BRAFV600E mutation status of involuting and stable nevi in dabrafenib therapy with or without trametinib.
OBJECTIVE
Recent advances in targeting BRAFV600E mutations, which occur in roughly 50% of melanomas and 70% of benign nevi, have improved response rates and survival in patients with melanoma. With increased survival, the importance of other comorbidities increases and requires consideration in long-term management. This case report discusses dynamic dermoscopic nevus changes that occur during dabrafenib therapy and offers some conclusions regarding BRAF mutations and the changes.


METHODS
A man in his 30s had been monitored with whole-body dermoscopy at roughly 7-month intervals as part of a nevus surveillance study. Fourteen months after his initial visit, metastases were found, and the patient entered a clinical trial of dabrafenib with or without trametinib therapy. Continued dermoscopic monitoring for the next 12 months revealed that approximately 50% of the existing acquired melanocytic nevi involuted, while the remaining nevi did not change. Biopsy findings from 1 unchanged and 1 involuted nevus showed BRAF wild type in the unchanged nevus, BRAFV600E mutation in the involuting nevus, and no malignant histopathologic characteristics in either one.


CONCLUSIONS
Our observations indicate that a previously suggested hypothesis regarding involuting nevi in BRAF inhibitor therapy is correct: Nevi that involute while a patient is undergoing BRAF V600E inhibitor therapy possess the BRAF V600E mutation, while others that grow or remain unchanged are wild type. However larger-scale trials are required to gather conclusive data and create a more complete clinical picture.
Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia.
Phil
P
McClenahan
Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia.
Lynlee L
LL
Lin
Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia.
Jean-Marie
JM
Tan
Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia.
Ross
R
Flewell-Smith
Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia.
Helmut
H
Schaider
Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia2The University of Queensland, Institute for Molecular Biosciences, Brisbane, Queensland, Australia.
Kasturee
K
Jagirdar
Medical Oncology, Princess Alexandra Hospital, Wooloongabba, Queensland, Australia.
Victoria
V
Atkinson
The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia5IQ Pathology, Brisbane, Queensland, Australia.
Duncan
D
Lambie
Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia.
Tarl W
TW
Prow
Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia2The University of Queensland, Institute for Molecular Biosciences, Brisbane, Queensland, Australia.
Richard A
RA
Sturm
Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, Australia.
H Peter
HP
Soyer
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D046169:Dermoscopy; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D009154:Mutation; D009506:Nevus / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010091:Oximes / Q000008:administration & dosage; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D011728:Pyridones / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D007093:Imidazoles; D010091:Oximes; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib