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The ability to predict chromosomal abnormalities with immunohistochemistry (IHC) could help select cases requiring chromosomal evaluation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fluorescence in situ hybridization (FISH)\u2010tested spitzoid neoplasms at our institution (2013\u20132021) were reviewed. p16, BRAF V600E, and preferentially expressed antigen in melanoma (PRAME) IHC results were correlated with FISH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 174 cases (1.9F:1M, median age 28\u2009years; range, 5\u2009months\u201374\u2009years) were included; final diagnoses: Spitz nevus (11%), atypical Spitz tumor (47%), spitzoid dysplastic nevus (9%), and spitzoid melanoma (32%). Sixty (34%) were FISH positive, most commonly with absolute 6p25 gain (<jats:italic>RREB1<\/jats:italic>\u00a0&gt;\u20092). Dermal mitotic count was the only clinicopathologic predictor of FISH. Among IHC\u2010stained cases, p16 was lost in 55 of 134 cases (41%); loss correlated with FISH positive (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.001, Fisher exact test). BRAF V600E (14\/88, 16%) and PRAME (15\/56, 27%) expression did not correlate with FISH alone (<jats:italic>p<\/jats:italic>\u00a0=\u20090.242 and <jats:italic>p<\/jats:italic>\u00a0=\u20090.359, respectively, Fisher exact test). When examined together, however, p16\u2010retained\/BRAF V600E\u2010negative lesions had low FISH\u2010positive rates (5\/37, 14%; 4\/37, 11% not counting isolated <jats:italic>MYB<\/jats:italic> loss); all other marker combinations had high rates (56%\u201375% of cases; <jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>p16\/BRAF V600E IHC predicts FISH results. \u201cLow\u2010risk\u201d lesions (p16<jats:sup>+<\/jats:sup>\/BRAF V600E<jats:sup>\u2212<\/jats:sup>) uncommonly have meaningful FISH abnormalities (11%). PRAME may have limited utility in this setting.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cup.14342","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T02:23:54Z","timestamp":1666232634000},"page":"155-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Combined utility of p16 and <scp>BRAF V600E<\/scp> in the evaluation of spitzoid tumors: Superiority to <scp>PRAME<\/scp> and correlation with <scp>FISH<\/scp>"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7645-631X","authenticated-orcid":false,"given":"John L.","family":"McAfee","sequence":"first","affiliation":[{"name":"Department of Anatomic Pathology, Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Scarborough","sequence":"additional","affiliation":[{"name":"Affiliated Dermatology  Dublin Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei Sophia","family":"Jia","sequence":"additional","affiliation":[{"name":"Quantitative Health Sciences Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Azzato","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology and Cytogenetics, Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Astbury","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology and Cytogenetics, Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shira","family":"Ronen","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleodor A.","family":"Andea","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetic Pathology and Dermatopathology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2278-5908","authenticated-orcid":false,"given":"Steven D.","family":"Billings","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0629-775X","authenticated-orcid":false,"given":"Jennifer S.","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio 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