Dysplastic/Clark naevus in the era of molecular pathology.

Abstract

Dysplastic naevus has been a controversial entity since its first description by Clark in 1978. Despite a recent paradigm shift from the initially proposed notion that dysplastic naevus is a precursor to melanoma, its management has been increasingly more aggressive in the last decade. The latter is due to an unresolved uncertainty regarding its biological nature which necessitates further clarification. Recent molecular genetics, epigenetic and transcriptomic discoveries have revealed that a subset of dysplastic naevi exhibits a genomic profile which is intermediate between that of benign naevus and melanoma. This group of lesions often shows somatic mutations in non-V600E BRAF, NRAS and TERT and hemizygous deletion of CDKN2A gene as well as upregulation of genes involved in proliferation, cell adhesion and migration, and epidermal and follicular keratinocyte-related genes. These new genomic insights suggest that a proportion of dysplastic naevi have a greater propensity to evolve to melanoma; however, the clinical and histopathological features of this proposed intermediate category are still to be elucidated by further research.