Atypical fibroxanthoma, pleomorphic dermal sarcoma, and undifferentiated sarcoma: Updates on diagnosis, management,...

Atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma (PDS), and undifferentiated sarcoma, pleomorphic subtype (US) are rare malignant neoplasms of mesenchymal origin with many shared clinicopathologic features. AFX are usually superficial at time of diagnosis with low risk for recurrence or metastasis following surgical extirpation. In contrast, PDS and US display greater adverse histopathological features and subcutaneous invasion which portend higher risk for local recurrence, metastasis, and death. AFX and PDS form a biological spectrum defined by shared ultraviolet (UV)-signature mutations and arise on sun-exposed skin. Malignant fibrous histiocytoma (MFH), later termed undifferentiated pleomorphic sarcoma (UPS), has been repeatedly reclassified since the 1960s, leading to ambiguity in the literature. Although histopathology may overlap with AFX and PDS, US (former MFH/UPS) lacks UV-associated mutations, shows a complex karyotype, occurs on sun-protected areas, and is a diagnosis of exclusion once lineage-defined sarcomas are ruled out by ancillary studies. Due to the rarity of these tumors, definitive diagnostic, management, and surveillance guidelines have not been established. Multidisciplinary teams are recommended in more advanced cases. For unresectable, recurrent, or metastatic disease, adjunctive therapies including radiation, chemotherapeutics, and immunotherapies have been utilized with varying efficacy.