title: 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.
  
  
  CONCLUSIONS
  This is a retrospective study of a small and heterogeneous group.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Mochel
authors.affiliation: Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Hammond
authors.affiliation: Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Dennie T
authors.initials: DT
authors.lastname: Frederick
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Alora-Palli
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Adriano
authors.initials: A
authors.lastname: Piris
authors.affiliation: Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address: mhoang@mgh.harvard.edu.
authors.forename: Mai P
authors.initials: MP
authors.lastname: Hoang
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015580:Mohs Surgery / Q000379:methods; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D009508:Nevus, Pigmented / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery*; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000187:drug effects* / Q000235:genetics; D011519:Proto-Oncogenes / Q000187:drug effects / Q000235:genetics; D012189:Retrospective Studies; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: B-Raf proto-oncogene inhibition; CD4; CD8; melanocytic nevi; phosphorylated extracellular signal-regulated kinase; phosphorylated protein kinase B