{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:22:31Z","timestamp":1781940151307,"version":"3.54.5"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013003","name":"University of Cagliari","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to compare clinicopathological features of familial non-medullary thyroid cancer (FNMTC) and sporadic non-medullary thyroid cancer (sNMTC) and assess whether age at onset contributes to the different behavior of these 2 entities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A retrospective study including 31 patients with FNMTC, and 31 age- and sex-matched patients with sNMTC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Histological variant, multifocality, tumor infiltration, angioinvasion, TNM stage, lymph node metastasis, BRAF and p53 expression, ATA risk stratification, and the presence of chronic lymphocytic thyroiditis (CLT) were compared between groups. Then, we identified a cutoff age to stratify patients by age of onset (\u226435 vs &amp;gt;35 years).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>FNMTC presented at a more advanced stage at diagnosis compared to sNMTC, with a higher proportion of medium-high TNM stages. Among FNMTC, early-onset (\u226435 years) cases showed higher BRAF expression, more frequent lymph node metastases, a higher proportion of medium-high TNM stages, and intermediate-to-high ATA risk compared to late-onset cases (&amp;gt;35 years). Medium-high TNM stage, BRAF expression, and lymph node metastases were observed more frequently in early onset FNMTC than in age-matched sNMTC. Late-onset FNMTC patients exhibited a higher prevalence of CLT than early-onset FNMTC and late-onset sNMTC patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings underscore the relevance of age at disease onset in shaping the clinical phenotypes of FNMTC. The distinct pathological features of early-onset vs late-onset FNMTC suggest different pathophysiological mechanisms, with the former likely driven by direct genetic\/oncogenic alterations, and the latter influenced by autoimmune thyroiditis\u2013related carcinogenesis, a hypothesis that warrants further investigation in larger prospective studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag059","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T11:25:56Z","timestamp":1776079556000},"page":"510-518","source":"Crossref","is-referenced-by-count":1,"title":["Early familial non-medullary thyroid cancer: differences with late-onset and sporadic forms"],"prefix":"10.1093","volume":"194","author":[{"given":"Chiara","family":"Mura","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari , Cagliari 09042 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Corrias","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari , Cagliari 09042 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Lecca","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari , Cagliari 09042 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Letizia","family":"Lai","sequence":"additional","affiliation":[{"name":"Pathology Unit, San Giovanni di Dio Hospital , Cagliari 09124 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Luigi","family":"Canu","sequence":"additional","affiliation":[{"name":"Surgery Unit, Department of Surgical Sciences, University of Cagliari, Cagliari 09042 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Medas","sequence":"additional","affiliation":[{"name":"Surgery Unit, Department of Surgical Sciences, University of Cagliari, Cagliari 09042 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Mariotti","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari , Cagliari 09042 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro Giorgio","family":"Cal\u00f2","sequence":"additional","affiliation":[{"name":"Surgery Unit, Department of Surgical Sciences, University of Cagliari, Cagliari 09042 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Caria","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Biochemistry, Biology and Genetics Unit, University of Cagliari, Cagliari 09042 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-4040","authenticated-orcid":false,"given":"Giulia","family":"Lanzolla","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari , Cagliari 09042 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Boi","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari , Cagliari 09042 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"issue":"4","key":"2026041712363043700_lvag059-B1","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/S2213-8587(22)00035-3","article-title":"The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020","volume":"10","author":"Pizzato","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"11","key":"2026041712363043700_lvag059-B2","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1007\/S002680010233","article-title":"Familial papillary thyroid carcinoma: genetics, criteria for diagnosis, clinical features, and surgical treatment","volume":"24","author":"Musholt","year":"2000","journal-title":"World J Surg"},{"issue":"2","key":"2026041712363043700_lvag059-B3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1089\/THY.2006.16.181","article-title":"On the prevalence of familial nonmedullary thyroid cancer in multiply affected