Recurrent clear cell odontogenic carcinoma initially diagnosed as ameloblastoma: A case report and review of literature

Clear cell odontogenic carcinoma (CCOC) is a rare, malignant tumor primarily affecting the mandible in middle-aged women, known to be highly recurrent post-surgery. A 56-year-old female, with an initial diagnosis of ameloblastoma based on radiological findings, had her diagnosis revised to CCOC at Ghent University Hospital after histopathological analysis and EWSR1::CREB1 gene fusion confirmation. Despite undergoing a Brown-Shah IID maxillectomy, radical neck dissection, and fibula flap reconstruction, she faced a recurrence within a year, complicated by an Aspergillus fumigatus infection requiring antifungal treatments and debridements. Diagnosis relies on immunohistochemical markers p40, p63, CK5, SMA, Calponin, and S-100. Additionally, over 80 % of CCOC cases show EWSR1 gene rearrangements. Treatment includes surgical resection and fibula free flap reconstruction. Adjuvant radiotherapy may be beneficial in cases with compromised margins or positive lymph nodes. Prophylactic antifungal treatment is recommended for at-risk patients. The complex nature of CCOC requires thorough follow-up and potentially adjuvant therapies. • EWSR1::CREB1 fusion distinguishes Clear Cell Odontogenic Carcinoma from Ameloblastoma. • p40 positivity excludes RCC; SMA, S-100 negativity exclude salivary tumors. • Adjuvant radiotherapy may benefit CCOC cases with positive surgical margins. • Prophylactic antifungal therapy may prevent superinfection in at risk patients with necrotic flap tissue.