Ⅰ. INTRODUCTION

Clear cell odontogenic carcinoma (CCOC) is often considered as a rare tumor, first described by Hansen in 1985.(1) Formerly known as clear cell odontogenic tumor, a locally aggressive benign tumor in the WHO classification of 1992,(2) it was renamed CCOC and classified among malignant tumors after the revision of this classification in 2005. It is still considered a malignant tumor in the 2017 classification.(3)

CCOC is an extremely rare neoplasm. It’s described very few in the English-language literature.(4,5) Thus, it is not easy to notice such disease. Also, treatment plan and procedures are uncertain to some clinicians.

CCOC has no specific clinical and radiographic features, which make its diagnosis difficult. Histopathologically, CCOC is characterized by sheets and islands of vacuolated and clear cells(6) and by the presence of agglomerates of cells with eosinophilic cytoplasm. Long-term follow-up is suggested in the literature because of its potential for recurrence and distant metastases.(7)

This case report presents the histopathological and clinical features of clear cell odontogenic carcinoma excised from the mandible.

Ⅱ. CASE REPORT

A 53-year-old woman with good general health visited the oral and maxillofacial surgery department at the Seoul St. Mary's Hospital of Catholic University of Korea, with paresthesia on #35 area. She was taking medicine for hypertension and received hysterectomy about 3 years ago. She extracted left lower 2nd premolar (#35) about 20 years ago, so #35 was missing state.

Radiological examination showed a radiolucent mandibular lesion extending from the left 1st premolar to the left 1st molar area (Fig. 1). On cone-beam computed tomography (CBCT), the inferior alveolar nerve canal was not destroyed yet (Fig. 2).

Initially, she noticed that there was a black spot between left lower 1st and 2nd premolar gingival area. Patient gave a history of gradual increase of that point recently. However, there were no pain and swelling of the mandible.

Also, extraoral examination showed no specific findings. Based on the clinical findings, periapical cyst, was given as provisional diagnosis. So, cyst enucleation and biopsy was planned after left lower 1st premolar (#34) root canal treatment (RCT).

After 1 month, #34 RCT was done (Fig. 3), and then enucleation and biopsy was performed under local anesthesia. Irregularly shaped pale brown tissue fragments, measuring up to 1.7 x 1.0 cm, were confirmed. CCOC was diagnosed by biopsy result, so we explained to patient and made a decision to operate surgery under general anesthesia.

Enhanced magnetic resonance imaging (MRI) and enhanced computed tomography (CT) showed a round enhancing lesion at the bony defect site of the left mandibular body, lower premolar tooth. No metastatic lymph node or distant metastasis was detected.

Through an intraoral approach, marginal mandibulectomy from the left lower canine distal area to second molar mesial area was performed under general anesthesia. We tried marginal mandibulectomy and left lower 1st premolar and molar were also removed (Fig. 4). Marginal mandibulectomy was uneventful and the mass was removed and sent for histopathological examination (Fig. 5).

Macroscopic examination revealed, tumor size was 2.8×1.0 cm in size.

Microscopic examination of a biopsy specimen showed infiltrative tumor margin with no margin involvement. Lymphatic, vein, and perineural invasion also were absent. A diagnosis of CCOC was made on the basis of specific findings obtained by radiographs, MRI, and biopsy. The final staging was T2aN0M0 stage II.

On immunohistochemical staining, PAS showed glycogen positive, indicating clear cells (Fig. 6). PAS and DPAS stains confirmed the presence of glycogen in tumor cells.

Histology examination of the surgical specimen concluded with low mitotic activity (Ki-67 to 10%).

After 6 month, patient had no signs of recurrence and distant metastasis (Fig. 7).

Ⅲ. DISCUSSION

Clear cell odontogenic carcinoma was first described by Hansen et al. in 1985.(1) This neoplasm was initially thought to be devoid of malignant potential and classified as benign.(8) Subsequently, similar cases showing aggressive behavior, recurrent behavior and metastatic spread were reported and then designated as CCOC by Bang et al. in 1989.(9,10)

COCC is a rare tumor and difficult to make an exact diagnosis. Clinical and radiological signs are polymorphic. The most frequent radiologic type was radiolucent. Thus, the possibility of misdiagnosis is relatively high, and then surgeons could operate decompression or curettage prior to pathologic examination. Radiolucent lesion should be considered to be CCOC, when with jaw enlargement and teeth mobility, in order to identify and treat patients. When symptomatic, COCC presents with swelling and tooth mobility. Paresthesia is rare and the pain is inconstant. Radiographic assessments are not specific with differentiated osteolytic images, which can invade soft tissues or cause tooth resorptions.(11) Panoramic radiographs and CT scan can only direct the diagnosis towards an aggressive tumor process. MRI reveals the invasion of soft tissues.

Histopathologically, CCOC is also difficult to diagnose. In fact, some authors thought that clear cell ameloblastomas and CCOCs might represent a clinicopathological continuum of a single neoplastic entity.(12) In addition, clear cell carcinoma and CCOC are difficult, and in some cases, impossible to distinguish morphologically and immunohistochemically, despite a different cell of origin. Bilodeau et al. suggested that location is the most important distinguishing criterion for these tumors.(13)

CCOC is a rare odontogenic tumor with female predilection and peak age incidence in the 5th and 7th decade of life. The age was consistent with the demographic data of our patient. (14)

Published literature showed that the anterior portions of the jaws especially the mandible of females is most frequently affected.(8,15)

Braunshtein et al. reviewed the literature and found 27 cases of CCOC reported worldwide that showed a high rate of recurrence (50%) and metastasis (33%).(12) Kumar et al. also documented a case which metastasized to the 5th lumber vertebra and hip 3 years after the initial diagnosis, thus emphasizing the need for long-term follow up.(15) Local recurrence is a common finding and cytologic atypia appears to worsen with recurrent lesions. Furthermore, CCOC can be distinguished from the clear cell variant of calcifying epithelial odontogenic tumor because it lacks the characteristic calcification and amyloid deposition.(16)

There were no definite universal treatment protocols for CCOC in the literature because of the recurrences or metastasis. Once the tumor is diagnosed as CCOC, resection with a wide margin is the treatment of choice, because more conservative surgery inevitably results in recurrence and/or metastasis. Adjuvant radiotherapy is a rational option for tumors that have eroded the cortex.(17) Factors such as size of the lesion, soft tissue involvement, lymph node metastasis and most importantly, the presence or absence of positive surgical margins should be considered when developing the treatment strategy.(12)

Because the evolution of CCOC is accompanied by multiple recurrences and metastasis, long-term surveillance (including head, neck, and chest imaging examinations) is mandatory.(4,18) Recurrence and metastasis were reported as late as 20 years after the first intervention.(19,20,21)

Further investigations should be conducted with oncologists to precisely define the indications of radiotherapy and/or chemotherapy in patients with CCOC.(22)