Improving classification of melanocytic nevi: Association of BRAF V600E expression with distinct histomorphologic features.

ABSTRACT

BACKGROUND: A subset of melanomas carrying a B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E mutation, which is the most common targetable mutation in melanoma, arise in association with a melanocytic nevus that is also harboring a BRAF V600E mutation. The detailed histomorphologic characteristics of nevi positive for BRAF V600E have not been systematically documented. OBJECTIVE: To identify histomorphologic features correlating with BRAF V600E status in nevi. METHODS: We retrospectively identified melanocytic nevi from our laboratory reporting system. We performed a histomorphologic analysis and analysis of BRAF V600E expression by immunohistochemistry. RESULTS: Thirteen nevi (14.8%) were negative and 76 (86.4%) were positive for BRAF V600E. The nevi positive for BRAF V600E were predominantly dermal (predominantly dermal growth in 55.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P = .01]) and showed a congenital growth pattern (congenital growth pattern in 51.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P = .02]). Compared with nevi negative for BRAF V600E, those that were positive for BRAF V600E often exhibited predominantly nested intraepidermal melanocytes, larger junctional nests, abrupt lateral circumscription, and larger cell size. Architectural disorder and inflammatory infiltrates were seen more often in nevi negative for BRAF V600E. BRAF sequencing of a subset of nevi confirmed the immunohistochemical results. LIMITATIONS: Limitations include the study's retrospective design and the small sample size of nevi negative for BRAF V600E. CONCLUSIONS: BRAF V600E is associated with distinct histomorphologic features in nevi. These features may contribute to improving the accuracy of classification and diagnosis of melanocytic neoplasms.