Atypical Fibroxanthoma Demonstrating HMB45+ Staining

Immunohistochemistry is useful and often necessary for the diagnosis of many histopathological entities, including atypical fibroxanthoma (AFX), which is typically considered a diagnosis of exclusion after ruling out spindle cell melanoma, sarcomatoid carcinoma, and other spindle cell tumors. AFX is a superficial fibrohistiocytic tumor previously believed to be related to pleomorphic sarcoma (formerly known as malignant fibrous histiocytoma), but is now considered a distinct clinicopathological entity. AFXs commonly express CD68, smooth muscle actin, and lysozyme and are usually negative for melanocytic markers such as HMB45 and S100. However, immunohistochemistry can sometimes be misleading, especially when used without other relevant markers in making a histopathologic diagnosis. HMB45 is a glycoprotein marker of premelanosomes and is often helpful in identifying melanoma because it stains melanosomes in the epidermis, dermis, and nevi glycocomplexes. We report a case of AFX which was strongly positive for HMB45, but negative for all other melanocytic markers. This case emphasizes the potential pitfall of relying on a single immunohistochemical marker to make the diagnosis, especially of melanoma, and also is one of the only rare reported cases of AFXs which are HMB45+.