Melanocytic nevi excised during B-Raf proto-oncogene (BRAF) inhibitor therapy: A study of 19 lesions from 10 patients

Abstract

Background: There are limited descriptions of histopathology and immune profiles of new or changing melanocytic nevi in the setting of B-Raf proto-oncogene (BRAF) inhibitor therapy.

Objective: We sought to identify their distinctive features.

Methods: Clinical charts and histologic review, neuroblastoma RAS viral (v-ras) oncogene homolog genotyping, and immunohistochemistry for HMB-45, BRAFV600E, phosphorylated extracellular signal-regulated kinase (pERK), phosphorylated protein kinase B, CD4, and CD8 were performed on 19 melanocytic nevi from 10 patients and 23 control nevi.

Results: BRAF inhibitors were administered for metastatic melanoma (7), colonic adenocarcinoma (2), and papillary thyroid carcinoma (1). The average duration of BRAF inhibition before lesion excision was 8 months. Frequently associated histologic features included pigmentation of the stratum corneum, hyperpigmented keratinocytes, dermal melanophages, and deep HMB-45 expression. The lesions were BRAFV600E and neuroblastoma RAS viral (v-ras) oncogene homolog wild-type, expressed diffuse weak-moderate pERK, and possessed a predominance of CD8(+) in comparison with CD4(+) T lymphocytes within the dermal infiltrates.

Limitation: This is a retrospective study of a small and heterogeneous group.

Conclusion: The nevi associated with BRAF inhibitor therapy invariably lack BRAFV600E mutation. BRAF inhibition appears to cause an increased cytotoxic T-cell response and increased mitogen-activated protein kinase activity in BRAF wild-type lesions, supported by pERK expression, possibly resulting in an activated phenotype characterized by increased melanin pigmentation and deep HMB-45 expression.

Keywords: B-Raf proto-oncogene inhibition; CD4; CD8; melanocytic nevi; phosphorylated extracellular signal-regulated kinase; phosphorylated protein kinase B.