kindreds","volume":"16","author":"Charkes","year":"2006","journal-title":"Thyroid"},{"issue":"2","key":"2026041712363043700_lvag059-B4","doi-asserted-by":"publisher","first-page":"e855","DOI":"10.1210\/clinem\/dgaa798","article-title":"Role of age at diagnosis in defining potential familial nonmedullary thyroid cancer in kindreds with two affected members","volume":"106","author":"Capezzone","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2026041712363043700_lvag059-B5","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1677\/ERC-08-0080","article-title":"Familial non-medullary thyroid carcinoma displays the features of clinical anticipation suggestive of a distinct biological entity","volume":"15","author":"Capezzone","year":"2008","journal-title":"Endocr Relat Cancer"},{"issue":"4","key":"2026041712363043700_lvag059-B6","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1089\/THY.2011.0163","article-title":"The long-term outcomes of the second generation of familial nonmedullary thyroid carcinoma are more aggressive than sporadic cases","volume":"22","author":"Park","year":"2012","journal-title":"Thyroid"},{"issue":"9","key":"2026041712363043700_lvag059-B7","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1089\/THY.2013.0079","article-title":"Familial nonmedullary thyroid carcinoma","volume":"23","author":"Mazeh","year":"2013","journal-title":"Thyroid"},{"issue":"4","key":"2026041712363043700_lvag059-B8","doi-asserted-by":"publisher","first-page":"395","DOI":"10.4103\/0366-6999.225054","article-title":"Familial nonmedullary thyroid carcinoma: a retrospective analysis of 117 families","volume":"131","author":"Zhang","year":"2018","journal-title":"Chin Med J (Engl)"},{"issue":"1","key":"2026041712363043700_lvag059-B9","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1089\/THY.2011.0192","article-title":"In patients with thyroid cancer of follicular cell origin, a family history of nonmedullary thyroid cancer in one first-degree relative is associated with more aggressive disease","volume":"22","author":"Mazeh","year":"2012","journal-title":"Thyroid"},{"issue":"8","key":"2026041712363043700_lvag059-B10","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1007\/S00268-002-6615-Y","article-title":"Familial nonmedullary thyroid carcinoma characterized by multifocality and a high recurrence rate in a large study population","volume":"26","author":"Uchino","year":"2002","journal-title":"World J Surg"},{"key":"2026041712363043700_lvag059-B11","doi-asserted-by":"publisher","first-page":"948786","DOI":"10.1155\/2011\/948786","article-title":"Familial papillary thyroid carcinoma: a retrospective analysis","volume":"2011","author":"McDonald","year":"2011","journal-title":"J Oncol"},{"issue":"12","key":"2026041712363043700_lvag059-B12","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1097\/01.MLG.0000149454.91005.65","article-title":"Familial non-medullary thyroid cancer: a matched-case control study","volume":"114","author":"Maxwell","year":"2004","journal-title":"Laryngoscope"},{"issue":"2","key":"2026041712363043700_lvag059-B13","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1530\/EJE-13-0865","article-title":"Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical\/prognostic behaviour","volume":"170","author":"Pinto","year":"2014","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"2026041712363043700_lvag059-B14","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1089\/THY.2009.0406","article-title":"Clinical characteristics and outcome of familial nonmedullary thyroid cancer: a retrospective controlled study","volume":"21","author":"Robenshtok","year":"2011","journal-title":"Thyroid"},{"issue":"2","key":"2026041712363043700_lvag059-B15","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1002\/JSO.23447","article-title":"Familial history of non-medullary thyroid cancer is an independent prognostic factor for tumor recurrence in younger patients with conventional papillary thyroid carcinoma","volume":"109","author":"Lee","year":"2014","journal-title":"J Surg Oncol"},{"issue":"1","key":"2026041712363043700_lvag059-B16","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/J.SURG.2008.08.004","article-title":"Biological behavior and prognosis of familial papillary thyroid carcinoma","volume":"145","author":"Ito","year":"2009","journal-title":"Surgery"},{"issue":"1","key":"2026041712363043700_lvag059-B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/THY.2015.0020","article-title":"2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer","volume":"26","author":"Haugen","year":"2016","journal-title":"Thyroid"},{"issue":"4","key":"2026041712363043700_lvag059-B18","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1159\/000468928","article-title":"Thyroid autoimmunity and thyroid cancer: review focused on cytological studies","volume":"6","author":"Boi","year":"2017","journal-title":"Eur Thyroid J"},{"issue":"9","key":"2026041712363043700_lvag059-B19","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1089\/thy.2024.0142","article-title":"The association between lymphocytic thyroiditis and papillary thyroid cancer harboring mutant BRAF: a systematic review and meta-analysis","volume":"34","author":"Perampalam","year":"2024","journal-title":"Thyroid"},{"issue":"2","key":"2026041712363043700_lvag059-B20","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3322\/caac.21388","article-title":"The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more \u201cpersonalized\u201d approach to cancer staging","volume":"67","author":"Amin","year":"2017","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"2026041712363043700_lvag059-B21","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/S41467-022-28120-2","article-title":"Lymphocyte infiltration and thyrocyte destruction are driven by stromal and immune cell components in Hashimoto's thyroiditis","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat Commun"},{"issue":"6","key":"2026041712363043700_lvag059-B22","doi-asserted-by":"publisher","first-page":"R253","DOI":"10.1530\/EJE-14-0960","article-title":"Endocrine tumours: familial nonmedullary thyroid carcinoma is a more aggressive disease: a systematic review and meta-analysis","volume":"172","author":"Wang","year":"2015","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"2026041712363043700_lvag059-B23","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1007\/S40618-020-01435-X","article-title":"Familial non-medullary thyroid cancer: a critical review","volume":"44","author":"Capezzone","year":"2021","journal-title":"J Endocrinol Invest"},{"issue":"1","key":"2026041712363043700_lvag059-B24","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/JSO.22064","article-title":"Allelic loss of susceptibility loci and the occurrence of BRAF and RAS mutations in patients with familial non-medullary thyroid cancer","volume":"105","author":"Na","year":"2012","journal-title":"J Surg Oncol"},{"key":"2026041712363043700_lvag059-B25","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.3892\/OL.2015.3386","article-title":"RAS\/BRAF mutational status in familial non-medullary thyroid carcinomas: a retrospective study","volume":"10","author":"Landriscina","year":"2015","journal-title":"Oncol Lett"},{"key":"2026041712363043700_lvag059-B26","doi-asserted-by":"publisher","first-page":"616974","DOI":"10.3389\/FONC.2021.616974","article-title":"Comparison between clinicopathological characteristics, BRAF V600E and TERT promoter mutation of familial non-medullary thyroid carcinomas, and sporadic case","volume":"11","author":"Yang","year":"2021","journal-title":"Front Oncol"},{"key":"2026041712363043700_lvag059-B27","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1089\/THY.2010.0256","article-title":"Prevalence, clinicopathologic features, and somatic genetic mutation profile in familial versus sporadic nonmedullary thyroid cancer","volume":"21","author":"Moses","year":"2011","journal-title":"Thyroid"},{"key":"2026041712363043700_lvag059-B28","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/S40618-017-0757-0","article-title":"High prevalence of papillary thyroid carcinoma in nodular Hashimoto's thyroiditis at the first diagnosis and during the follow-up","volume":"41","author":"Boi","year":"2018","journal-title":"J Endocrinol Invest"},{"issue":"5","key":"2026041712363043700_lvag059-B29","doi-asserted-by":"publisher","first-page":"313","DOI":"10.3275\/8579","article-title":"Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules","volume":"36","author":"Boi","year":"2013","journal-title":"J Endocrinol Invest."},{"key":"2026041712363043700_lvag059-B30","doi-asserted-by":"publisher","first-page":"801925","DOI":"10.3389\/FENDO.2022.801925","article-title":"Hashimoto's thyroiditis: a \u201cDouble-Edged Sword\u201d in thyroid carcinoma","volume":"13","author":"Xu","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026041712363043700_lvag059-B31","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1159\/000486367","article-title":"Effects of chronic lymphocytic thyroiditis on the clinicopathological features of papillary thyroid cancer","volume":"7","author":"Babli","year":"2018","journal-title":"Eur Thyroid J"},{"issue":"10","key":"2026041712363043700_lvag059-B32","doi-asserted-by":"publisher","first-page":"bqab144","DOI":"10.1210\/endocr\/bqab144","article-title":"Pre-existing thyroiditis ameliorates papillary thyroid cancer: insights from a new mouse model","volume":"162","author":"Pani","year":"2021","journal-title":"Endocrinology"},{"key":"2026041712363043700_lvag059-B33","doi-asserted-by":"publisher","first-page":"E1327","DOI":"10.1210\/JC.2011-2096","article-title":"Telomere abnormalities and chromosome fragility in patients affected by familial papillary thyroid cancer","volume":"97","author":"Cantara","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2026041712363043700_lvag059-B34","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1111\/CEN.15004","article-title":"The causal relationship between autoimmune thyroid disorders and telomere length: a Mendelian Randomization and Colocalization Study","volume":"100","author":"Liu","year":"2024","journal-title":"Clin Endocrinol (Oxf)"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejendo\/advance-article-pdf\/doi\/10.1093\/ejendo\/lvag059\/68089876\/lvag059.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/194\/4\/510\/68089876\/lvag059.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/194\/4\/510\/68089876\/lvag059.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T16:36:36Z","timestamp":1776443796000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/194\/4\/510\/8654983"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,6]]}},"URL":"https:\/\/doi.org\/10.1093\/ejendo\/lvag059","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,4]]}}}