{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:59:17Z","timestamp":1782493157560,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T00:00:00Z","timestamp":1755388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cutan Pathol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Differentiating metastatic melanoma from histologic mimics such as malignant gastrointestinal neuroectodermal tumor (GNET), malignant melanotic nerve sheath tumor (MMNST), and epithelioid malignant peripheral nerve sheath tumor (EMPNST) poses significant diagnostic challenges due to overlapping morphology and immunophenotypes. PRAME is a novel immunohistochemical marker increasingly used to distinguish melanoma from its mimics, but remains underexplored in these rare tumor types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PRAME immunohistochemistry was performed on four GNETs, seven MMNSTs, 10 EMPNSTs, 16 metastatic melanomas (including eight undifferentiated melanomas), and two MITF\u2010rearranged melanocytic tumors. PRAME expression was scored from 0 to 4+ based on the percentage of tumor nuclei showing moderate to strong staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All GNETs, MMNSTs, and MITF\u2010rearranged tumors were PRAME\u2010negative. EMPNSTs showed variable expression: six were negative (0\u20131), one equivocal (2+), and three positive (3\u20134+). Fifteen of 16 melanomas were PRAME\u2010positive. PRAME scores differed significantly among tumor types (<jats:italic>p<\/jats:italic>\u2009=\u20091.99\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>). PRAME demonstrated high sensitivity and specificity for distinguishing metastatic melanoma from primary mimickers including GNET and MMNST, but low specificity in EMPNST (71.4%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PRAME reliably distinguishes metastatic melanoma from GNET and MMNST, supporting its use in this differential. However, its reduced specificity in EMPNST limits its standalone diagnostic value in this context, emphasizing the need for a multimodal approach.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cup.14849","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T01:15:42Z","timestamp":1755479742000},"page":"710-719","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Diagnostic Utility of PRAME in Rare Melanoma Mimics: A Comparative Analysis Including GNET, MMNST, Epithelioid MPNST, and MITF\u2010Rearranged Melanocytic Tumors"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-3692","authenticated-orcid":false,"given":"Ahmed","family":"Shah","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9306-1643","authenticated-orcid":false,"given":"Jeremiah F.","family":"Molligan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5214-4813","authenticated-orcid":false,"given":"Carina A.","family":"Dehner","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Laboratory Medicine Indiana University  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Torres\u2010Mora","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota 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