{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:55:40Z","timestamp":1792418140634,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"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":["Histopathology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Primary cutaneous and mucosal melanoma shows a wide histological spectrum. The correct diagnosis depends upon the demonstration of melanocytic differentiation by recognition of an associated <jats:italic>in\u2010situ<\/jats:italic> component or immunohistochemical evidence of a melanocytic phenotype using conventional melanocytic markers, such as S\u2010100, SOX10, Melan\u2010A and HMB\u201045. Exceptionally, melanomas lose their melanocytic phenotype, at least focally, and show differentiation towards other lineages. Review of the literature shows that de\u2010 and trans\u2010differentiation in melanoma is rare but probably under\u2010recognised and under\u2010reported. These often large and frequently ulcerated tumours affect adults and show a wide anatomical distribution, including mucosal sites, although there is a predilection for sun\u2010damaged skin of the head and neck. Histologically, the tumours are biphasic and contain a pre\u2010existing conventional melanoma. The de\u2010differentiated component closely resembles atypical fibroxanthoma, both morphologically and immunohistochemically. Trans\u2010differentiated melanoma may show rhabdomyosarcomatous or spindle cell carcinomatous features. Undifferentiated melanomas are similar tumours in which the conventional melanoma component is absent. Their diagnosis depends entirely upon the clinical context and identification of a classical melanoma driver gene mutation, i.e. <jats:italic>BRAF<\/jats:italic> V600E. The diagnosis of these rare and unusual tumours is challenging, and requires thorough tumour sampling and recognition of the background of a pre\u2010existing but often focal conventional melanoma together with molecular analysis.<\/jats:p>","DOI":"10.1111\/his.14545","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T18:31:04Z","timestamp":1640629864000},"page":"135-149","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Primary de\u2010differentiated, trans\u2010differentiated and undifferentiated melanomas: overview of the clinicopathological, immunohistochemical and molecular spectrum"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4321-5250","authenticated-orcid":false,"given":"Ingrid","family":"Ferreira","sequence":"first","affiliation":[{"name":"Experimental Cancer Genetics Wellcome Sanger Institute Wellcome Genome Campus Cambridge 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