{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T04:22:13Z","timestamp":1771302133840,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T00:00:00Z","timestamp":1602460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytopathology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The cytological diagnosis of follicular\u2010patterned thyroid lesions is challenging, especially since the World Health Organisation classification has recognised non\u2010invasive follicular thyroid neoplasm with papillary\u2010like features. These entities are often classified as indeterminate on cytology. Molecular testing has been proposed to help classify indeterminate nodules. <jats:italic>RAS<\/jats:italic> and K601E <jats:italic>BRAF<\/jats:italic> mutations are mostly encountered in follicular\u2010patterned lesions, but their diagnostic value is not well established. Nuclear scores have also been proposed to help classify indeterminate lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the correlation between cytological features and histology and to assess nuclear scores in a series of indeterminate <jats:italic>RAS<\/jats:italic> or <jats:italic>BRAF<\/jats:italic> K601E positive thyroid nodules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The cytological parameters of 69 indeterminate <jats:italic>RAS<\/jats:italic> or <jats:italic>BRAF<\/jats:italic> K601E\u2010positive thyroid nodules were evaluated. The Strickland and Maletta scores and a new nuclear score were assessed. Diagnosis of malignant, benign or indolent neoplasms was confirmed in each case by histology. Malignant and indolent nodules were considered <jats:italic>surgical nodules<\/jats:italic>, and adenomas <jats:italic>non\u2010surgical nodule<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Surgical nodules were associated with the presence of ground glass nuclei (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.001), grooves (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) or irregular nuclear membranes (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.01) on cytology. Nuclear scores were more often \u22652 in surgical nodules compared to benign ones (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), with high sensitivity, but a low negative predictive value.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Analysis of nuclear features is useful to distinguish non\u2010surgical from surgical nodules in indeterminate FNAs. Although nuclear scores are not ideal rule\u2010out tests for indeterminate <jats:italic>RAS<\/jats:italic> or <jats:italic>BRAF<\/jats:italic> K601E positive nodules, they seem useful to screen non\u2010molecular tested or non\u2010mutated indeterminate FNAs. This work shows that meticulous analysis of nuclear features on cytological specimens can be useful to distinguish non\u2010surgical nodules (adenoma) from surgical nodules in indeterminate FNAs. Although nuclear scores are not rule\u2010out tests for indeterminate RAS or <jats:italic>BRAF<\/jats:italic> K601E positive nodules, they are useful in screening non\u2010molecular tested or non\u2010mutated indeterminate FNAs for surgery.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cyt.12904","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T12:01:36Z","timestamp":1598616096000},"page":"37-44","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cytological features and nuclear scores: Diagnostic tools in preoperative fine needle aspiration of indeterminate thyroid nodules with <i>RAS<\/i> or <i>BRAF<\/i> K601E mutations?"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7651-0889","authenticated-orcid":false,"given":"Lucie","family":"Ravella","sequence":"first","affiliation":[{"name":"Centre de Biologie et Pathologie Sud Centre Hospitalier Lyon Sud Pierre B\u00e9nite France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Lopez","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department Centre Hospitalier Lyon Sud Pierre B\u00e9nite France"},{"name":"Team EMT and Cancer Cell Plasticity Cancer Research Center of Lyon Lyon 1 University Villeurbanne France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7oise","family":"Descotes","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department Centre Hospitalier Lyon Sud Pierre B\u00e9nite France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joris","family":"Giai","sequence":"additional","affiliation":[{"name":"CNRS UMR 5558 Laboratoire de Biom\u00e9trie et Biologie Evolutive Equipe Biostatistique\u2010Sant\u00e9 Villeurbanne France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Lapras","sequence":"additional","affiliation":[{"name":"Radiology Department Centre Hospitalier Lyon Sud Pierre B\u00e9nite France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie\u2010Laure","family":"Denier","sequence":"additional","affiliation":[{"name":"Radiology Department Centre Hospitalier Lyon Sud Pierre B\u00e9nite France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7oise","family":"Borson\u2010Chazot","sequence":"additional","affiliation":[{"name":"Endocrinology Department Groupement Hospitalier Est Bron France"},{"name":"Facult\u00e9 de M\u00e9decine Lyon Est Universite Claude Bernard Lyon 1 Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Christophe","family":"Lifante","sequence":"additional","affiliation":[{"name":"Endocrine Surgery Department Centre Hospitalier Lyon Sud France"},{"name":"Facult\u00e9 de M\u00e9decine Lyon Sud Universite Oullins France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myriam","family":"Decaussin\u2010Petrucci","sequence":"additional","affiliation":[{"name":"Centre de Biologie et Pathologie Sud Centre Hospitalier Lyon Sud Pierre B\u00e9nite France"},{"name":"INSERM1052 CNRS5286 Cancer Research Center of Lyon Lyon 1 University Villeurbanne France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0020"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2009.0110"},{"key":"e_1_2_9_4_1","unstructured":"WHO Classification of Tumours of Endocrine Organs. Vol.10.IARC WHO Classification of Tumours. Lloyd RV.2017."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqw126"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-17-0513"},{"key":"e_1_2_9_7_1","unstructured":"AliSZ CibasES.The Bethesda system for reporting thyroid cytopathology: definitions criteria and explanatory notes.2018. Accessed January 23 2019."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21922"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2016.03.014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.0386"},{"issue":"5","key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.5858\/2010-0664-RAIR.1","article-title":"Molecular diagnostics of thyroid tumors","volume":"135","author":"Nikiforov YE","year":"2011","journal-title":"Arch Pathol Lab Med"},{"issue":"11","key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"4413","DOI":"10.1210\/jc.2016-1775","article-title":"Papillary thyroid carcinoma with rare exon 15 BRAF mutation has indolent behavior: a single\u2010institution experience","volume":"101","author":"Torregrossa L","year":"2016","journal-title":"J Clin Endocrinol Metabolism"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0227"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cyt.12493"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0628"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP171940.DSCR"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0612"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21631"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2016.04.054"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3396"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.21292"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21848"},{"issue":"12","key":"e_1_2_9_23_1","first-page":"1671","article-title":"Thyroid carcinoma, version 2.2014 featured updates to the NCCN guidelines","volume":"12","author":"Tuttle RM","year":"2014","journal-title":"JNCCN"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-020-05487-1"}],"container-title":["Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cyt.12904","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cyt.12904","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cyt.12904","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T11:11:53Z","timestamp":1693739513000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.12904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,12]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1111\/cyt.12904"],"URL":"https:\/\/doi.org\/10.1111\/cyt.12904","archive":["Portico"],"relation":{},"ISSN":["0956-5507","1365-2303"],"issn-type":[{"value":"0956-5507","type":"print"},{"value":"1365-2303","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,12]]},"assertion":[{"value":"2020-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}