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However, the morphology of\n                    <jats:italic>FGFR3<\/jats:italic>\n                    ::\n                    <jats:italic>TACC3<\/jats:italic>\n                    -positive head and neck carcinomas has not been well studied and it is unclear if this fusion represents a random event, or if it might characterize a morphologically distinct tumor type. We describe nine\n                    <jats:italic>FGFR3<\/jats:italic>\n                    ::\n                    <jats:italic>TACC3<\/jats:italic>\n                    fusion\u2013positive head and neck carcinomas affecting six males and three females aged 38 to 89\u00a0years (median, 59). The tumors originated in the sinonasal tract (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094), parotid gland (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092), and one case each in the oropharynx, submandibular gland, and larynx. At last follow-up (9\u201321\u00a0months; median, 11), four patients developed local recurrence and\/or distant metastases, two died of disease at 11 and 12\u00a0months, one died of other cause, one was alive with disease, and two were disease-free. Three of six tumors harbored\u00a0high risk oncogenic HPV infection (HPV33, HPV18, one unspecified). Histologically, three tumors revealed non-keratinizing transitional cell-like or non-descript morphology with variable mixed inflammatory infiltrate reminiscent of mucoepidermoid or\n                    <jats:italic>DEK<\/jats:italic>\n                    ::\n                    <jats:italic>AFF2<\/jats:italic>\n                    carcinoma (all were HPV-negative), and three were HPV-associated (all sinonasal) with multiphenotypic (1) and non-intestinal adenocarcinoma (2) pattern, respectively. One salivary gland tumor showed poorly cohesive large epithelioid cells with prominent background inflammation and expressed AR and GATA3, in line with a possible salivary duct carcinoma variant. Two tumors were conventional SCC. Targeted RNA sequencing revealed an in-frame\n                    <jats:italic>FGFR3<\/jats:italic>\n                    ::\n                    <jats:italic>TACC3<\/jats:italic>\n                    fusion in all cases. This series highlights heterogeneity of head and neck carcinomas harboring\n                    <jats:italic>FGFR3<\/jats:italic>\n                    ::\n                    <jats:italic>TACC3<\/jats:italic>\n                    fusions, which segregates into three categories: (1) unclassified HPV-negative category, morphologically distinct from SCC and other entities; (2) heterogeneous group of HPV-associated carcinomas; and (3) conventional SCC. A driver role of the\n                    <jats:italic>FGFR3<\/jats:italic>\n                    ::\n                    <jats:italic>TACC3<\/jats:italic>\n                    fusion in the first category (as a potential distinct entity)\u00a0remains to be further studied. In the light of available\n                    <jats:italic>FGFR<\/jats:italic>\n                    -targeting therapies, delineation of these tumors and enhanced recognition is recommended.\n                  <\/jats:p>","DOI":"10.1007\/s00428-024-03940-3","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T05:02:19Z","timestamp":1728536539000},"page":"499-510","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["FGFR3::TACC3 fusions in head and neck carcinomas: a study of nine cases highlighting phenotypic heterogeneity, frequent HPV association, and a morphologically distinct subset in favor of a putative entity"],"prefix":"10.1007","volume":"486","author":[{"given":"Abbas","family":"Agaimy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina R.","family":"Antonescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerben E.","family":"Breimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine K.","family":"Dermawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart A.","family":"Kester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Laco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes A.","family":"Rijken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumeal D.","family":"Whaley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Stoehr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Cramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin A.","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"3940_CR1","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1126\/science.1220834","volume":"337","author":"D Singh","year":"2012","unstructured":"Singh D, Chan JM, Zoppoli P, Niola F, Sullivan R, Castano A, Liu EM, Reichel J, Porrati P, Pellegatta S, Qiu K, Gao Z, Ceccarelli M, Riccardi R, Brat DJ, Guha A, Aldape K, Golfinos JG, Zagzag D, Mikkelsen T, Finocchiaro G, Lasorella A, Rabadan R, Iavarone A (2012) Transforming fusions of FGFR and TACC genes in human glioblastoma. 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CRA and JKD serve as members of the editorial board of\n                      Virchows Archiv\n                      . The authors have no financial or non-financial conflicts of interest to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}