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Case Reports

Abstract

Hybrid peripheral nerve sheath tumors (hPNSTs) are benign neoplasms that often arise in the dermis or subcutis and are commonly associated with gene fusions, most notably VGLL3. Diagnosis requires at least two nerve sheath components (schwannoma, perineurioma, or neurofibroma) but there is increasing recognition of unusual morphologic features that may correlate with alternative gene fusion partners. We present a case of a sporadic hybrid schwannoma-perineurioma with an SRF::RELA fusion in a 24-year-old female who presented with a subcutaneous hand mass. Histologically, this was an infiltrative neoplasm with a triphasic appearance including schwannian cells, slender whorled perineurial cells and fascicles of myofibroblastic cells with oval nuclei and pale eosinophilic cytoplasm resembling those seen in cellular myofibroma. There was mild nuclear atypia and scant mitotic figures. The schwannian cells were positive for S100 and SOX10, perineurial cells were highlighted by EMA, the myoid component was strongly positive for SMA and smooth muscle myosin and negative for desmin and caldesmon. The unusual phenotype prompted molecular genetic analysis via NGS, which revealed an SRF::RELA gene fusion with breakpoints similar to those reported in cellular myofibroma, explaining the findings and consistent with the established role of SRF (serum response factor) in myogenic differentiation. Only one other case of hPNST with an SRF::MYOCD fusion has been reported so far, also showing SMA expression. Together, our findings suggest that hPNSTs with an SRF fusion may represent a distinct variant. The differential diagnosis, follow up, and the molecular genetic findings will be discussed.