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

Publication date: Available online 11 April 2018
Source:Journal of the American Academy of Dermatology
Author(s): Maija Kiuru, Danielle M. Tartar, Lihong Qi, Danyang Chen, Lan Yu, Thomas Konia, John D. McPherson, William J. Murphy, Maxwell A. Fung
BackgroundA subset of melanomas carrying a BRAF V600E mutation, the most common targetable mutation in melanoma, arises in association with a melanocytic nevus also harboring a BRAF V600E mutation. The detailed histomorphologic characteristics of BRAF V600E–positive nevi are not systematically documented.ObjectiveTo identify histomorphologic features correlating with BRAF V600E status in nevi.MethodsWe retrospectively identified melanocytic nevi from our laboratory reporting system. We performed a histomorphologic analysis and BRAF V600E expression analysis by immunohistochemistry.ResultsThirteen (14.8%) nevi were wild type (WT) and 76 (86.4%) positive for BRAF V600E. BRAF V600E nevi were predominantly dermal (BRAF V600E 55.3% vs. BRAF WT 15.4%, p=0.01) and showed congenital growth pattern (BRAF V600E 51.3% vs. BRAF WT 15.4%, p=0.02). BRAF V600E nevi often exhibited predominantly nested intraepidermal melanocytes, larger junctional nests, abrupt lateral circumscription, and larger cell size. Architectural disorder and inflammatory infiltrates were more often seen in BRAF WT nevi. BRAF sequencing of a subset of nevi confirmed immunohistochemical results.LimitationsLimitations include retrospective design and a small sample size of BRAF WT nevi.ConclusionsBRAF V600E is associated with distinct histomorphologic features in nevi. This may contribute to improving the accuracy of classification and diagnosis of melanocytic neoplasms.

Teaser

BRAF V600E mutation is a common genetic driver of melanocytic nevi and melanoma. BRAF V600E is associated with distinct histomorphologic features in melanocytic nevi, including dermal and congenital growth patterns. Understanding the genetic-morphologic correlates in melanocytic nevi may facilitate a more accurate classification and improved diagnosis of melanocytic neoplasms.