{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:49:07Z","timestamp":1791618547412,"version":"4.3.4"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp;amp; Neck"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Sinonasal carcinomas are aggressive and often locally invasive at presentation, with no universally accepted treatment approach. Histopathologic\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant status appears to be associated with improved treatment response and survival. However, the clinical significance of histopathologic classification among IDH2\u2010mutant sinonasal carcinomas, as well as that of IDH2 mutation status within SNUC, remains unclear and long\u2010term clinical outcome data are limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Records from a prospectively maintained skull\u2010base database at a large, tertiary care hospital system from 1986 to 2024 were reviewed. Patients with a diagnosis of SNUC or sinonasal tumor of any histopathology positive for IDH2 R172 mutation were identified. SMARCB1\u2010deficient, SMARCA4\u2010deficient, NUT sinonasal carcinomas, and other small round cell mimickers were excluded. After histopathologic confirmation, 22\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant SNUC, 14\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant non\u2010SNUC, and 8\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010wildtype SNUC cases were amenable to comprehensive clinicopathologic data review. A presence of\n                      <jats:italic>IDH2<\/jats:italic>\n                      R172 and pathogenic\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations was determined by molecular testing and\/or by immunohistochemistry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median age at diagnosis was 58\u2009years and 61% of patients were male. The majority of patients presented with T4b disease (41% of\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant SNUC; 57% of\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant non\u2010SNUC; 75% of\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010wildtype SNUC;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.3). There was no significant difference in the proportion of patients presenting with orbital invasion (55%\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant SNUC; 64%\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant non\u2010SNUC; 75% of\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010wildtype SNUC;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.7) or intracranial invasion (82%\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant SNUC; 79%\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant non\u2010SNUC; 75% of\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010wildtype SNUC;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.7). On histopathology, there was no significant difference in perineural invasion and margin status between the three subgroups (\n                      <jats:italic>p\u2009&gt;\u20090.6<\/jats:italic>\n                      ). A greater proportion of\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant non\u2010SNUCs had\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations (67%) than\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant SNUC (31%) and\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010wildtype SNUC (29%) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.13). Across the cohort, 41% of patients received neoadjuvant chemotherapy, with a partial response by RECIST criteria in 94% of patients across the subgroups. Median follow\u2010up was 28\u2009months (IQR 11\u201364\u2009months). 5\u2010year DSS of 73% in\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant SNUC, 75% in\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant non\u2010SNUC and 80% in\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010wildtype SNUC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.78). 5\u2010year RFS was 53% in\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant SNUC, 48% in\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010mutant non\u2010SNUC and 43% in\n                      <jats:italic>IDH2<\/jats:italic>\n                      \u2010wildtype SNUC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.78).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Upfront assessment of\n                      <jats:italic>IDH2<\/jats:italic>\n                      mutation status in sinonasal carcinoma patients may be warranted to select patients for clinical trials with IDH\u2010inhibitors. However, no significant differences in the extent of disease at presentation or response to induction chemotherapy were observed according to histopathologic classification among IDH2\u2010mutant sinonasal carcinomas or IDH2 mutation status within SNUC. Larger series are required to determine the prognostic significance of\n                      <jats:italic>IDH2<\/jats:italic>\n                      mutation status in sinonasal carcinoma patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70495","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:07:10Z","timestamp":1791616030000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010Term Outcomes of\n                    <scp>\n                      <i>IDH2<\/i>\n                    <\/scp>\n                    \u2010Mutant Sinonasal Carcinomas Compared With\n                    <scp>\n                      <i>IDH2<\/i>\n                    <\/scp>\n                    \u2010Wild Type Sinonasal Undifferentiated Carcinoma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7784-1244","authenticated-orcid":false,"given":"Daniel W.","family":"Scholfield","sequence":"first","affiliation":[{"name":"Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Lucas","family":"Axiotakis","sequence":"additional","affiliation":[{"name":"Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1698-9610","authenticated-orcid":false,"given":"Robbie","family":"Woods","sequence":"additional","affiliation":[{"name":"Head and Neck Service Beaumont Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Tai","sequence":"additional","affiliation":[{"name":"Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana","family":"Eagan","sequence":"additional","affiliation":[{"name":"Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6279-9987","authenticated-orcid":false,"given":"Lillian A.","family":"Boe","sequence":"additional","affiliation":[{"name":"Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3634-5119","authenticated-orcid":false,"given":"Emma","family":"Finnegan","sequence":"additional","affiliation":[{"name":"Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenric","family":"Tam","sequence":"additional","affiliation":[{"name":"Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-906X","authenticated-orcid":false,"given":"Jennifer","family":"Cracchiolo","sequence":"additional","affiliation":[{"name":"Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-2571","authenticated-orcid":false,"given":"Lara","family":"Dunn","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7636-5426","authenticated-orcid":false,"given":"Ian","family":"Ganly","sequence":"additional","affiliation":[{"name":"Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6104-7967","authenticated-orcid":false,"given":"Marc A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4905-8946","authenticated-orcid":false,"given":"Snjezana","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0000000000000391"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00353"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4915"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2016.239"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0285-x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001420"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2024.100448"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1854-7"},{"issue":"9","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1097\/PAS.0000000000001697","article-title":"IDH2 R172 Mutations Across 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