Archives of Oral Sciences & Research
Clear Cell Odontogenic Carcinoma: A Diagnostic Dilemma
S Hemavathy *, Chandrakala Jǂ, Sahana N.S†, Suresh Tǂ, Vinay Kumar D‡, Mohammed Asif‡
Rohit Kumar K‡
ABSTRACT:
Clear cell odontogenic carcinoma is a rare odontogenic tumor occurring in the anterior region
of the mandible in 5th–7th decades and shows a female prevalence. The reports in the literature,
however, all have indicated that this tumor exhibits an aggressive behavior characterized by
infiltrative local growth, recurrence or metastases. In this article, we report a case of clear cell
odontogenic carcinoma in a 20 year old female, a rare case which occurred in the maxilla,
focusing on their histologic, immunophenotypic, and differential diagnostic features. The
aggressive potential of this neoplasm is well documented and resection with negative margins
is the treatment of choice.
AOSR 2013;3(2):135-143
Keywords: Clear cell odontogenic carcinoma; clear cells; Clear cell ameloblastoma;
Odontogenic tumors; Clear cell tumors; Immunohistochemistry
* Professor, Department of Oral Pathology, Govt. Dental College, Bangalore
ǂ Reader, Department of Oral Pathology, Govt. Dental College, Bangalore
† Professor and Head, Department of Oral Pathology, Govt. Dental College, Bangalore
‡ Post Graduate Student, Department of Oral Pathology, Govt. Dental College, Bangalore
A
k
INTRODUCTION
Clear cell odontogenic carcinoma (CCOC)
World
is a rare odontogenic tumor associated
classification.1 Because these tumours
with
behavior,
have an aggressive and destructive growth
metastasis and low survival. CCOCs were
capacity and may metastasis to distant
formerly called Clear cell ameloblastoma
organs and lymph nodes, the 2005 WHO
or Clear cell odontogenic tumors and were
classification listed them as malignant
considered benign tumors in the 1992
tumors characterized by sheets and islands
aggressive
clinical
135
Health
Organization
(WHO)
Clear cell odontogenic carcinoma
cells.2
consistency. Panoramic radiograph showed
Piattelli et al was the first to theorize that
a multilocular radiolucency extending
the CCOC is a distinct and separate entity
from 24 to 27 with poorly defined
and
margins. (Fig. 2)
of
vacuolated
not
a
and
clear
clear
cell
variant
of
ameloblastoma.3
Case Report:
A 20 year- old female reported to our
department with a complaint of painless
swelling in the posterior left palate region
Fig 2: Radiograph shows multilocular
radiolucency extends from 24 to 28 region.
since three years. Swelling extended from
first premolar to second molar region,
Based on clinical and radiographic features
measuring around 3x2cm. Teeth adjacent
the lesion was provisionally diagnosed as
to the lesion were mobile. The overlying
salivary gland tumor. An incisional biopsy
mucosa was normal with no ulceration.
of the lesion was performed and sent for
(Fig. 1) There was no lymph node
histopathologic evaluation. Microscopic
involvement and no associated sensory
examination of the tissue showed a
neoplasm composed of epithelial cells
arranged in sheets, cords or nests of
monomorphic, plump, polygonal-to-round
clear cells with eccentric nuclei, often
separated by hyalinized
Fig 1: Intra oral view showing Swelling
septa.
extends from first premolar to second molar
region
The
cells
fibrovascular
adjacent
to
the
fibrovascular septa were cuboidal to
columnar with eosinophilic cytoplasm,
symptoms. On physical examination the
while those in the center of the nests were
lesion was non tender and soft in
136
S Hemavathy et al
larger and polygonal, with abundant clear
cytoplasm (Figure 3). The lesion was
diagnosed as clear cell tumor.
Fig 5: H and E section showing sheets of
polyhedral cells with eosinophilic cytoplasm
Patient was surgically treated and the
resected
maxilla
was
sent
for
histopathological examination. Multiple
selected areas of the resected tumor were
Fig 3: H and E section shows biphasic pattern
sent
containing clear cells and hyperchromatic
for
processing.
histopathological
Postoperative
examination
showed
polygonalcells which exhibits eosinophilic
tumor morphology similar to incisional
cytoplasm
biopsy.
A variety of tumors containing clear cells
such as odontogenic, metastatic, and
salivary tumors were considered in the
differential diagnosis. Special stains were
carried out to rule out salivary gland
tumors. The tumor cells were negative for
alcian blue but the abundant, clear
cytoplasm
Fig 4: H and E section showing islands of clear
cells with eccentric.
was
strongly positive
for
periodic acid-Schiff (PAS), this PAS
positivity was diastase sensitive indicating
137
Clear cell odontogenic carcinoma
intra
cytoplasmic
Immunohistochemical
glycogen.
studies
for
local
recurrence,
evidence
of
were
pulmonary and lymph node metastases and
performed. The tumor cells were negative
tumor related deaths necessitated a change
for vimentin, S100 protein, desmin, and
in their classification and nomenclature
smooth muscle actin. Focal positive
and is now called Clear cell odontogenic
staining for epithelial membrane antigen
carcinoma.6-10 A recent review of literature
was noticed. Tumor cells stained diffusely
of the 43 cases reported11 so far showed
and intensely for CK19. A diagnosis of
that the male: female ratio was 3:1, mean
clear cell odontogenic carcinoma was
age at presentation was 58 years (range
given.
