Histopathologic characteristics of therapy-associated cutaneous neoplasms with vemurafenib, a selective BRAF kinase inhibitor, used in the treatment of melanoma

J Cutan Pathol. 2014 Jul;41(7):568-75. doi: 10.1111/cup.12346. Epub 2014 Apr 29.

Abstract

Background: Activating mutations in BRAF have been observed in up to 60% of melanomas, indicating a pivotal role for kinase deregulation in tumor progression. Vemurafenib is a specific inhibitor of BRAF for treatment of melanomas with activating BRAF V600E mutations and has been a major advancement in melanoma treatment. Treatment with vemurafenib, and to a lesser extent, sorafenib, a relatively non-specific inhibitor of BRAF, has been associated with cutaneous squamous cell carcinoma (SCC).

Methods: Clinical and microscopic characteristics of cutaneous neoplasms were evaluated following vemurafenib administration.

Results: Twenty-four of 47 (51%) patients receiving vemurafenib at our institution developed 146 total cutaneous neoplasms, with 75% developing multiple lesions. The median number of lesions in affected patients was three. Body distribution included head/neck (29%), chest/back (21%), upper (23%) and lower extremities (27%). Lesions were biopsied and pathologically showed multiple types of epidermal tumors including, but not limited to, verrucous keratoses with/without partial thickness dysplasia, actinic keratoses and well-differentiated and invasive SCCs with/without keratoacanthomatous features.

Conclusions: We describe the histopathologic findings of skin lesions potentially associated with vemurafenib. Additional investigation is necessary to further elucidate cutaneous neoplasms associated with vemurafenib; however, frequent dermatologic evaluation is warranted in all patients receiving BRAF inhibitors.

Keywords: BRAF inhibitor; keratoacanthoma; melanoma; squamous cell carcinoma; vemurafenib.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Humans
  • Indoles / administration & dosage
  • Indoles / adverse effects*
  • Keratoacanthoma / chemically induced*
  • Keratoacanthoma / enzymology
  • Keratoacanthoma / genetics
  • Keratoacanthoma / pathology*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / enzymology
  • Melanoma / genetics
  • Middle Aged
  • Mutation
  • Neoplasms, Second Primary / enzymology
  • Neoplasms, Second Primary / genetics
  • Neoplasms, Second Primary / pathology*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology*
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects*
  • Vemurafenib

Substances

  • Indoles
  • Sulfonamides
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf