The histogenesis of acquired melanocytic nevi. Based on a new concept of melanocytic differentiation

A new concept of melanocytic differentiation during normal development is presented, suggesting that 1) normally developing melanocytes and Wagner-Meissner bodies are both derived from primitive, pluripotential precursors in the perineural region of fetal cutaneous nerves; and 2) melanocytes, like keratinocytes and many other cell series, have a differentiation pathway with discrete stages. The proposed stages of the melanocytic differentiation pathway are: the nerve-sheath precursor stage, the dermal migratory stage, the junctional migratory stage, and the dendritic stage. This theory is consistent with current knowledge of human embryology, present understanding of the biology of cells derived from the neural crest, and modern concepts of stem cells and differentiation. Based on this concept, it is proposed that the commonly encountered types of acquired melanocytic nevi derive from pluripotential cells in the nerve-sheath precursor stage of the melanocytic differentiation pathway. As the progeny of these precursors attempt to mature along the pathway, they may produce various patterns that may be interpreted as caricatures of the stages in the pathway. In particular, maturation of most elements to the dendritic stage may produce the pattern of lentigo simplex; predominance of maturation to the junctional migratory stage may produce the pattern of junctional nevi; predominance of maturation to the dermal migratory stage may produce the pattern of intradermal nevi; and failure of progeny to mature along the melanocytic differentiation pathway may produce the pattern of neuroid nevi. This histogenetic model accounts satisfactorily for morphologic variations and clinicopathologic correlations in acquired melanocytic nevi.