Clear cell odontogenic carcinoma: case report with immunohistochemical findings adding support to the challenging diagnosis Flávia Caló Aquino Xavier, DDS, MSc, a Camila Oliveira Rodini, DDS, MSc, a Luciana Maria Pedreira Ramalho, DDS, PhD, b Viviane Almeida Sarmento, DDS, PhD, b Fabio Daumas Nunes, DDS, PhD, a and Suzana Cantanhede Orsini Machado de Sousa, DDS, PhD, a São Paulo and Bahia, Brazil UNIVERSITY OF SÃO PAULO AND FEDERAL UNIVERSITY OF BAHIA Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic tumor associated with aggressive clinical behavior, metastasis, and low survival. We report a case of CCOC affecting the mandible of a 39-year-old man. The tumor presented a biphasic pattern composed of clear cell nests intermingled with eosinophilic cells and separated by collagenous stroma. Immunoreactivity to cytokeratin (CK), specifically AE1/AE3 and CK 8, 14, 18, and 19 was found, as well as to epithelial membrane antigen (EMA). The tumor cells were negative for S100 protein, CK 13, vimentin, smooth muscle actin, laminin and type IV collagen. Low labeling indices for the proliferation markers Ki-67 and proliferating cell nuclear antigen and to p53 protein might predict a favorable prognosis for the lesion. A surgical resection was performed, followed by adjuvant radiotherapy. A 2-year follow-up has shown no signs of recurrence. The significance of histochemical and immunohistochemical resources in the correct diagnosis of CCOC is analyzed. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:403-10) Clear cell odontogenic carcinoma (CCOC) is an ex- tremely uncommon entity that was originally described in 1985 by Hansen et al. 1 as a benign but locally invasive tumor. However, owing to its behavior as an infiltrative neoplasm with a marked tendency for local recurrence, regional lymph node and possible distant, mainly pulmonary, metastasis, 2,3 the World Health Or- ganization (WHO) reclassified it in 2005 as a malignant tumor of odontogenic origin. 4 This tumor tends to oc- cur in the mandible of older adults, with a predilection for women. 5-15 A prominent histopathologic feature is the presence of islands composed of clear cells with well defined outlines and centrally placed nuclei. 16 Various differential diagnoses are considered, includ- ing squamous cell carcinoma, mucoepidermoid carci- noma, clear cell ameloblastoma, hyalinizing squamous cell carcinoma, 16 calcifying epithelial odontogenic tu- mor, and metastatic clear cell carcinoma of renal origin and metastatic melanoma. 13 Complete understanding of the behavior of CCOC remains unclear, because only 54 cases have been de- scribed since 1985. Despite the increased awareness and improved recognition of these tumors, reported treatment strategies remain diverse. Therefore, addi- tional cases and long-term follow-up could help to elucidate the tumor biology. We report a case of CCOC of the mandible, presenting the clinical and radiologic aspects, and focusing on the importance of histopatho- logic and immunohistochemical features in properly establishing its diagnosis. CASE REPORT A 39-year-old man presented for evaluation with a painful swelling of 2 months’ duration on the right side of his mandible, noticed after a tooth extraction. However, the pain had started only recently. Local physical examination showed a firm irregular lump that appeared to arise from the right mandible. In- traorally, the tumor could be seen as a 4 cm reddish, bulging, fleshy mass presenting areas of ulceration (Fig. 1, A). The remainder of the physical examina- tion was not contributory, and lymph nodes were nonpalpable. Orthopantomogram of the mandible showed a well delineated radiolucent multilocular lesion in the lower right molar area extending to the ramus, centered in and destroying a portion of the right mandibular body without cortical bone expan- sion (Fig. 1, B). A clinical diagnosis of malignant neoplasm of odontogenic origin was given. a Department of Stomatology (Oral Pathology), Dental School, Uni- versity of São Paulo, São Paulo, Brazil. b Department of Diagnostic and Therapeutic Support, Dental School, Federal University of Bahia, Bahia, Brazil. Received for publication Dec 19, 2007; returned for revision Feb 8, 2008; accepted for publication Mar 10, 2008. 1079-2104/$ - see front matter © 2008 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2008.03.010 403