Comprehensive Immunohistochemical Analysis of Atypical Fibroxanthoma: Focus on PRAME in Differential Diagnosis

BACKGROUND: Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm predominantly affecting elderly individuals in sun-exposed areas. Despite its alarming histopathological features, AFX typically exhibits an indolent clinical course. Diagnosis remains challenging due to overlapping features with other aggressive cutaneous malignancies, especially malignant melanoma. METHODS: We retrospectively analyzed 15 cases of AFX diagnosed between 2009 and 2024. Comprehensive immunohistochemical profiling was performed, including CD10, CD68, S100, Melan-A, HMB45, CD31, CD34, ERG, cytokeratins, P40, P63, SMA, Desmin, and newly, PRAME (clone EPR20330). Clinical and follow-up data were collected from medical records. RESULTS: The cohort had a mean age of 72.9 years, with a male predominance (66.7%). The scalp was the most frequent tumor site (40.0%). All cases demonstrated diffuse block-type CD10 positivity and were uniformly negative for PRAME. Occasional weak staining for melanocytic markers was observed in a minority of cases. After a mean follow-up of 84.0 months, all patients were alive. CONCLUSION: A comprehensive immunohistochemical panel is essential for the accurate diagnosis of AFX. The absence of PRAME expression, together with block-type CD10 positivity, supports the distinction of AFX from malignant melanoma and other histological mimics, facilitating appropriate clinical management.