{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:50:25Z","timestamp":1791262225359,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K08 HL151911"],"award-info":[{"award-number":["K08 HL151911"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC) are rare aggressive malignancies with no established prognostic markers. Because features of POU2F3+ small cell lung carcinomas have been identified in both tumors, we evaluated immunostaining for POU2F3, a tuft cell transcription factor, and KIT, a tuft\u2010progenitor marker, to determine whether SNECs\/SNUCs exhibit a tuft cell lineage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively studied patients with rare sinonasal malignancies treated between 2010 and 2025 at the University of Pennsylvania. Archived specimens underwent immunohistochemistry for KIT, POU2F3, SOX9, TRPM5, ASCL1, and IDH2 R172 mutations. Clinical, radiological, and treatment data were collected. Associations with overall survival (OS) and disease\u2010free survival (DFS) were evaluated using Kaplan\u2013Meier and Cox regression analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      KIT was expressed in 90.2% of SNECs (\n                      <jats:italic>N<\/jats:italic>\n                      = 11) and 54.6% of SNUCs (\n                      <jats:italic>N<\/jats:italic>\n                      = 11), with the KIT\n                      <jats:sup>+<\/jats:sup>\n                      POU2F3\n                      <jats:sup>+<\/jats:sup>\n                      phenotype in 72.7% and 18.2%, respectively. KIT\/POU2F3 expression correlated with SOX9 and TRPM5, and KIT\/POU2F3 phenotypes correlated with IDH2 R172 mutation status (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.015). KIT\n                      <jats:sup>+<\/jats:sup>\n                      POU2F3\n                      <jats:sup>+<\/jats:sup>\n                      tumors had significantly improved OS (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.004) and DFS (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001). Univariable analysis showed that lack of double positive KIT\/POU2F3 phenotype predicted decreased OS (HR: 12.24; 95% CI: 2.29\u2013226.78;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001) and DFS (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). In multivariable analyses, this association persisted for OS in models including histologic subtype or IDH2 mutation status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Results indicate that a subgroup of SNECs and SNUCs expresses a tuft cell\u2010associated marker profile. KIT\n                      <jats:sup>+<\/jats:sup>\n                      POU2F3\n                      <jats:sup>+<\/jats:sup>\n                      SNECS and SNUCs have markedly improved OS and DFS suggesting these markers have diagnostic, prognostic and potentially therapeutic utility.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alr.70283","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:51:40Z","timestamp":1791258700000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nasal Tuft Cell Markers Are Predictive of Overall Survival in Sinonasal Neuroendocrine and Sinonasal Undifferentiated Carcinomas"],"prefix":"10.1002","author":[{"given":"Nikolina","family":"Dioufa","sequence":"first","affiliation":[{"name":"Department of Pathology Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4850-0680","authenticated-orcid":false,"given":"Ricardo V.","family":"Bruneto","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3634-2067","authenticated-orcid":false,"given":"Jennifer E.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithin D.","family":"Adappa","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James N.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Monell Chemical Senses Center  Philadelphia Pennsylvania USA"},{"name":"Corporal Michael J. Crescenz VA Medical Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8399-364X","authenticated-orcid":false,"given":"Michael A.","family":"Kohanski","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.23262"},{"issue":"1","key":"e_1_2_10_3_1","first-page":"72","article-title":"The Contemporary Management of Cancers of the Sinonasal Tract in Adults","volume":"73","author":"Thawani R.","year":"2023","journal-title":"CA: A Cancer Journal for Clinicians"},{"key":"e_1_2_10_4_1","volume-title":"Head and Neck Tumours: WHO Classification of Tumours","author":"WHO","year":"2022"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001908"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10006\u2010024\u201001240\u20103"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.path.2024.07.010"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21497"},{"issue":"2","key":"e_1_2_10_9_1","first-page":"94","article-title":"Incidence and Survival Patterns of Sinonasal Undifferentiated Carcinoma in the United States","volume":"76","author":"Chambers K. 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