Divergent differentiation in malignant melanomas: a review.

The aim of this review was to document and discuss diagnostic problems associated with divergent differentiation ('metaplastic change') in malignant melanomas, defined as the development in these tumours of morphologically, immunohistochemically and/or ultrastructurally recognizable non-melanocytic cell or tissue components. Types of divergent differentiation reported in malignant melanoma include: fibroblastic/myofibroblastic, Schwannian and perineurial, smooth muscle, rhabdomyosarcomatous, osteocartilaginous, ganglionic and ganglioneuroblastic, neuroendocrine and probable epithelial. Divergent differentiation is certainly a rare phenomenon and, when it occurs, can be missed by unwary pathologists and lead to diagnostic uncertainty. A carefully chosen immunohistochemical panel and the input of electron microscopy can help to clarify the nature of the cellular differentiation of these tumours and lead to a correct final diagnosis. The clinical significance of such aberrations is uncertain, nor are the underlying mechanisms as yet well defined.