149 Histologic, immunohistochemical, and molecular features of melanocytic BAP1-mutated atypical intradermal tumors (MBAIT)

Abstract

Germline BAP1 mutations predispose patients to cutaneous and uveal melanoma, mesothelioma, kidney cancer, and basal cell carcinoma. Patients with BAP1 cancer predisposition syndrome often develop melanocytic BAP1-mutated atypical intradermal tumors (MBAITs) starting at a young age, which resemble atypical Spitz tumors histologically and are characterized by loss of BAP1 protein. Conservative re-excision is often recommended for these lesions, but their malignant potential remains uncertain. This study investigates the clinical, histologic, immunohistochemical and molecular features of 10 MBAITs. Study cases were collected from three patients who ranged in age from 7 to 34. Lesions were biopsied from the head and neck (N=7, 70%), upper extremities (N=2, 20%), and back (N=1, 10%). The percentage of melanocytes demonstrating loss of BAP1 nuclear expression ranged from 50-100% with 7 cases demonstrating more prominent loss of BAP1 expression in the deeper aspect of the lesion. The percentage of melanocytes expressing p16 ranged from 25% to 100%. Ki-67 nuclear positivity was 5% or less. There was loss of HMB45 expression in melanocytes with increasing dermal depth in 2 cases (immunostain not performed in 8 cases). FISH analysis for one MBAIT detected signals within normal limits for RREB1, cMYC, CDKN2A, and CCND1. In conclusion, MBAIT tumors demonstrate a reassuring immunohistochemical phenotype in the majority of cases including low-Ki67 positivity, loss of HMB45 expression with increasing dermal depth, and retention of p16 expression in a subset of the lesional cells. FISH analysis was also reassuring in 1 case. Further reassuring is that none of the lesions demonstrated local recurrence or distant metastasis with 9 of 10 lesions having at least 1 year follow-up. Whole exome sequencing is currently being performed for the MBAITs in this study to determine if they harbor genetic alterations that may suggest more aggressive behavior.