Definitive Diagnosis of Angiomatoid Fibrous Histiocytoma Using Dual DNA/RNA Genomic Profiling.

Background/aim: Angiomatoid fibrous histiocytoma (AFH) is a rare soft-tissue tumor that typically occurs in young individuals and often mimics hematomas or sarcomas. Its diagnosis is difficult due to nonspecific histological features, and identification of gene fusions such as EWSR1-CREB1 is crucial. We report a case definitively diagnosed using GenMineTOP, a dual DNA/RNA genomic profiling panel.

Case Report: A 61-year-old woman presented with acute onset of pain and swelling in the right popliteal fossa, initially diagnosed as a hematoma. MRI revealed a 10-cm intramuscular mass with heterogeneous signal intensity and fluid-fluid levels. Needle biopsy showed no tumor cells. Despite transient improvement, the mass persisted and anemia worsened, prompting surgical excision. The tumor was resected with marginal margins, and histology revealed large atypical cells with unclear differentiation. Postoperative radiotherapy (60 Gy in 30 fractions) was administered under suspicion of sarcoma. GenMineTOP testing identified an EWSR1-CREB1 fusion gene. Reevaluation confirmed AFH with characteristic lymphoid cuffs and CD68 positivity. One year postoperatively, the patient remains free of recurrence and metastasis.

Conclusion: This case underscores the diagnostic challenges of AFH, particularly in older patients with deep-seated lesions mimicking hematomas. Dual DNA/RNA genomic profiling enabled definitive diagnosis and demonstrated its clinical utility in evaluating soft-tissue tumors with ambiguous histopathological features.