Genomic Assessment of Blitz Nevi Suggests Classification as a Subset of Blue Nevus Rather Than Spitz Nevus: Clinical, Histopathologic, and Molecular Analysis of 18 Cases

Abstract: Blitz nevi/tumors are a distinct subset of melanocytic neoplasia which show mixed morphologic features of Spitz and blue nevus. Genomically, most blue nevi have GNAQ or GNA11 mutations while most Spitzoid neoplasms have either an HRAS mutation or translocations involving MET, ROS, BRAF, ALK1, NTRK1, and RET. The criteria used for the assessment of malignancy in blue and Spitzoid lesions are different, and these lesions have different prognostic markers. In this study, we assess the clinical, morphological, and genomic changes in 18 cases of Blitz nevi/tumors to better characterize this subset of neoplasms and determine their optimal genomic classification. Most lesions occurred on the extremities followed by the head and neck region typical of blue nevi. Histology showed most cases having a prominent plexiform growth pattern with cells aggregating around the adnexal structures and neurovascular bundles also typical of blue nevi. Using next generation sequencing, we detected the presence of somatic mutations in GNAQ or GNA11 in 4 of 7 cases (57%) of Blitz nevi with sufficient DNA available for sequencing. Normal skin samples in these 4 cases were sequenced to confirm that the GNAQ or GNA11 mutations were somatic mutations. All 4 cases were negative for immunohistochemical assessment for wild-type BRAF, RET, ALK, and NTRK1 and mutational analysis of HRAS was also negative in all cases. Hence, our study suggests that Blitz nevi/tumors are a distinct subset which genomically are best classified as a subset of blue nevi.

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