Atypical fibroxanthoma: differential diagnosis from other sarcomatoid skin lesions

Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm that usually presents as a rapidly-growing nodule in sun-exposed sites in elderly patients. Despite its highly atypical histological appearance it is almost always associated with innocuous clinical behaviour. AFX is now generally regarded as the superficial counterpart of undifferentiated pleomorphic sarcoma (so-called malignant fibrous histiocytoma [MFH]). The former lesion is associated with an excellent prognosis in view of its small size, superficial location, and amenability to complete excision. Because a distinction between AFX and MFH requires assessment of the depth of invasion, a definitive diagnosis of AFX cannot be made on the basis of shallow biopsies. Other cutaneous tumours, including sarcomatoid squamous cell carcinoma (SCC) and spindle-cell melanoma, may have a histologic appearance that is indistinguishable from AFX on haematoxylin–eosin stained slides; immunochemical stains are therefore mandatory in the pathologic evaluation of such cases. There are no currently-known specific immunohistochemical markers (including CD10) which are diagnostic of AFX, and it remains a diagnosis of exclusion. Recent studies have highlighted the importance of other markers, such as high molecular-weight keratins (e.g., CK5/6, 34BE12, and MNF116) and p63 in the diagnosis of sarcomatoid squamous cell carcinoma; that tumour may fail to label for other keratin proteins. Recently, uncommon variants of AFX have been described that broaden its histological differential diagnosis.