Malignant cutaneous clear cell tumours: a review of histological, immunohistochemical and molecular features

Abstract

Malignant cutaneous clear cell tumors encompass a diverse range of rare skin neoplasms characterized by clear cell morphology, which can be of epidermal, adnexal, mesenchymal, or melanocytic origin. Cutaneous clear cell squamous cell carcinoma (cccSCC) is a variant of squamous cell carcinoma marked by intracellular glycogen accumulation, clear cell differentiation, and a clinical presentation similar to conventional cSCC. Trichilemmal carcinoma (TC) is a malignant adnexal tumor with outer root sheath differentiation, often mimicking cccSCC histologically, but distinguished by trichilemmal keratinization and different immunohistochemical markers. Adnexal clear cell carcinoma with comedonecrosis (ACCCC) is an aggressive, rare tumor marked by distinctive zonal architecture and central comedonecrosis. Clear cell porocarcinoma (CCP) and clear cell hidroadenocarcinoma (CCH) are adnexal malignancies originating from eccrine glands and can be differentiated by their ductal differentiation and immunohistochemistry profiles. Clear cell atypical fibroxanthoma (ccAFX) is a rare variant of AFX with pleomorphic, clear cell morphology and overlapping features with other cutaneous clear cell malignancies, requiring differentiation based on cytokeratin expression and other histological markers. Malignant PEComa and clear cell sarcoma, while rare in the skin, exhibit clear cell morphology with melanocytic differentiation and have distinct molecular profiles that aid in their diagnosis. Lastly, clear cell melanoma, considered analogous to balloon cell melanoma, is a rare histological variant of melanoma characterized by its clear, glycogen-laden cells, sharing molecular features with conventional melanoma but requiring differentiation from other clear cell tumors, using ancillary studies including immunohistochemistry. Proper histopathological analysis, aided by immunohistochemical and molecular markers, is critical for distinguishing these rare malignancies and guiding appropriate treatment.