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Desmoplastic Melanoma, Neurotropism, and Neurotrophin Receptors—What We Know and What We Do Not

Desmoplastic melanoma (DM) is a relatively rare cytomorphologic variant of melanoma with a marked propensity for perineural invasion (PNI). Historically, DMs that display PNI have been grouped under the umbrella term of neurotropic melanoma (NM). However, definitions for NM and desmoplastic NM are not consistent in the literature, presenting a barrier to a comprehensive understanding of these lesions. In this review, we parse the literature on DM, NM, and desmoplastic NM, to clarify definitions and ascertain the incidence of PNI, with a view toward understanding its prognostic relevance. Neurotrophins, which represent a family of signaling peptides important to the development and maintenance of the peripheral nervous system, have been implicated in the pathogenesis of PNI in select lineage-unrelated malignancies. Given this, we also detail evidence linking neurotrophins and their receptors (TrkA, RET, p75NGFR, and NCAM) to the pathogenesis of PNI in melanoma.