments of
Oral Pathology
and Microbiology
KEY WORDS: Anterior mandible, clear cells, clear cell odontogenic carcinoma, immunohistochemistry and 1Oral and
Maxillofacial Surgery,
Bharati Vidyapeeth
Deemed University
INTRODUCTION orthopantomogram [Figure 1b], a well‑defined Dental College and
corticated unilocular radiolucent lesion extending Hospital, Sangli,
Clear cell odontogenic carcinoma (CCOC) is a from tooth 33 to tooth 43 was seen. Root divergence Maharashtra, India
low‑grade odontogenic carcinoma showing cells of the central and lateral incisors was observed.
For correspondence:
with clear cytoplasm arranged in sheets and Findings of general physical examination, Dr. Uma Vasant Datar,
islands.[1] Most of the CCOC typically present as ultrasonography (USG) of abdomen and chest Department of
swelling in anterior region of the mandible in radiographs were noncontributory. Based on Oral Pathology
elderly female patients. Radiographically, it exhibits clinical and radiographic features, a provisional and Microbiology,
ill‑defined unilocular or multilocular radiolucency diagnosis of odontogenic cyst was considered, the Bharati Vidyapeeth
Deemed University
with tendency to cause bone destruction and tooth lesion was enucleated and the specimen was sent Dental College and
resorption.[1,2] Detailed literature search suggests for histopathological diagnosis. Hospital, Sangli,
that only 96 cases of CCOC have been reported Maharashtra, India.
till date.[3‑9] The present case report discusses the Histopathological examination revealed a poorly E‑mail: dataruv@
clinical, histological, and immunohistochemical circumscribed tumor of odontogenic epithelium. gmail.com
characteristics of CCOC and sheds light on its The tumor cells were arranged in the form of
diagnostic differences from the other clear cell islands and chords demonstrating a biphasic
lesions. cell pattern [Figure 2a]. One cell population was
composed of clear cell having clear to faintly
CASE REPORT eosinophilic cytoplasm [Figure 2b]. The other
cell population is composed of basaloid cells
A 60‑year‑old female patient presented with a with minimal amount of cytoplasm. Focally,
complaint of swelling in the anterior region of ameloblast‑like cells were noted [Figure 2c]. The Access this article online

the mandible since 1 year. Intraoral examination Website: www.cancerjournal.net

revealed a well‑defined, dome shaped, nontender DOI: 10.4103/0973-1482.187381

swelling of 3 cm in diameter, extending from
tooth 33 to tooth 43. Both the buccal and lingual
cortical plate expansions were evident [Figure 1a].
Regional lymph nodes were not palpable. On
This is an open access article distributed under the terms of the Creative Commons PMID: ***
Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix,
Quick Response Code:
tweak, and build upon the work non‑commercially, as long as the author is credited
and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com

Cite this article as: Datar UV, Kamat MS, Kanitkar SS, Byakodi SS. Clear cell odontogenic carcinoma: A rare case report
with emphasis on differential diagnosis. J Can Res Ther 2017;13:374-7.

