Atypical fibroxanthoma and pleomorphic dermal sarcoma: current controversies, diagnostic boundaries, and practical pitfalls

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are ultraviolet-associated pleomorphic cutaneous sarcomas of uncertain differentiation that arise predominantly on chronically sun damaged skin of older adults. Most contemporary sources regard AFX and PDS as points along a biologically related spectrum with substantial overlap in morphology, immunophenotype, and molecular alterations, while distinguishing them operationally by adverse histologic features and depth of invasion that correlate with clinical risk. Nevertheless, diagnostic boundaries remain debated, terminology is inconsistently applied, and misclassification persists, most often because superficial sampling fails to capture the features that define PDS-level risk. Additional diagnostic complexity arises from the non-specific immunoprofile of AFX/PDS and from high-stakes mimickers, particularly dedifferentiated or undifferentiated melanoma and sarcomatoid/metaplastic carcinoma, which may show loss or focal expression of lineage markers. This review summarizes the historical evolution from malignant fibrous histiocytoma to undifferentiated pleomorphic sarcoma, outlines the current placement of AFX and PDS among cutaneous tumors of uncertain differentiation, synthesizes current debates regarding diagnostic thresholds, and proposes a practical escalation and reporting framework emphasizing specimen adequacy, clinicopathologic correlation, expanded immunohistochemistry, selective molecular testing, and explicit documentation of adverse features. Recent outcome data further support the clinical relevance of this distinction, with substantially higher recurrence and metastatic risk in PDS than in AFX.