The neoplastic development of malignant melanoma. A biological rationale

It is suggested that melanocytes may be characterized by a differentiation pathway with four distinct stages during normal tissue maintenance: the nerve-sheath precursor stage, the dermal migratory stage, the junctional migratory stage, and the dendritic stage. Carcinogenic action on cells in these four stages may produce four classes of lesions: neurotropic melanoma, invasive malignant melanoma, epidermal melanocytic precursors of invasive malignant melanoma, and isolated atypical epidermal melanocytes. Morphologic variations within a class are interpretable as reflecting varying degrees of aberration from the behavior of normal cells in the corresponding stage. This theory accounts for morphologic variations and salient clinicopathologic correlations during the neoplastic development of malignant melanoma. It is consistent with fundamental principles of carcinogenesis, modern ideas about stem cells and differentiation, and current understanding of the pathogenesis of metastasis. It may be of some value in resolving present controversies and may contribute to the development of improved methods of diagnosis and management of malignant melanoma. Further study is necessary before these concepts may be prudently applied in clinical practice.