17–89 years), the average period of
follow-up was 5.5 years (range 0.5–21
DISCUSSION
years), mandible was the most favored
Clear cell lesions in the head and neck
location(84%). The clinical features of the
evoke a broad differential diagnosis that
present case is in general agreement with
may encompass a variety of odontogenic,
those of the previous reports, relatively
metastatic and salivary tumors that may be
younger age (20 years) of the patient at
included in the differential diagnosis for
diagnosis and a more apparent predilection
4
CCOC.
for females. In contrast with our case being
In 1985, Hansen et al., reported a locally
reported where the lesion occurred in the
aggressive odontogenic neoplasm, and
posterior region of the maxilla, studies
named it clear cell odontogenic tumor5.
have shown that the anterior portions of
This neoplasm was initially thought to be
the jaws especially the mandible are most
devoid
frequently affected.
of
malignant
potential
and
classified as benign1. Subsequent reports
Histopathologically, CCOCs may show
of their aggressive behavior, predilection
one or more of three architectural patterns:
138
S Hemavathy et al
biphasic,
monophasic,
and
within the cytoplasm. Metastatic tumors
ameloblastomatous. The most common
(classic clear cell renal cell carcinoma,
biphasic
which
pattern
of
tumor
growth
can
be
identified
by
its
comprises of nests of cells with clear
characteristically rich vascular pattern and
cytoplasm admixed with cells containing
its immunoreactivity for cytokeratins and
eosinophilic cytoplasm. The monophasic
vimentin and lack of reactivity for S-100
pattern comprises only of clear cells, while
protein; and amelanotic melanoma, which
the ameloblastomatous pattern resembles
reacts for HMB-45, S-100 protein and
the growth pattern of ameloblastoma with
other
nests of cells showing central cystic
odontogenic
change and squamous differentiation, and
clearing of their constituent cells. Such
peripheral nuclear palisading with reverse
tumors
polarity.10 In our case report the biphasic
odontogenic
architectural pattern is evident.(fig:3,4,5)
ameloblastoma. While the former is
prominent
cytoplasmic
includes
intraosseous
salivary
tumors,
mucoepidermoid
tumors
include
identified
The differential diagnosis of jaw tumors
with
melanoma
Other
may
show
also
calcifying
tumor
by
markers).
and
the
epithelial
clear
presence
cell
of
psammomatous calcifications and amyloid
clearing
deposits, the latter may be difficult to
gland
distinguish from CCOC. In fact, some
carcinoma,
authors
distinguished by its triphasic architecture
think
ameloblastomas
comprised of mucous cells, squamoid
that
and
clear
cell
CCOCs
may
represent a clinico-pathological continuum
cells, and intermediate cells.12 In the
of a single neoplastic entity.13 In the
present tumor the clear cells contained
present case Immunocytochemically, the
diastase-digestible, PAS-positive granules,
tumor cells showed positive staining for
negative for Alcian blue, indicating the
cytokeratin,
presence of glycogen rather than mucin
139
CK-19
and
epithelial
Clear cell odontogenic carcinoma
membrane antigen. Expression of wide-
The histologic evidence of tumor invasion,
spectrum of cytokeratin and epithelial
frequent or multiple local recurrences,
membrane antigen has been assessed in
regional and/or distant metastatic potential,
various odontogenic lesions14,15, and CK-
and an occasional fatal clinical course, as
19 has been shown to react with all kinds
demonstrated here and in previous reports,
of odontogenic epithelial cells.16,17 In
all indicate that this group of clear cell
salivary glands and their tumors, however,
odontogenic tumors should be considered
only ductal cells exhibit focal expression
as,
of
CK-19.18
Thus,
at
least,
low-grade
malignancies.1,7,8,19,20
the
immunocytochemical profile which was
The overall recurrence rate for these
performed in our case suggests that they
tumors are 55% and local recurrence rates
are of odontogenic epithelial origin. (Fig: 6
were higher (80%) for curettage alone than
& 7)
for resection (43%)11. At 1-year follow-up
of
our
patient
is
well and
free
of
recurrence.
CONCLUSION
CCOC
although
rare,
should
be
considered in differential diagnosis of jaw
tumors
with
prominent
clear
cell
component. Factors such as size of the
lesion, soft tissue involvement, lymph
node metastasis and most importantly, the
Fig 6 and 7: IHC findings: Tumor cells
stain diffusely and intensely positive for
CK19
presence or absence of positive surgical
margins should be considered during
140
S Hemavathy et al
treatment planning. Currently, treatment is
4. Mesquita RA, Lotufo MA, Sugaya
aimed at achieving wide surgical resection
NN, et al. Peripheral clear cell variant
with tumor-free margins, and loco-regional
of calcifying epithelial odontogenic
control by lymph node resection and local
tumor:
radiation.
immunohistochemical
A long-term follow-up is
Report
of
a
case
and
essential as these tumors may recur locally
investigation. Oral Surg Oral Med
or present with late distant metastases.
Oral Pathol Oral Radiol Endod. 2003;
95:198–204.
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CORRESPONDENCE
Dr Chandrakala J, MDS
Associate Prefessor
Department of Oral Pathology
GDCRI, Bangalore
Ph- +919242468024
E-mail- [email protected]
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