Clear cell odontogenic carcinoma: A case report and literature review


Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic tumor of the jaw with a particular histology and a deceptive behavior. The clinical presentation may be misleading, that is why the contribution of incisional biopsy, molecular biology, immunohistochemistry and cytogenetics is essential in the diagnostic process.

This review article aims to discuss its various aspects, summarizing the currently published studies of CCOC to enhance the diagnosis and to present a case report of a 41-year-old man that presented to the Department of Maxillofacial Surgery at Gemelli University Hospital in Rome, Italy.


  • Clear cell odontogenic carcinoma is a rare odontogenic tumor of the jaw with a particular histology and a deceptive behaviour.

  • CCOC often presents itself as an asymptomatic, painless and slow-growing lesion.

  • The contribution of molecular biology, immunohistochemistry and cytogenetic are significant for the diagnosis.

  • Surgical resection with wide margins is the gold-standard treatment.


Clear cell odontogenic carcinoma (CCOC) is a rare intraosseous tumor of the jaw.

Clear cell changes have been identified in various benign and malignant tumors of epithelial, melanocytic, mesenchymal and hematopoietic origin but are perceived as a rare occurrence in the head and neck region. It was formerly defined as Clear cell odontogenic tumor (CCOT) or Clear cell ameloblastoma (CCA).

Hanson et al. were the first to describe this tumor in 1985 and they classified it as a benign odontogenic tumor. According to the World Health Organization (WHO) classification of odontogenic tumors in 1992, CCOC was classified as a benign neoplasm with the capacity of undergoing local invasion. In 2003, a revision of the classification of odontogenic tumors was advanced by Reichart and Philipsen, in which the clear cell odontogenic tumor was identified as a carcinoma. In 2005, CCOC was reclassified by the WHO as a tumor of low grade malignancy, characterized by locally destructive and aggressive behavior with local recurrence, regional lymph node metastasis, and rare distant metastasis [ , ].

Although a long time has passed since its first description, there is still much to discover about this type of tumor. Epidemiology, differentiation aspects, predictive factors and treatment outcomes are yet a topic of debate.

Here, we report a case of a maxillary clear cell odontogenic carcinoma affecting a 41-year-old male.

Case report

A 41-year-old man presented to the Department of Oral and Maxillofacial Surgery at Gemelli University Hospital with a 12-month history of a painless and gradually growing lesion of the attached gingiva of the dental element 5. The patient had been previously assessed by a general dentist who referred the patient to a specialist, for a second opinion. A complete history was taken and the examination was performed.

There was no significant past medical, surgical or dental history.

The extra-oral examination showed no anomalies. The intraoral examination revealed an alteration of the attached gingiva of the region of the elements 5 and 6 with pseudo-nodular swelling. The overlying alveolar mucosa was normal. The involved teeth were sound, positive at cold sensitivity test and without mobility. No swollen cervical lymph nodes were found, and the remainder of the physical examination was within normal limits.

A computed tomography scan without administration of contrast revealed: “presence of an erosive area of the cortical and trabecular bone located in correspondence of the upper right hemiarch, in the interdental space between dental elements 5 and 6. The aforementioned area, 14 mm in size CC x 6.6 RL, x 4 AP, causes evident erosion of the maxillary superficial cortical profile and disappearance of the trabecular design in the interdental space. There are no changes in the deep cortical profile of the maxillary bone. There is no involvement of the roots of the aforementioned dental elements, which however are in continuity with the erosive area” ( Fig. 1 ).

Fig. 1
Head CT without contrast performed before surgery showed the presence of an erosive area of the cortical and trabecular bone located in correspondence of the upper right hemiarch, in the interdental space between 1.3 and 1.4.

Based on the clinical and radiographic findings a preventive histological diagnosis was considered for treatment planning.

An incisional biopsy was performed under local anesthesia and revealed the presence of a CCOC.

A surgical resection followed by reconstruction with local flaps was planned.

The patient was admitted to the hospital for intra-oral excision of the tumor under general anesthesia.

