Hybrid granular cell tumor/perineurioma: a report of two rare cases with PIK3CA mutations

Hybrid peripheral nerve sheath tumors (PNSTs) are rare mesenchymal neoplasms with dual differentiation, most often combining two of the three main PNST types: schwannoma, neurofibroma, and perineurioma. Recognized by the WHO since 2013, these tumors can also exhibit fewer common combinations, such as hybrid granular cell tumor/perineurioma. We herein report two rare cases of hybrid granular cell tumor perineurioma with molecular analysis. Both tumors presented as dermal to subcutaneous, well-circumscribed lesions composed of a combination of spindled and granular cell components. By immunohistochemistry, the granular cells were positive for S100, SOX10, and CD68, while the perineurial cells were highlighted by EMA and GLUT1 stains. Subsequent molecular testing revealed pathogenic mutations involving PIK3CA in both cases. Our study expands on the clinical and pathologic spectrum and provides the first molecular data on these unusual neoplasms. Further, we provide a comprehensive review of the literature of all previously reported cases and briefly discuss relevant differential diagnoses and their molecular features.