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These tumors show significant morphological and immunophenotypic diversity. We present five novel head and neck carcinomas harboring\n                    <jats:italic>AFF2<\/jats:italic>\n                    rearrangements involving previously unreported fusion partners. Five cases (3 males, 2 females; ages 35\u201372\u00a0years) presented with tumors in the sinonasal region (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094) and parotid gland (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091), measuring between 3.3 and 6.3\u00a0cm. RNA sequencing identified fusions involving\n                    <jats:italic>AFF2<\/jats:italic>\n                    with\n                    <jats:italic>H3-3A<\/jats:italic>\n                    ,\n                    <jats:italic>EWSR1<\/jats:italic>\n                    ,\n                    <jats:italic>CHD4<\/jats:italic>\n                    (two cases: neck lymph node metastasis, which turned out to be sinonasal primary and parotid mass), and\n                    <jats:italic>NUCKS1<\/jats:italic>\n                    . Tumors harboring\n                    <jats:italic>H3-3A<\/jats:italic>\n                    ::\n                    <jats:italic>AFF2<\/jats:italic>\n                    and\n                    <jats:italic>NUCKS1<\/jats:italic>\n                    ::\n                    <jats:italic>AFF2<\/jats:italic>\n                    fusions exhibited bland transitional cell-like morphology with acantholytic changes similar to classic\n                    <jats:italic>DEK<\/jats:italic>\n                    ::\n                    <jats:italic>AFF2<\/jats:italic>\n                    carcinoma; the\n                    <jats:italic>NUCKS1<\/jats:italic>\n                    fusion also demonstrated clear cell features. In contrast, the\n                    <jats:italic>EWSR1<\/jats:italic>\n                    ::\n                    <jats:italic>AFF2<\/jats:italic>\n                    fusion tumor showed high-grade adenocarcinoma morphology with focal neuroendocrine marker expression, lacking p63 and CK5\/6. The two\n                    <jats:italic>CHD4<\/jats:italic>\n                    ::\n                    <jats:italic>AFF2<\/jats:italic>\n                    fusion cases demonstrated neuroendocrine differentiation; one was a cytokeratin-negative small blue round cell carcinoma, and the other showed mixed squamoid-neuroendocrine features with strong cytokeratin and p63 expression. All tumors demonstrated consistent AFF2 immunoreactivity. These findings suggest that\n                    <jats:italic>AFF2<\/jats:italic>\n                    -rearranged tumors form a spectrum of carcinomas with diverse morphologies, immunophenotypes, and differentiation patterns. Given the consistent involvement of the\n                    <jats:italic>AFF2<\/jats:italic>\n                    gene and uniform AFF2 immunohistochemical positivity despite morphological heterogeneity, we propose naming this entity AFF2 carcinoma.\n                  <\/jats:p>","DOI":"10.1007\/s00428-025-04140-3","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T16:39:28Z","timestamp":1749573568000},"page":"345-354","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expanding the spectrum of AFF2 carcinoma: clinical, morphological, immunohistochemical, and molecular characteristics of five cases harboring alternate fusions"],"prefix":"10.1007","volume":"488","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0365-3667","authenticated-orcid":false,"given":"Gerben E.","family":"Breimer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin D.","family":"Hyrcza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0685-7614","authenticated-orcid":false,"given":"Elan","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2189-7342","authenticated-orcid":false,"given":"Sophie C.","family":"Prendergast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4141-5280","authenticated-orcid":false,"given":"Anne","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Todorovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9640-2482","authenticated-orcid":false,"given":"Doreen","family":"Palsgrove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Heinhuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4579-3249","authenticated-orcid":false,"given":"Johannes A.","family":"Rijken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8259-9971","authenticated-orcid":false,"given":"Lennart A.","family":"Kester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuihong","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9552-3549","authenticated-orcid":false,"given":"Ilan","family":"Weinreb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9743-4360","authenticated-orcid":false,"given":"Justin A.","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"4140_CR1","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1111\/pin.12727","volume":"68","author":"CA French","year":"2018","unstructured":"French CA (2018) NUT Carcinoma: Clinicopathologic features, pathogenesis, and treatment. 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