{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:52:39Z","timestamp":1791003159387,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"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":["Cytopathology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Fine\u2010needle aspiration (FNA) is central to evaluation of thyroid nodules, yet risk stratification for follicular neoplasm categorized as Bethesda IV (FN\/SFN) remains challenging due to substantial cytologic overlap and evolving diagnostic criteria. This study assesses whether subclassifying FN\/SFN cases by nuclear atypia, oncocytic features, together with molecular testing, improves risk of malignancy (ROM) estimation and clinical decision\u2010making.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was a retrospective review of thyroid FNAs classified as Bethesda Category IV at our institution from January 2015 to December 2024. FN\/SFN cases were subcategorized as FN\/SFN, FN\/SFN with PTC\u2010like nuclear features (FN\/SFN\u2010PTC) and oncocytic follicular neoplasm (FN\/SFN\u2010O). Risk of malignancy (ROM) was calculated for each subcategory and correlated with surgical resections when available. Molecular testing results, including mutational analysis and molecular risk, were extracted from Afirma and ThyGeNEXT\/ThyraMIR. Chi\u2010squared analysis was used for statistical analysis with\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05 being significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 13,865 thyroid FNAs, 449 (3.2%) were classified as Bethesda Category IV; 146 had surgical follow\u2010up (1.1%). FN\/SFN\u2010PTC demonstrated the highest ROM (50.3%) and neoplastic rate (78.1%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03). RAS\u2010like mutations were the most common molecular alteration (27.4%), but were not significantly predictive of malignancy. BRAF\u2010like alterations were exclusive to FN\/SFN\u2010PTC and all BRAF\u2010like cases were malignant. FN\/SFN\u2010O showed elevated ROM and neoplastic rate compared with conventional FN. FN\/SFN\u2010O had the highest proportion of mutation\u2010negative cases (89.4%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05); however, 40% of mutation\u2010negative FN\/SFN\u2010O cases were malignant on surgical resection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cytologic subcategorization of Bethesda Category IV thyroid FNA specimens provides clinically meaningful and statistically significant risk stratification. PTC\u2010like nuclear atypia is associated with higher ROMs and neoplastic rates. Oncocytic features show distinct molecular characteristics in which mutation\u2010negative status does not reliably exclude malignancy, highlighting a diagnostic challenge. Molecular testing complements cytologic subcategorization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cyt.70119","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:56:33Z","timestamp":1790999793000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytologic Sub\u2010Categorization of Bethesda Category\n                    <scp>IV<\/scp>\n                    Nodules Has Significant Clinicopathologic Outcomes"],"prefix":"10.1111","author":[{"given":"John","family":"Stack","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine New York Presbyterian Hospital\/Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1812-8729","authenticated-orcid":false,"given":"Momin T.","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine New York Presbyterian Hospital\/Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2353-0162","authenticated-orcid":false,"given":"Hansen","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine New York Presbyterian Hospital\/Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1001\/jama.2018.0898","article-title":"The Diagnosis and Management of Thyroid Nodules: A Review","volume":"319","author":"Durante C.","year":"2018","journal-title":"JAMA"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1210\/jc.2018-01674","article-title":"Reducing the Number of Unnecessary Thyroid Biopsies While Improving Diagnostic Accuracy: Toward the \u2018Right\u2019 TIRADS","volume":"104","author":"Grani G.","year":"2019","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2009.0274"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2017.0500"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902\u2010020\u20100530\u20109"},{"key":"e_1_2_12_7_1","first-page":"1039","article-title":"The 2023 Bethesda System for Reporting Thyroid Cytopathology","volume":"33","author":"Ali S. 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