title: Multiple BRAF Wild-Type Melanomas During Dabrafenib Treatment for Metastatic BRAF-Mutant Melanoma.
abstract: OBJECTIVE
  BRAF inhibitors have become the standard of care in metastatic BRAF-mutant melanomas. Compared with chemotherapies, BRAF inhibitors improve overall and disease-free survival and speed the recovery of symptomatic patients with metastatic disease. The most worrisome finding is the possible development of resistance to new malignant tumors.
  
  
  METHODS
  A patient in her 30s developed massive BRAFV600E melanoma metastasis during her 30th week of pregnancy. After emergency cesarean delivery, oral dabrafenib treatment was initiated, and a partial radiologic response was confirmed within 1 month. At dermatologic digital follow-up aided by confocal microscopy 8 weeks after initiation of dabrafenib treatment, 4 melanomas were detected. Unfortunately, within the next month, the melanoma rapidly progressed. The 4 new melanomas were wild-type BRAFmelanomas, whereas the new metastasis carried a different BRAF mutation (S467L).
  
  
  CONCLUSIONS
  Cutaneous malignant tumors are the most frequent adverse events of BRAF inhibitors; therefore, strict dermatologic surveillance in a referral center aided by digital follow-up is mandatory, especially when multiple nevi are present and these drugs are used in an adjuvant setting. In view of our findings, the pathogenesis of the development of new melanomas seems to be different from therapy resistance. Whether paradoxical RAF activation could explain these BRAF wild-type secondary malignant tumors is still unknown.
authors: Melanoma Unit, Department of Dermatology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain2Centro de Investigación Biomédica en Red en Enfermedades Raras, Instituto de Salud Carlos III, B.
authors: Cristina
authors: C
authors: Carrera
authors: Centro de Investigación Biomédica en Red en Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain3Department of Biochemical and Molecular Genetics, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barc.
authors: Joan A
authors: JA
authors: Puig-Butillè
authors: Centro de Investigación Biomédica en Red en Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain3Department of Biochemical and Molecular Genetics, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barc.
authors: Gemma
authors: G
authors: Tell-Marti
authors: Department of Pathology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors: Adriana
authors: A
authors: García
authors: Centro de Investigación Biomédica en Red en Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain3Department of Biochemical and Molecular Genetics, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barc.
authors: Celia
authors: C
authors: Badenas
authors: Department of Pathology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors: Llucia
authors: L
authors: Alós
authors: Melanoma Unit, Department of Dermatology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain2Centro de Investigación Biomédica en Red en Enfermedades Raras, Instituto de Salud Carlos III, B.
authors: Susana
authors: S
authors: Puig
authors: Melanoma Unit, Department of Dermatology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain2Centro de Investigación Biomédica en Red en Enfermedades Raras, Instituto de Salud Carlos III, B.
authors: Josep
authors: J
authors: Malvehy
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002585:Cesarean Section; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007231:Infant, Newborn; D050498:Live Birth; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D009154:Mutation; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010091:Oximes / Q000627:therapeutic use*; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib