{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T09:21:01Z","timestamp":1787649661656,"version":"build-2736575974"},"reference-count":25,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Surg Pathol"],"abstract":"<jats:p>\n                    Undifferentiated\/dedifferentiated melanomas typically lack all conventional melanocytic biomarkers and closely mimic non-melanocytic malignancies, risking misclassification and missed melanoma-directed therapy. We report four metastatic undifferentiated\/dedifferentiated melanomas from 3 women and 1 man (median age 67 years) to genitourinary (GU) sites, involving the adrenal gland (n\u2009=\u20092), kidney (n\u2009=\u20091), and perirenal soft tissue (n\u2009=\u20091). Resected tumors (n\u2009=\u20093; median 5.4\u2005cm) and one biopsy specimen showed high-grade epithelioid and\/or spindle-cell morphology with brisk mitotic figures. All four tumors were S100\/SOX10\/MelanA\/HMB45 negative. PAX8 was also negative. In contrast, pan-keratin\/CAM5.2\/cytokeratin AE1\/AE3 and\/or p63 showed focal\/multifocal staining in all resected tumors. Additional pitfalls included focal weak TFE3 and scattered cathepsin K expression. PD-L1 was diffusely positive (70%-100% of tumor cells) in 2 tested tumors. Targeted next-generation sequencing showed a MAPK-pathway driver in all tumors:\n                    <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                    class-3 (D594N, G466R) in 2\/4 tumors,\n                    <jats:italic toggle=\"yes\">NRAS Q61R<\/jats:italic>\n                    in 1 tumor, and\n                    <jats:italic toggle=\"yes\">NF1<\/jats:italic>\n                    truncation (R440*) in 1 tumor, with frequent co-events (\n                    <jats:italic toggle=\"yes\">TERT<\/jats:italic>\n                    promoter mutations;\n                    <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                    loss;\n                    <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                    mutation). UV mutational signatures and high tumor mutational burden supported cutaneous origin. One patient showed clonal continuity between a prior liver metastasis and the subsequent adrenal gland lesion. All patients received PD-1-based immunotherapy (pembrolizumab n\u2009=\u20093; nivolumab n\u2009=\u20091). Three patients achieved complete responses and remain alive and disease-free (median follow-up 28 months; range, 1.8 months-10.5 years), while one patient was lost to follow-up at 2 months with progressive disease. Accurate recognition of these metastatic tumors enables effective therapy. To our knowledge, this is the first dedicated series of GU-site specific undifferentiated\/dedifferentiated melanoma and provides a framework for work-up and management.\n                  <\/jats:p>","DOI":"10.1177\/10668969261470831","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:58:33Z","timestamp":1784728713000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Undifferentiated and Dedifferentiated Melanoma of the Genitourinary Tract: A Case Series Demonstrating the Potential for Diagnostic Pitfalls"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2792-3955","authenticated-orcid":false,"given":"Federico","family":"Repetto","sequence":"first","affiliation":[{"name":"Brigham and Women's Hospital and Harvard Medical School"},{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor E.","family":"Russell-Goldman","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3732-8256","authenticated-orcid":false,"given":"Lyn","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Dias-Santagata","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Odintsov","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres M.","family":"Acosta","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Chebib","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Oliva","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0444-0068","authenticated-orcid":false,"given":"Chin-Lee","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-8564","authenticated-orcid":false,"given":"Michelle S.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"e_1_3_2_2_2","volume-title":"Skin Tumours. 5th ed. 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