Neurothekeoma Versus Melanoma

The clinicopathologic spectrum of neurothekeoma was elaborated upon relatively recently. As our understanding of its morphologic variability expands, so too does its differential diagnosis. Effective dissection of the differential diagnosis requires recognition of both the classic and variant morphologies, a challenging feat in itself. The remarkable morphologic plasticity exhibited by this peculiar neoplasm lends itself to confusion with various benign and malignant melanocytic and non-melanocytic neoplasms. The collision of neurothekeoma with the notoriously protean melanoma culminates in a perfect storm of diagnostic havoc. Further complicating the diagnosis is a lack of a specific immunoprofile for neurothekeoma, reflecting its uncertain origin and differentiation. Fortunately, the presence or absence of expression of certain markers, such as S100 protein, serves as an invaluable discriminatory tool. As no confirmatory molecular test has surfaced for neurothekeoma, the diagnosis rests on the integration of clinical, histopathologic, and immunohistochemical findings, which are subject to change over time as our understanding of this tumor evolves.