BRAF wild-type melanoma in situ arising in a BRAF V600E mutant dysplastic nevus.

IMPORTANCE: The BRAF V600E mutation accounts for the majority of BRAF mutations found in cutaneous melanoma and is also commonly found in nevi. We used dermoscopy-targeted sampling and a microbiopsy device coupled with DNA sequence analysis to highlight BRAF V600E heterogeneity within a multicomponent melanocytic proliferation. This sampling technique demonstrates the prospect of in vivo application in a clinical setting.

OBSERVATIONS: A man in his 50s with Fitzpatrick skin type II presented with an irregularly pigmented melanocytic lesion on his back that met melanoma-specific dermoscopic criteria, and diagnostic shave excision of the lesion was performed. Histopathologic analysis revealed a melanoma in situ arising in a dysplastic nevus. Dermoscopy-targeted microbiopsy specimens were taken across the lesion, and genotyping was carried out on extracted DNA samples for BRAF and NRAS mutations. The melanoma in situ showed only BRAF wild-type results, while the dysplastic nevus showed both BRAF wild-type and BRAF V600E mutations. Sequencing in all DNA samples revealed NRAS wild-type genotype.

CONCLUSIONS AND RELEVANCE: Dermoscopy-targeted sampling and genotyping of a melanoma in situ arising in a dysplastic nevus revealed a phenotype-genotype paradox that confounds the exclusive significance of BRAF and NRAS mutations in melanoma pathogenesis. Further studies are required to investigate the importance of other candidate genes linked to melanomagenesis.