374 © 2017 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow
[Downloaded free from http://www.cancerjournal.net on Saturday, August 7, 2021, IP: 157.33.244.95]
Datar, et al.: Clear cell odontogenic carcinoma
clear cells were Periodic acid–Schiff positive and diastase
labile [Figure 3]. The cells were negative for mucicarmine stain.
The tumor cells were immunoreactive for pancytokeratin,
epithelial membrane antigen p63. The tumor cells were
nonreactive for S100, vimentin, desmin, alpha smooth muscle
actin (SMA), calponin, and calretinin. Ki 67 [mib1] proliferation
index was 40% [Figure 4]. With the histopathological features
and immunohistochemical profile, the diagnosis of CCOC was
established, and surgical resection was planned.
DISCUSSION
CCOC is a rare odontogenic tumor. The histogenesis of CCOC is
unclear literature suggests that clear cells in jaw lesions originate
from dental lamina or cell rests of Malassez.[2] It is suggested
that the presence of clear cells is an attempt to recapitulate
the presecretory phase of ameloblast with the accumulation
of glycogen.[6] Literature review reveals that CCOC commonly
occurs in the sixth decade of life (range 17–89 years).[8] CCOC
characteristically has female preponderance with male:female
ratio 1:1.8 and affects mandible more frequently than maxilla.[5]
Clinically, it presents as asymptomatic, slow growing swelling
of long duration with a mean size of 4 cm in diameter; however,
cases with pain, tooth mobility, paresthesia, and nonhealing
ulcerations have been reported.[3] Radiographically, CCOC
manifests as either unilocular or multilocular radiolucency
which may be well or poorly demarcated.[5] In the present case,
a well‑defined, well corticated, unilocular radiolucency with
divergence of associated teeth was observed.
Histopathologically, CCOC demonstrates three distinct patterns
namely biphasic, monophasic, and ameloblastomatous.
a b
Figure  1:  (a) Intraoral photograph of well defined, dome shaped
swelling in the mandibular anterior region, (b) orthopantomogram
showing well corticated, unilocular radiolucency extending from tooth
33 to tooth 43
a b
Figure 3: (a) Photomicrograph depicting clear cells with Periodic acid–
Schiff positive granules (Periodic acid–Schiff, ×40), (b) photomicrograph
showing diastase labile clear cells (Periodic acid–Schiff with
diastase, ×40)
Journal of Cancer Research and Therapeutics - Volume 13 - Issue 2 - April-June 2017
Biphasic type is the most common histological pattern
that shows two distinctive cell population namely clear
cells and basaloid cells. The “clear cells” show abundant
clear to faintly eosinophilic cytoplasm, distinct cell
membrane, central/eccentric uniform dark staining nuclei,
and lack significant pleomorphism and mitotic activity.[1,3,8]
The other cell type is dark staining basaloid cells with
scant eosinophilic cytoplasm. Monophasic pattern consists
entirely of clear cells. Ameloblastomatous pattern is least
common with the presence of clear cells centrally and
peripherally palisaded ameloblast‑like cells. [3‑7] Rarely,
a combination of different histologic patterns can be
encountered.[7] In the present case, predominantly biphasic
pattern was noted, but focally ameloblastomatous pattern
was evident [Figure 2c and d].
a b
c d
Figure  2: (a) Photomicrograph showing tumor cells arranged
in form of islands and chords in hyalinized connective tissue
stroma  (H  and  E, ×4), (b) tumor islands showing biphasic pattern
with centrally placed clear cells and peripheral basaloid cells
(H and E, ×10), (c) tumor islands showing peripheral ameloblast‑like
cells (H and E, ×40), (d) photomicrograph showing central clear cells
with centric small basophilic nucleus, distinct cell membrane and clear
cytoplasm (H and E, ×40)
a b
c d
Figure 4: (a) Photomicrograph of intense cytokeratin expression by
tumor cells  (×40),  (b) photomicrograph of moderate expression of
epithelial membrane antigen by tumor cells (×40), (c) Ki 67 positive
tumor cells (×40), (d) strong expression of p63 by tumor cells (×40)
375
[Downloaded free from http://www.cancerjournal.net on Saturday, August 7, 2021, IP: 157.33.244.95]

Datar, et al.: Clear cell odontogenic carcinoma

Clear cells are hallmark but not the pathognomonic feature of
CCOC. They are noted in odontogenic, salivary, melanotic, renal,
thyroid, and prostate tumors. Thus, the differential diagnosis of
CCOC evokes a broad range of tumors with diverse histogenesis
and biological behavior. The differentiation of these tumors
is confounding because of the considerable overlap in their
histologic features, thus posing a diagnostic challenge.[10,11]
The differential diagnoses for CCOC include clear cell variant of
calcifying epithelial odontogenic tumor (CCCEOT), ameloblastic
carcinoma, intraosseous variant of clear cell mucoepidermoid
carcinoma (CCMEC), hyalinizing clear cell carcinoma (CCC),
intraosseous variant of melanoma, metastatic tumors from
kidney, thyroid, and prostate [Table 1].[4‑13]
Absence of amyloid and Liesegang’s ring calcification in the
present case negated the possibility of CCCEOT. Lack of mucin
and negative staining for S100, alpha SMA, vimentin, and
calponin ruled out CCMEC.[5,10,11] Intraosseous location with
central bone destruction, presence of palisaded peripheral cells,
differentiated the present case from CCC.[6] Absence of sinusoidal
vascularity, intramural hemorrhage, noncontributory findings
of USG abdomen and chest radiographs ruled out the possibility
of metastatic renal cell carcinoma.[13]
Till date, only one report has evaluated the proliferative index
of CCOC to be 35.2 cells per high power field (HPF), in the
present case the proliferative index was 40 cells per HPF.[3] A

Table 1: Differential diagnoses of clear cell odontogenic carcinoma

Lesion Nature of Cause of Growth pattern Cytologic features Special stains Immunoprofile
clear cells cytoplasmic of clear cells
clearing
CCOC Glycogen rich Glycogen Infiltrative. Monophasic, Central or eccentric Clear cells EMA+
presecretory biphasic and nuclei abundant are PAS D−ve CK 19+
ameloblast ameloblastomatous are cytoplasm mucicarmine−ve Calretinin +/−
the three growth patterns
observed
Tumor islands/nests of
clear cells are separated
by stroma
Clear cell Tumor Degenerative Well circumscribed Pale staining clear Clear cells show ‑
variant of CEOT cells are of process/ pseudoglandular pattern cells with dark nuclei PAS D+/−
odontogenic cytodiffrentiation/ (with abundant clear cells Amyloid deposits
epithelial glycogen and amyloid deposits) in the stroma
origin accumulation show apple green
in tumor cells birefringence with
congo red
Mucoepidermoid Intermidiate, Glycogen and Infiltrative. Multiple cystic Pale basophilic Clear cells PAS CK7, CK19
carinoma mucinous mucin spaces lined by mucous, foamy cytoplasm D+/−, mucous cell
cells epidermoid, intermediate population stains
and clear cells positive for alcian
blue
Myoepithelial Myoepithalial Glycogen Infiltrative, lobules, nests,
Polygonal/spindle Clear cells are S100, alpha SMA,
carcinoma cells trabaculae and fascicles with variable degree PAS D–ve calponin, vimentin
of clear cells of nuclear atypia and HMWCK
Clear cell Ductal cells Glycogen Infiltrative; clear cells in
Polygonal cells with Clear cells are PanCK
carcinoma solid/trabacular pattern in
water clear cytoplasm PAS D+/−
hyalinized stroma and centric/eccentric
nuclei
Epithelial Myoepithelial Glycogen Infiltrative; solid, cystic, Polygonal cells with Clear cells are Calponin, CK,
myoepithelial cells spindle, tubular, organoid, clear cytoplasm, PAS D–ve EMA, S100
carcinoma nodular papillary cribriform distinct outline,
pattern ductal structures centrally placed
lined by inner cuboidal and nucleus
outer myoepithelial cells
Acinic cell Salivary Artifactual/paucity Infiltrative broad fronts, Peripherally located PTAH+ S100, PanCK,
carcinoma acinar cells of organelles/ microcystic pattern nuclei, sparse Vimentin,
transformation of basophilic granules in transferrin, alpha
tumor cells some areas 1‑antitrypsin,
CEA, GFAP
Metastatic renal Renal Lipid Infiltrative, solid/organoid Epithelial cells Sudan black, CD10
cell carcinoma epithelial accumulation growth pattern sinusoidal with small round oil red O+ve on
cells vascular network and hyperchromatic frozen sections
hemorrhage nucleus and clear
cytoplasm
Amelanotic Melanocytes ‑ Infiltrative; nests sheets of Celar to finely Masson’s Fontana, S 100, HMB 45,
melanoma clear cells vacuolated cytoplasm Schmorl’s stain Melan A
CCOC=Clear cell odontogenic carcinoma, PAS=Periodic acid–Schiff, PASD=Periodic acid Schiff with diastase, EMA=Epithelial membrane antigen. CK=Cytokeratin,
α SMA=Alpha smooth muscle actin, HMWCK=High molecular weight CK, PTAH=Phosphotungstenic acid hematoxylin, CEA=Carcinoembryonic antigen, CD=Cluster
of differentiation, HMB 45=Homatropine methyl bromide, CEOT=Calcifying epithelial odontogenic tumor

376 Journal of Cancer Research and Therapeutics - Volume 13 - Issue 2 - April-June 2017
[Downloaded free from http://www.cancerjournal.net on Saturday, August 7, 2021, IP: 157.33.244.95]
Datar, et al.: Clear cell odontogenic carcinoma
recent literature review[3] suggests that CCOC has potential for
multiple recurrences (41%), metastasis (31%), thus demanding
an aggressive treatment approach and long‑term surveillance.
Surgical resection with wide margins is the treatment of choice
for CCOC, with adjuvant radiotherapy for cases showing
perivascular and perineural invasion. The cases treated initially
with conservative surgery showed higher recurrence rate as
compared to those treated with surgical resection (86.7%
vs. 29%).[9] Hence, CCOC is now considered as a high grade
odontogenic malignancy.
CONCLUSION
Differentiating CCOC from other clear cell tumors of head and
neck is crucial. Clinical presentation and histopathological
pattern primarily aided in the diagnosis of CCOC in our case.
Special stains and immunoprofiling acted as an adjuvant to
rule out the other clear cell tumors. CCOC warrants a close
and long‑term follow‑up since it has a low survival rate and
recurrence and metastasis were reported as late as 20 years
after first intervention.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Bang G, Koppang H. Clear cell odontogenic carcinoma. In Barnes L,
Eveson JW, Reichart P, Sidransky, editors. World Health Organization
Journal of Cancer Research and Therapeutics - Volume 13 - Issue 2 - April-June 2017
Classification of Tumours. Pathology and Genetics of Head and Neck
Tumours. Lyon: IARC Press, 2005. p. 292.
2. Walia C, Chatterjee RP, Kundu S, Roy S. Clinical enigma: A rare
case of clear cell odontogenic carcinoma. Contemp Clin Dent
2015;6:559‑63.
3. Loyola AM, Cardoso SV, de Faria PR, Servato JP, Barbosa de Paulo LF,
Eisenberg AL, et al. Clear cell odontogenic carcinoma: Report of 7
new cases and systematic review of the current knowledge. Oral
Surg Oral Med Oral Pathol Oral Radiol 2015;120:483‑96.
4. Ganvir SM, Gajbhiye NY. An unusual presentation of clear cell
odontogenic carcinoma in mandibular anterior region. J Oral
Maxillofac Pathol 2014;18:442‑8.
5. Swain N, Dhariwal R, Ray JG. Clear cell odontogenic carcinoma of
maxilla: A case report and mini review. J Oral Maxillofac Pathol
2013;17:89‑94.
6. Bilodeau EA, Hoschar AP, Barnes EL, Hunt JL, Seethala RR. Clear cell
carcinoma and clear cell odontogenic carcinoma: A comparative
clinicopathologic and immunohistochemical study. Head Neck Pathol
2011;5:101‑7.
7. Avninder S, Rakheja D, Bhatnagar A. Clear cell odontogenic
carcinoma: A diagnostic and therapeutic dilemma. World J Surg Oncol
2006;4:91.
8. Slater LJ. Odontogenic malignancies. Oral Maxillofac Surg Clin North
Am 2004;16:409‑24.
9. Kalsi AS, Williams SP, Shah KA, Fasanmade A. Clear cell odontogenic
carcinoma: A rare neoplasm of the maxillary bone. J Oral Maxillofac
Surg 2014;72:935‑8.
10. Premalatha BR, Rao RS, Patil S, Neethi H. Clear cell tumours of the
head and neck. An overview. World J Dent 2012;3:344‑9.
11. Said‑Al‑Naief N, Klein MJ. Clear cell entities of the head and neck:
A selective review of clear cell tumors of the salivary glands. Head
Neck Pathol 2008;2:111‑5.
12. Chen CY, Wu CW, Wang WC, Lin LM, Chen YK. Clear‑cell variant of
calcifying epithelial odontogenic tumor (Pindborg tumor) in the
mandible. Int J Oral Sci 2013;5:115‑9.
13. Will TA, Agarwal N, Petruzzelli GJ. Oral cavity metastasis of renal
cell carcinoma: A case report. J Med Case Rep 2008;2:313.
377