Malignant tumors
Clear cell odontogenic carcinoma

Author: Anthony Martinez, M.D. (see Authors page)
Editor: Kelly R. Magliocca, M.D.

Revised: 28 July 2016, last major update July 2016

Copyright: (c) 2003-2016,, Inc.

PubMed Search: Clear cell odontogenic carcinoma
Cite this page: Clear cell odontogenic carcinoma. website. Accessed October 20th, 2016.
Definition / General
  • Rare, malignant, translocation associated odontogenic epithelial neoplasm composed of nest of clear cells and fibrous, hyalinized stroma
  • EWSR1 rearrangements found in > 80% of cases (Am J Surg Pathol 2013;37:1001)
  • Clear cell odontogenic carcinoma (CCOC), clear cell odontogenic tumor
  • Previously called clear cell ameloblastoma
  • Considered benign by WHO of 1992, but due to its high potential for regional spread and distant metastases, it was reclassified as malignant in 2005
  • Rare, < 100 cases reported
  • Most common in 5th to 6th decades
  • Mean age ~ 60 years
  • More common in females (1.5:1 to 2:1)
  • First described in 1980's as jaw tumors that resembled metastatic clear cell renal carcinoma (Head Neck Surg 1985;8:115)
  • Mandible most common site (75%)
  • Soft tissue involvement common as lesion often perforates bone
  • Unknown, as with many translocation tumors, lesion tends to pursue a line of differentiation rather than originate from a particular line of derivation
  • However, the tumor cells resemble clear cell rests of primitive dental lamina that are frequently in the same locations
Clinical Features
  • Often presents as jaw swelling with loosening of the teeth
  • Can be painful, asymptomatic or associated with paresthesias
  • Diagnosis dependent on clinical, radiologic and pathologic correlation
Radiology Description
  • Poorly defined radiolucency
  • May show cortical destruction of bone
Prognostic Factors
  • Recurrence rate of 30% of resected and 87% of curetted/enucleated lesions
  • Metastases to lymph nodes, lung and bone
  • Up to 25% die of disease
Case Reports
  • Must tailor surgical treatment to overall clinical and image findings, but often involves a composite / en bloc resection
Clinical Images

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Buccal cortical expansion
with ulceration

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Intraoral ulcerated growth

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Bone destruction in
symphysis region

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Fig A: radiolucent lesion
in posterior segment

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Ill defined
radiolucent lesion

Gross Images

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Composite resection

Micro Images

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Nests of clear cells

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Various H&E

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Congo red stain

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Tumor cells

Positive Stains
Molecular / Cytogenetics Description
Molecular / Cytogenetics Images

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Interphase cells

Differential Diagnosis
  • May vary based on biopsy sample size and whether histology is monophasic (predominantly clear cell), biphasic or ameloblastomatous:
Monophasic (predominantly clear cell) or focal biphasic appearance:
  • Clear cell carcinoma of salivary gland
    • More common in minor salivary glands (~80%), particularly base of tongue, palate, floor of mouth, tongue and buccal mucosa in oral cavity/oropharynx
    • The nests or cords lack focal palisading of basal cells ("ameloblastic") seen in CCOC
    • Both lesions show EWSR1 rearrangements
    • May represent "salivary gland analogue"

  • Clear cell variant of calcifying epithelial odontogenic tumor (CEOT)
    • Benign epithelial odontogenic neoplasm, clear cell variant may be composed primarily of clear cells
    • Occurs in posterior mandible, intra-osseous location
    • Variably sized polyhedral eosinophilic epithelial cells with distinct cell borders are arranged in small clusters, trabeculae, islands or a sheet like pattern
    • Nuclear pleomorphism is expected, but without appreciable mitotic activity
    • Eosinophilic amyloid-like matrix material is haphazardly deposited in association with the tumor islands, and calcified concentric profiles (Liesegang rings) are often identified
    • Ancillary studies show the epithelial cells of CEOT highlight with cytokeratin AE1/3, CK5/6 and p63, and amyloid-like material exhibits apple green birefringence when stained with Congo red and viewed with polarized light

  • Sclerosing odontogenic carcinoma
    • Rare and controversial entity, described in 2008
    • Low grade odontogenic carcinoma, locally aggressive
    • Infiltrating single file strands, cords and nests of cuboidal or polygonal epithelial cells with cytoplasmic clearing, similar to signet ring change
    • No prominent pleomorphism or mitotic figures; no necrosis
    • Skeletal muscle and perineural infiltration with stromal sclerosis are characteristic

  • Clear cell renal cell carcinoma (metastatic)
    • Usually a known history of renal cell carcinoma, which is PAX8+

  • Epithelial-myoepithelial carcinoma
    • Malignant biphasic tumor with an inner duct-like epithelial component and an outer S100+ myoepithelial component
    • Usually occurs in major salivary glands
    • CCOC has only a clear cell epithelial component, and is S100 negative

  • Mucoepidermoid carcinoma, clear cell variant
    • Malignant epithelial tumor with variable amounts of mucous, epidermoid and intermediate cells
    • Mucocytes are mucicarmine+
    • Can be associatied with MAML2 rearrangement and NOT EWSR1

  • Sinonasal renal cell-like adenocarcinoma (SRCLA)
    • May be difficult to differentiate, but clear cell tumors involving the maxillary or palatal structures require consideration of a sinonasal neoplasm with secondary involvement of the oral region (Int J Clin Exp Med 2014;7:5469)
    • Rare tumor characterized by a clear cell glandular proliferation, most often involving the nasal cavity, associated with a favorable clinical course
    • Has round cells with clear cytoplasm and a prominent nucleolus arranged in a follicular pattern
    • A tubular arrangement and papillary architecture of the clear cell proliferation have also been described
    • No mucinous or myoepithelial differentiation, no necrosis, no hyalinization of stroma
    • SRCLA vs. hyalinizing clear cell carcinoma of salivary gland (HCCC): no stromal hyalinization, no stromal vascularity; often has larger clear cells than HCCC and CCOC; has robust CAIX immunostaining vs. focal positive in HCCC; negative for EWSR1 rearrangement

Ameloblastomatous appearance:
  • Desmoplastic ameloblastoma
    • Dense collagenous stroma with compressed, angular islands of basaloid odontogenic epithelium

  • Squamous odontogenic tumor
    • Benign tumor of odontogenic squamous epithelium
    • Very rare; thought to arise from rests of Malassez in periodontal ligament
    • No peripheral palisading or stellate reticulum

  • Odontogenic fibroma
    • Rare tumor, and poorly described in literature
    • Loose to dense collagenous stroma with small, rounded or elongated islands of bland odontogenic epithelial islands
    • Islands not elongated, interconnected or arborizing
    • Minimal clear cell change