Etiology of congenital melanocytic nevi and related conditions

Abstract

Large and giant congenital melanocytic nevi (CMN) are the rarest types of a proliferative malformation affecting the pigment cells of the skin. The phenotypic presentation is highly variable, and few reports of familial transmission exist. Current models favor a somatic mutational event occurring during at or after the end of the first trimester of gestation, within the melanocyte precursor lineage, in a predisposing genetic background. The effect of potentially implicated signaling molecules on progenitor neural crest and derivative melanocyte development is discussed. Candidates include effectors such as NRAS and BRAF of the MAP kinase pathway but also other pathways that converge on transcription factors critical for either multipotent precursor maintenance or melanocyte differentiation and which may predispose cells to inappropriate proliferation in the central nervous system or at other sites. These associated proliferations can lead in a patient-dependent manner to a clinically favorable or fatal outcome. Continued exploration of the molecular bases of large and giant CMN development will lead to new tools for more accurate prognoses in both isolated and syndromic forms.