Abstract:

A 51-year-old non-Hispanic white male with BAP-1 pathogenic germline variant and 9-year history of multi-focal mesothelioma presented to our institution for in-patient work-up of disease progression. During full body skin examination, an asymptomatic, skin-colored, shiny, and firm 6 x 4 mm papule with peripheral blood vessels was identified. The lesion was located on his right upper back and duration of presence was unknown. A biopsy was obtained to rule out a neoplastic process. Microscopic examination revealed an intradermal melanocytic lesion composed of nests of nevoid melanocytes in the superficial dermis. A second population of epithelioid melanocytes varying in size and shape, with abundant eosinophilic cytoplasm, and arranged as single cells was present within a desmoplastic stroma. The larger melanocytes appeared to decrease in size and disperse with increasing dermal depth, consistent with maturation. The tumor and desmoplastic stroma were well circumscribed and the lesion did not involve specimen margins. Immunohistochemical stains for p16, Melan-A, and SOX-10 were positive in the dermal melanocytes; HMB-45 was negative. BAP-1 nuclear staining was preserved in lesional cells and Ki-67 proliferation index was low (<1%). To further evaluate tumor biology, TruSight Oncology 500 (TSO) assay and RNA Exome Fusion Panel were performed and revealed a pathogenic BAP1 chr3:52436624 c.2050C>T p.Gln684* variant with allele frequency of 47.0% (of 1387 reads), consistent with germline origin, and novel EHBP1::RASGRF1. CDKN2A, CDKN2B or TERT promoter variants were not detected. Recently, RASGRF1 rearrangements were detected in 3 cutaneous melanocytic neoplasms with spitzoid morphology. RASGRF1 fusions have been uncovered to be involved in lung and pancreatic adenocarcinomas and activation of RAF-MEK-ERK signaling, suggesting that these tumors could potentially be treated with BRAF and MEK inhibitors.

Financial Disclosure:
No current or relevant financial relationships exist.

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Maria Rodriguez Pena, MD