Introduction: The atypical fibroxanthoma (AFX) is considered by most authorities to represent a superficial or minimally invasive variant of malignant fibrous histiocytoma that most often presents as a solitary nodule on the sun-exposed skin of the elderly. Among the rarest variants is the clear cell AFX, a lesion which raises consideration to a differential diagnosis encompassing a variety of neoplastic and non-neoplastic clear cell proliferations.
Methods: We describe three cases of a distinctive cutaneous neoplasm arising in the sun-exposed skin of elderly patients. In all cases, formalin-fixed, paraffin-embedded tissue was available for analysis. The histology in concert with the immunophenotype was held to be diagnostic of the clear cell variant of AFX.
Results: All tumors comprised sheets of large cells with foamy cytoplasms and hyperchromatic, polyploid nuclei manifesting frequent and atypical mitoses. The critical cells in our cases expressed CD68 but none of CD3, CD20, CD34, S-100 protein, muscle-specific actin, factor XIIIa, Melan-A, carcinoembryonic antigen, or cytokeratin.
Conclusion: Although typical examples of AFX provoke diagnostic consideration of spindle cell cancers of the skin (most often spindle cell melanoma, spindle cell squamous cell carcinoma, and leiomyosarcoma), the clear cell variant raises other differential diagnostic considerations instead. These include balloon cell melanoma, sebaceous carcinoma, pleomorphic liposarcoma, chordoma, parachordoma, tricholemmal carcinoma and clear cell squamous cell carcinoma. A diagnosis of AFX is one of exclusion; one must employ immunohistochemical markers to rule out the aforementioned differential diagnostic considerations. By reporting the fifth, sixth and seventh cases of clear cell AFX, we hope to alert dermatopathologists to this distinctive and unusual neoplasm, recognition of which is essential to avoid under- or over-diagnosis and inappropriate therapy.