title: Second primary melanomas treated with BRAF blockers: study by reflectance confocal microscopy.
abstract: BACKGROUND
  New primary melanomas arising in patients with stage IV melanoma and receiving BRAF inhibitors have recently been reported. This raises the question of the nature of the earliest cellular events identifiable within pre-existing moles.
  
  
  OBJECTIVE
  To use reflectance confocal microscopy (RCM) to investigate changing moles in patients using vemurafenib.
  
  
  METHODS
  In the first part of the study 23 lesions were examined by RCM before excision (performed because of digital dermoscopy changes) and histopathological examination. In the second part, 10 randomly chosen lesions in two patients were examined before and after 3 months of vemurafenib treatment.
  
  
  RESULTS
  The first step permitted the highlighting of an unusual RCM pattern identified in five lesions characterized by areas of marked atypia in otherwise nondysplastic lesions. In the second step, four initially nondysplastic lesions developed focal or multifocal areas of marked atypia under treatment, which were not always correlated with digital dermoscopy changes, but did correlate with histopathology. All four lesions were finally diagnosed as melanomas.
  
  
  CONCLUSIONS
  Although the clinical relevance of such findings remains questionable, RCM allowed us to observe, at the cellular level, the earliest events occurring within vemurafenib-induced changing moles. Moreover, repeated RCM examinations permitted to confirm that microscopic marked atypia that led to the histopathological diagnosis of melanoma appeared under treatment and were not pre-existing.
authors.affiliation: Dermatology Department, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France. sebastien.debarbieux@chu-lyon.fr
authors.forename: S
authors.initials: S
authors.lastname: Debarbieux
authors.forename: S
authors.initials: S
authors.lastname: Dalle
authors.forename: L
authors.initials: L
authors.lastname: Depaepe
authors.forename: N
authors.initials: N
authors.lastname: Poulalhon
authors.forename: B
authors.initials: B
authors.lastname: Balme
authors.forename: L
authors.initials: L
authors.lastname: Thomas
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D046169:Dermoscopy; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D018613:Microscopy, Confocal / Q000379:methods; D016609:Neoplasms, Second Primary / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use*; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf