We report the case of a 94-year-old man with a rapidly growing nodule on the preauricular area, which on histology showed a poorly differentiated spindle cell tumor with negative p63 and p40 antibody immunostains, negative high- and low-molecular-weight cytokeratins albeit for a focal expression of cytokeratin AE1/AE3. Spindle cell melanoma, angiosarcoma, and leiomyosarcoma were excluded. We explore the diagnostic approach to this challenging conundrum. Certain authors have suggested that sarcomatoid carcinoma and atypical fibroxanthoma (AFX) may lie within a spectrum of "sarcoma-like tumors of the head and neck" and that they may all run a similarly indolent clinical course. However, AFX appears to remain a diagnosis of exclusion, and expert consensus is that by definition AFX cannot express any cytokeratin antigens.
Keywords: atypical fibroxanthoma; dermatopathology; keratin-positive atypical fibroxanthoma; pleomorphic dermal sarcoma; sarcomatoid carcinoma; spindle cell squamous cell carcinoma.