title: Histopathologic characteristics of therapy-associated cutaneous neoplasms with vemurafenib, a selective BRAF kinase inhibitor, used in the treatment of melanoma.
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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Kari E
authors.initials: KE
authors.lastname: Sufficool
authors.forename: Donna M
authors.initials: DM
authors.lastname: Hepper
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Linette
authors.forename: Eva A
authors.initials: EA
authors.lastname: Hurst
authors.forename: Dongsi
authors.initials: D
authors.lastname: Lu
authors.forename: Anne C
authors.initials: AC
authors.lastname: Lind
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Cornelius
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D007636:Keratoacanthoma / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF inhibitor; keratoacanthoma; melanoma; squamous cell carcinoma; vemurafenib