Abstract
BACKGROUND: Clear cell neoplasms are a heterogeneous group of benign and malignant tumours characterized by the presence of clear cells on histological examination. Although uncommon in the head and neck, a wide range of intraoral tumours of varied cellular origins may exhibit clear cell changes. While distinctive histomorphological features often allow accurate diagnosis, extensive clear cell alterations with overlapping patterns can pose significant diagnostic challenges. This paper highlights such challenges and the systematic approach undertaken to establish the final diagnosis. METHODS: We report a rare case of the clear cell variant of oral squamous cell carcinoma (CCSCC) involving the maxillary alveolus in a 58-year-old female. Clinically and histologically, the lesion mimicked odontogenic tumours, salivary gland neoplasms, melanoma, and metastatic lesions of the jaws. Detailed histomorphological assessment, supported by special stains and immunohistochemistry, was performed to reach a definitive diagnosis. RESULTS: Histopathology revealed epithelial islands of clear cells with features overlapping those of salivary gland and odontogenic tumours, as well as melanoma. Special stains excluded mucoepidermoid carcinoma, calcifying epithelial odontogenic tumour, and metastatic renal cell carcinoma. Immunohistochemistry demonstrated positivity for CK19, EMA and pan-Cytokeratin, with negativity for HMB-45, S100, P63, calretinin & CK10. Examination of deeper sections showed severe epithelial dysplasia with stromal invasion, confirming the diagnosis of CCSCC. CONCLUSION: CCSCC of the oral cavity is an exceptionally rare and diagnostically challenging entity. Accurate diagnosis requires correlation of clinical, imaging, histopathology, and immunohistochemistry. Early recognition is essential, given its aggressive clinical behaviour.