Plexiform Atypical Spitz Tumor With Rosette-Like Giant Cells. A Histologic and Immunohistochemical Study on a Case Suggesting Ganglioneuroblastic Differentiation. Review of the Literature and Considerations on Histogenesis

Abstract: Spitz nevi, atypical Spitz tumors and Spitzoid melanoma, the three clinicopathologic forms that constitute the spectrum of the Spitz-type melanocytic lesions, share a histologic picture characterized by large spindle and/or epithelioid ganglion-like cells, with various admixtures of multinucleate bizarre cells. This remarkable cytology has always been interpreted as an unusual, as well as unexplained form of atypia. We report a case of atypical Spitz tumor with Homer Wright–like rosettes, a feature characteristic of ganglioneuroblastic proliferation. Furthermore, the ganglion-like cells of the tumor showed basophilic punctuation in the cytoplasm, reminiscent of Nissl substance, and a few cells, whether spindled or epithelioid, were positive to neuron-specific enolase and glial fibrillary acid protein. Based on our findings, we hypothesize that the outstanding similarity of the ganglion-like cells of Spitz tumors to the normal parasympathetic ganglion cells and to the cells of ganglioneuroma and ganglioneuroblastoma may not be fortuitous. Instead, it may represent the expression of a specific pattern of melanocytic differentiation, analogous to the neurotization of common and cellular blue nevi, although in this case, it would privilege the parasympathetic lineage over the Schwannian, perineural, or endoneural pathway. Our hypothesis is supported by the literature reports of rosette formation and frank ganglioneuroblastic differentiation in Spitz tumors and melanoma and by the demonstration that parasympathetic neurons take origin from the same tracts of the neural crest as other neural and melanocytic cells. Correspondence: Elena Castelli, MD, Department of Biomedicine, Internal Medicine and Specialized Medicine (DIBIMIS), Section Dermatology, University of Palermo, AOUP Paolo Giaccone, Via del Vespro 131, 90127 Palermo, Italy (e-mail: elena.castelli@unipa.it). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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