An oscillating saw was used to perform a partial maxillectomy involving the antral floor, the alveolar bone, and teeth 4 to 6, allowing a complete en bloc resection of the tumor.

The buccal fat pad was harvested and moved to repair the oroantral communication.

The excised tumor was sent for histopathological examination.

On macroscopic examination, the tumor mass was of 1.6 cm in maximum diameter, with infiltration the maxillary bone.

The neoplasm was arranged in small nests, trabeculae and strands connected to the superficial mucosal epithelium and composed of epithelial cells with pale eosinophilic to clear cytoplasm, well demarcated cell membranes and oval to round dark nuclei, with mild nuclear pleomorphism and scarce mitotic figures. Clear cell cytoplasm contained diastase-sensitive PAS-positive material indicative of glycogen. Peripheral cells showed sometimes a partial palisading with reversed nuclear polarity, giving to the neoplasm a biphasic pattern ( Fig. 2 ).

Fig. 2
Clear cell odontogenic carcinoma (Haematoxilin and eosin, original magnification 200×).

Immunohistochemical analyses revealed positive staining for CK 5/6, p63, CK14 and negative for BER-EP4, SMA, calretinin and S100. The index of proliferation (ki67) was about 10–12%. Based on these findings, the lesion was diagnosed as a CCOC ( Fig. 3 ).

Fig. 3
Clear cell odontogenic carcinoma (Haematoxylin and eosin; A . original magnification 20×, B . original magnification 100×). C . Cytoplasm of neoplastic cells was positive for PAS. (Pas stain, original magnification 100×). Neoplastic cells showed immunoreactivity for CK5/6 ( D ), for CK14 ( E ) and for p63 ( F ). (Haematoxylin counterstaining, original magnification 100×).

Healing was uneventful without any complications and follow-up was performed at 3, 6, and 12 months.

  • 12

    months after the surgery, clinical examination and radiographs showed good healing of both of the bone and the soft tissues with no local recurrence ( Fig. 4 ).

    Fig. 4
    Clinical aspect before (a) surgical resection and after (b).


To the best of our knowledge, 107 cases of CCOC have been reported (excluding the present one) in the English literature to date. CCOC occurs most often in the fifth decade of life, with a range that goes from 14 to 89 years. Middle-aged women seem to be involved more often than the male counterparts. There seems to be no ethnicity predilection. In the current literature, no cases of Italian patients affected by CCOC are reported. The posterior mandible is the most frequently involved site, followed by the anterior mandible, maxilla and palate [ , ].

CCOC often presents itself as an asymptomatic, painless and slow-growing lesion, according to Loyola et al. [ ] and the average dimensions at diagnosis is 4 cm in diameter.

The onset of pain and tooth mobility is common and occurs approximately in one-third of patients, whereas bleeding, paresthesia, and non-healing ulcerations are less commonly reported.

The diagnosis is often late due to these deceptive and misleading signs, the duration of symptoms prior to diagnosis is reported to be of 47.62–91.9 months with a range of 1–504 months, which is uncommonly long for a malignancy [ ].

In our case, the patient was a 41- year old male presenting a 12-month history of a painless and gradually increasing lesion of the attached gingiva of the 5 region.

Radiological aspects are unspecific and poorly defined. Radiographically, CCOC is similar to other osteolytic jaw lesions and there are no typical radiographic features, X-ray images are almost always radiolucent with irregular margins; other common features are multiple cortical perforations, root resorption and in some cases, soft-tissue invasion is also noted. A minority of cases exhibit a mixed radiolucent–radiopaque lesion [ ].

The differential diagnosis of CCOC is a challenge, it comprises odontogenic and non-odontogenic tumors with clear cell changes [ ], like acinic cell carcinoma, myoepithelial carcinoma, 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 and amelanotic melanoma, metastatic tumors from kidney, thyroid, and prostate. ( Table 1 ) [ ].

Jun 12, 2021 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Clear cell odontogenic carcinoma: A case report and literature review
Premium Wordpress Themes by UFO Themes