Diagnostic Challenge: Angiomatoid Fibrous Histiocytoma with EWSR1 Rearrangement

This image report aims to illustrate the diagnostic value of integrating various diagnostic modalities to distinguish angiomatoid fibrous histiocytoma (AFH) from malignant soft tissue tumors. A 33-year-old man presented with a painful palpable mass in the medial left thigh. Magnetic resonance imaging revealed a 27 × 23 × 20 mm intramuscular lesion in the vastus medialis with a mixed T1 signal, predominantly high T2/STIR signal, internal hyperintense foci, a capsule-like rim, septations, heterogeneous enhancement, and marked peritumoral edema extending beyond the apparent tumor margins. Because these findings raised concern for a malignant soft tissue tumor, wide excision was performed after biopsy suggestive of low-grade sarcoma. Histologically, the tumor comprised spindle to epithelioid cells arranged in fascicular and storiform patterns surrounded by a lymphoid cuff. Immunohistochemistry showed positivity for CD68, CD99, and EMA, partial desmin and S-100 expression, and a Ki-67 index of 15%. Differential diagnosis included AFH and a malignant peripheral nerve sheath tumor. FISH demonstrated EWSR1 rearrangement, while PCR testing for EWSR1-CREB1 and EWSR1-ATF1 was negative. Although the specific fusion partner could not be identified, an EWSR1 rearrangement, together with the histologic and immunohistochemical findings, was considered supportive but not definitive for AFH. AFH, a rare intermediate tumor with nonspecific imaging features and variable pathology, makes diagnosis challenging. This case emphasizes the need to consider AFH in the diagnosis of intramuscular tumors with disproportionate peritumoral edema and highlights the role of molecular analysis in confirming the diagnosis.