{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:45:08Z","timestamp":1790181908145,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T00:00:00Z","timestamp":1519257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003852","name":"Regione Campania","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The Bethesda System for Reporting Thyroid Cytopathology category of atypia of undetermined significance\/follicular lesion of undetermined significance (AUS\/FLUS) includes fine\u2010needle aspiration (FNA) specimens that cannot straightforwardly be classified as benign or malignant. To determine whether morphological subcategorization based on atypia qualifiers and molecular testing could improve malignancy risk stratification of AUS\/FLUS patients, this study assessed the correlation between these qualifiers and the molecular alterations commonly harbored by thyroid neoplasms.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>A total of 162 AUS\/FLUS cases were subcategorized by atypia qualifiers (H\u00fcrthle cell changes, architectural atypia, and cytologic atypia [CyA]) and were tested for <jats:italic>BRAF<\/jats:italic>, <jats:italic>N\u2010H\u2010KRAS<\/jats:italic>, <jats:italic>RET<\/jats:italic>\/<jats:italic>PTC<\/jats:italic>, and paired box 8 (<jats:italic>PAX8<\/jats:italic>)\/peroxisome proliferator activated receptor \u03b3 (<jats:italic>PPARg<\/jats:italic>) mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>CyA was observed more frequently in mutation\u2010positive AUS\/FLUS (14 of 37 [37.84%]) than mutation\u2010negative AUS\/FLUS (20 of 125 [16.00%]; <jats:italic>P<\/jats:italic> &lt; .0084), and it specifically harbored the <jats:italic>BRAF<\/jats:italic>V600E point mutation. Malignancy was confirmed in the available follow\u2010up. Conversely, although <jats:italic>RAS<\/jats:italic> was the most frequent mutation identified in AUS\/FLUS FNA specimens (26 of 37 cases [70.27%]; <jats:italic>P<\/jats:italic> &lt; .0001), it was distributed across various AUS\/FLUS subcategories and was not significantly associated with a specific atypia qualifier or malignant outcome according to the available follow\u2010up. Rearrangements of both <jats:italic>RET<\/jats:italic>\/<jats:italic>PTC<\/jats:italic> (n = 1) and <jats:italic>PAX8<\/jats:italic>\/<jats:italic>PPARg<\/jats:italic> (n = 3) were rarely retrieved in the FNA samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p><jats:italic>BRAF<\/jats:italic> and <jats:italic>RAS<\/jats:italic> mutations are associated with different AUS\/FLUS qualifiers and hence have different risks of malignancy. Consequently, a hybrid molecular and morphological subcategorization system could improve the malignancy risk stratification of thyroid FNA samples diagnosed as AUS\/FLUS. <jats:bold><jats:italic>Cancer Cytopathol<\/jats:italic> 2018;126:317\u201025.<\/jats:bold> \u00a9 <jats:italic>2018 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.21984","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T00:51:52Z","timestamp":1519347112000},"page":"317-325","source":"Crossref","is-referenced-by-count":40,"title":["Different qualifiers of AUS\/FLUS thyroid FNA have distinct <i>BRAF<\/i>, <i>RAS<\/i>, <i>RET<\/i>\/<i>PTC<\/i>, and <i>PAX8<\/i>\/<i>PPARg<\/i> alterations"],"prefix":"10.1002","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7479-6457","authenticated-orcid":false,"given":"Claudio","family":"Bellevicine","sequence":"first","affiliation":[{"name":"Department of Public Health Federico II University of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Sgariglia","sequence":"additional","affiliation":[{"name":"Department of Public Health Federico II University of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Migliatico","sequence":"additional","affiliation":[{"name":"Department of Public Health Federico II University of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vigliar","sequence":"additional","affiliation":[{"name":"Department of Public Health Federico II University of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"D'Anna","sequence":"additional","affiliation":[{"name":"Department of Public Health Federico II University of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonia","family":"Nacchio","sequence":"additional","affiliation":[{"name":"Department of Public Health Federico II University of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Serra","sequence":"additional","affiliation":[{"name":"Department of Public Health Federico II University of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Malapelle","sequence":"additional","affiliation":[{"name":"Department of Public Health Federico II University of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9846-6682","authenticated-orcid":false,"given":"Massimo","family":"Bongiovanni","sequence":"additional","affiliation":[{"name":"Institute of Pathology Lausanne University Hospital Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1630-5805","authenticated-orcid":false,"given":"Giancarlo","family":"Troncone","sequence":"additional","affiliation":[{"name":"Department of Public Health Federico II University of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPPHLWMI3JV4LA"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000339959"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000366498"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21605"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-60570-8"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21412"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPO0BQ2YSKPXXP"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21411"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21396"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cyt.12243"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cyt.12431"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1469"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0419-z"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0348"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0227"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0583"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2013.0278"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.0386"}],"container-title":["Cancer 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