{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:31:46Z","timestamp":1790796706957,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytopathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n Thyroid nodules classified as atypia of undetermined significance (AUS) within the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) present a diagnostic challenge, with a risk of malignancy (ROM) of 5% to 50%. In 2017, TBSRTC introduced AUS subcategories to enhance ROM assessment. This study explores the correlation between AUS subclassification, molecular mutations, and surgical outcomes.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Retrospective analysis was performed of 114 AUS cases with molecular profiling by ThyroSeqV3 and surgical follow\u2010up. AUS subcategories as defined by TBSRTC included: AUS\u2010Architectural, AUS\u2010Nuclear, AUS\u2010Nuclear and Architectural, and AUS\u2010H\u00fcrthle cell. Pathology diagnoses were categorised as benign, malignant, or borderline, including noninvasive follicular thyroid neoplasm with papillary\u2010like nuclear features (NIFTP).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of the 114 nodules, 32.5% were AUS\u2010Architectural, 28.9% AUS\u2010Nuclear and Architectural, 18.4% AUS\u2010Nuclear, 19.3% AUS\u2010H\u00fcrthle cell, and 0.9% AUS\u2010Not Otherwise Specified. Papillary carcinoma, predominantly follicular variant, was the most common diagnosis (47.4%), followed by benign lesions (34.2%) and NIFTP (9.6%). RAS family mutations were the most prevalent molecular alteration (34.2%) followed by\n DICER1<\/jats:italic>\n ,\n EIF1AX<\/jats:italic>\n ,\n EXH1<\/jats:italic>\n mutations, CNA and GEP (29.8%).\n THADA<\/jats:italic>\n fusions,\n PTEN<\/jats:italic>\n ,\n TSHR<\/jats:italic>\n and\n BRAFK601E<\/jats:italic>\n mutations were identified in 10.5% of cases, while high\u2010risk mutations such as\n BRAF V600E<\/jats:italic>\n ,\n TERT<\/jats:italic>\n , and\n TP53<\/jats:italic>\n were found in 8.8% of cases. AUS subcategories demonstrated distinct molecular profiles and were linked to varying surgical outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n AUS subcategorization is associated with specific molecular profiles and surgical outcomes, supporting the subclassification of AUS cases per TBSRTC guidelines for improved risk stratification and clinical management. Further prospective studies with larger cohorts are necessary for validation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cyt.13503","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T23:48:49Z","timestamp":1745538529000},"page":"66-75","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Malignancy Risk, Molecular Mutations, and Surgical Outcomes of Thyroid Nodules Classified as Atypia of Undetermined Significance in the Bethesda System: A Comprehensive Analysis"],"prefix":"10.1111","volume":"37","author":[{"given":"Caroline","family":"Bourque","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Sciences McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1728-860X","authenticated-orcid":false,"given":"Gianluca","family":"Savoia","sequence":"additional","affiliation":[{"name":"Faculty of Science McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxine","family":"Noik","sequence":"additional","affiliation":[{"name":"Faculty of Science McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Florianova","sequence":"additional","affiliation":[{"name":"Department of Pathology McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saruchi","family":"Bandargal","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina Daniela","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Jewish General Hospital Montreal Quebec Canada"},{"name":"Department of Otolaryngology\u2013Head and Neck Surgery McGill University Health Center Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Payne","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Jewish General Hospital Montreal Quebec Canada"},{"name":"Department of Otolaryngology\u2013Head and Neck Surgery McGill University Health Center Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6490-4189","authenticated-orcid":false,"given":"Marc Philippe","family":"Pusztaszeri","sequence":"additional","affiliation":[{"name":"Department of Pathology McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0020"},{"key":"e_1_2_12_3_1","volume-title":"The Bethesda System for Reporting Thyroid Cytopathology. 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Y.Osamura G.Kl\u00f6ppel andJ.Rosai \u201cWHO Classification of Tumours of Endocrine Organs WHO\/IARC Classification of Tumours \u201d2017.4th Edition Vol 10."},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000451020"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath\u20102019\u2010205985"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21823"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jasc.2023.10.001"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2024.01.002"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14246097"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol31100441"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae355"},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","DOI":"10.1177\/19160216251336687","article-title":"Role of Publicly\u2010Funded Molecular Testing in Surgical Management of Thyroid Nodules Within Canadian Medicare: Clinical Assessment of ThyroSeqv3 Molecular Test Pilot Project at McGill University","author":"Bandargal S.","year":"2025","journal-title":"Journal of Otolaryngology\u2014Head & Neck Surgery"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2014.10.004"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.22809"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12092563"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae354"}],"container-title":["Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cyt.13503","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T13:51:16Z","timestamp":1765288276000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.13503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,24]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/cyt.13503"],"URL":"https:\/\/doi.org\/10.1111\/cyt.13503","archive":["Portico"],"relation":{},"ISSN":["0956-5507","1365-2303"],"issn-type":[{"value":"0956-5507","type":"print"},{"value":"1365-2303","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,24]]},"assertion":[{"value":"2025-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}