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

Authors

  • Kari E. Sufficool MD,

    1. Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA
    Search for more papers by this author
  • Donna M. Hepper MD,

    1. Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA
    2. Division of Dermatology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA
    Search for more papers by this author
  • Gerald P. Linette MD, PhD,

    1. Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA
    Search for more papers by this author
  • Eva A. Hurst MD,

    1. Division of Dermatology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA
    Search for more papers by this author
  • Dongsi Lu MD,

    1. Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA
    Search for more papers by this author
  • Anne C. Lind MD,

    1. Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA
    Search for more papers by this author
  • Lynn A. Cornelius MD

    Corresponding author
    1. Division of Dermatology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA
    • Lynn A. Cornelius, MD

      Division of Dermatology, Department of Medicine, Campus Box 8123, Washington University School of Medicine, 660S. Euclid Avenue, St. Louis, MO 63110, USA

      Tel: +1 314 362 2643

      Fax: +1 314 454 5626

      e-mail: LCORNELI@DOM.wustl.edu

    Search for more papers by this author

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.

Ancillary