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.

• Authors: Mark C Mochel, Marc R Hammond, Dennie T Frederick, Maria B Alora-Palli, Adriano Piris, Keith T Flaherty, Mai P Hoang
• Journal: Journal of the American Academy of Dermatology (J Am Acad Dermatol) Vol. 73 Issue 3 Pg. 491-9.e2 (Sep 2015) ISSN: 1097-6787 [Electronic] United States
• PMID: 26190239 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• MAS1 protein, human
• Proto-Oncogene Mas
• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Adult
• Aged
• Biopsy, Needle
• Case-Control Studies
• Combined Modality Therapy
• Female
• Follow-Up Studies
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Mohs Surgery (methods)
• Molecular Targeted Therapy (methods)
• Mutation
• Nevus, Pigmented (drug therapy, genetics, surgery)
• Proto-Oncogene Mas
• Proto-Oncogene Proteins B-raf (drug effects, genetics)
• Proto-Oncogenes (drug effects, genetics)
• Retrospective Studies
• Risk Assessment
• Skin Neoplasms (drug therapy, genetics, surgery)
• Treatment Outcome