The melanocytic differentiation pathway in congenital melanocytic nevi: theoretical considerations

It is suggested that the melanocytic series is characterized by a differentiation pathway (MDP) that has four discrete stages during normal development and in postnatal tissue maintenance--nerve sheath precursor (nsp), dermal migratory, junctional migratory, and dendritic--and that congenital melanocytic nevi (CMN) derive from cells in the nsp stage of the MDP. This concept accounts satisfactorily for morphologic variations and clinicopathologic correlations in CMN. It also permits a unified explication of both similarities and differences between congenital and acquired melanocytic nevi (AMN), which are thought to arise by transformation of nsp cells in the MDP during postnatal tissue maintenance. This perspective suggests that answers to many basic questions about CMN may require meticulous study of the interrelations of CMN with peripheral nerve elements. Such research may be necessary to resolve current controversies about optimal criteria for distinguishing small CMN from AMN, thereby permitting an accurate assessment of the risk of malignant melanoma in association with small CMN.