Abstract

Soft tissue tumors harboring the novel VGLL3 gene fusions were recently described in a subset of hybrid schwannoma-perineuriomas. Herein we describe three additional cases which expand the morphologic spectrum of benign peripheral nerve sheath tumors (PNST). The first was a 29-year-old woman with a 0.5-cm scalp mass, found to have a deep dermal to subcutaneous moderately cellular spindle cell neoplasm composed of slender to more plump nuclei in a collagenous background. The second was a 7-year-old girl with a 2-cm right flank mass. The excision showed a highly cellular deep dermal and subcutaneous, monotonous proliferation with eosinophilic cytoplasm and spindle to ovoid nuclei. The third was a 30-year-old woman with a 1.3-cm right lateral neck nodule composed of fusiform cells in the dermis. By immunohistochemistry, all tumors showed diffuse positivity for S100 and SOX10. The first case showed patchy positivity for CD34 and EMA consistent with perineural differentiation, whereas the second and third cases were negative for GLUT1 and EMA. RNA sequencing (Archer FusionPlex) detected a CHD7::VGLL3 gene fusion in the first and second cases, and a MAMLD1::VGLL3 fusion in the third case. While our first case fits well with the currently published literature of hybrid schwannoma-perineurioma landscape, our second and third cases expand the morphologic spectrum of PNSTs harboring this gene fusion. The preliminary evidence suggests that the term “benign peripheral nerve sheath tumors with VGLL3 fusion” may be more appropriate, reflecting a wider histologic spectrum.

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