A Case of Hybrid Cellular Neurothekeoma and Perineurioma With a Folliculin Gene Mutation

Abstract

Hybrid peripheral nerve sheath tumors (PNSTs) are benign tumors that show features of more than one type of PNST. Benign cutaneous plexiform hybrid tumor of perineurioma and cellular neurothekeoma (BCPHTPCN) is a rare, recently described entity that shows various combinations of histomorphologic and immunophenotypic features of the PNSTs perineurioma and cellular neurothekeoma. Our case describes a middle-aged man initially presenting with an acute papulopustular rosacea flare. Rosacea treatment unmasked a prominent erythematous papule on the forehead. A biopsy was taken, and histopathological examination showed a proliferation of epithelioid, ovoid, and spindled cells arranged in a compact nested and intersecting fascicular growth. Immunohistochemical stains were positive for NKI/C3, CD10, PGP9.5, MITF, and GLUT-1. There was weak reactivity with EMA and minimal reactivity with Claudin-1. Tumor cells were negative for SOX10, CD163, CD68, CD34, ALK, and Pan-TRK. The patient was diagnosed with BCPHTPCN. DNA and RNA sequencing showed a folliculin (FLCN) gene mutation, which is most commonly associated with Birt-Hogg-Dubé syndrome. The patient underwent excision and has remained without recurrence or complications several months post-diagnosis. We hope to expand the clinical and histopathologic characteristics of this peculiar neoplasm, as well as provide additional insight that might improve our understanding of BCPHTPCN tumorigenesis.