Spectrum of spitzoid neoplasms: genetic aberrations and diagnostic tools reappraisal

Spitzoid melanocytic neoplasms, which consist of Spitz nevi, atypical Spitz tumors, and spitzoid melanomas, are difficult to distinguish from one another by light microscopy. Further information regarding spitzoid melanocytic neoplasms can aid in the diagnosis. The objective of this study was to review the current literature concerning spitzoid melanocytic neoplasms and present the most current perspective regarding common fusions found in spitzoid neoplasms along with common genetic diagnostic approaches. BAP1, ALK, NTRK1, NTRK3, BRAF, ROS1, and HRAS have been associated with spitzoid melanocytic neoplasms, and common histological findings, types of cancers associated with these mutations, and mechanism of action are discussed. The utility of P16 immunostain, fluorescence in-situ hybridization, and comparative genomic hybridization as ancillary tests are described, as well as how they could potentially help when evaluating a spitzoid proliferation. The spectrum of spitzoid neoplasm is large and can be difficult to navigate in diagnosis. Fortunately, there have been great advances in the understanding of specific fusions associated with spitzoid neoplasms and their histological findings. Immunohistochemical analysis and genetic testing have also greatly improved to help aid in the diagnosis of spitzoid neoplasms.