The origin of epidermal melanocytes. Implications for the histogenesis of nevi and melanomas

Among the most venerable concepts in dermatopathology is Unna's 19th century notion of Abtropfung, ie, that melanocytes drop off from the epidermis to the dermis during the histogenesis of melanocytic tumors. Paradoxically, however, Unna's basic premise of an epidermal origin for melanocytes has been seriously questioned for over 40 years, based on experimental evidence favoring a neural crest origin for melanocytes. Recent work has strengthened the evidence for a neural crest origin of epidermal melanocytes, and it has been suggested that the concept of Abtropfung be replaced by the concept of Hochsteigerung. The concept of Hochsteigerung holds that melanocytes migrate up from the dermis into the epidermis-not only in normal development, but also during normal tissue maintenance. It now seems likely that the precursor of melanocytes, in both normal and abnormal differentiation, may not be a melanoblast (a primitive cell committed to melanocytic differentiation) but rather a pluripotential cell. Although axon-investing Schwann cells have been the traditional focus as the closest relative of the epidermal melanocyte, recent studies suggest that another nerve sheath cell, the perineural cell, might be a better candidate. These concepts have profound implications for the histogenesis of melanocytic nevi and melanomas.