{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T23:41:15Z","timestamp":1776382875031,"version":"3.51.2"},"reference-count":27,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,30]],"date-time":"2024-06-30T00:00:00Z","timestamp":1719705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Lynch syndrome (LS) is a genetic disease with increased risk of colorectal cancer and other malignancies. There are few reported cases of thyroid cancer in LS patients. The aim of this study is to investigate the presence of thyroid nodules in LS patients and to explore their association with the genetic features of the disease. Methods: A retrospective and descriptive analysis was conducted to include all LS patients followed at the CEMAD (Centro Malattie Apparato Digerente) of Fondazione Policlinico Universitario A. Gemelli IRCCS. The characteristics of LS disease, gene mutations, and previous history of thyroid disease were evaluated. Majority of patients underwent thyroid ultrasound (US), and nodule cytology was performed when needed. Results: Of a total of 139 patients with LS, 110 patients were included in the study. A total of 103 patients (74%) underwent thyroid ultrasound examinations, and 7 patients (5%) had a previous history of thyroid disease (cancer or multinodular goiter). The mean age was 51.9 years. Thyroid nodules were found in 62 patients (60%) who underwent US, and 9 of them (14%) had suspicious features of malignancy, inducing a fine-needle aspiration biopsy. A cytologic analysis classified 7 of 9 cases (78%) as TIR2 and 2 (22%) as TIR3a. Between patients with nodular thyroid disease (single nodule, multinodular goiter, and cancer), most of them (25 patients, 36% of total) were carriers of the MSH6 mutation, while 22 (32%), 17 (24%), and 5 (7%) had MSH2, MLH1, and PMS2 mutations, respectively. Conclusions: A high prevalence of thyroid nodules was found in patients with LS, especially in MSH6-carrying patients. Performing at least one thyroid ultrasound examination is suggested for the detection of nodular thyroid disease in LS patients. Systematic investigations are needed to estimate their prevalence, features, and risk of malignant transformation.<\/jats:p>","DOI":"10.3390\/genes15070859","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T06:04:18Z","timestamp":1719986658000},"page":"859","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lynch Syndrome and Thyroid Nodules: A Single Center Experience"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9399-4846","authenticated-orcid":false,"given":"Irene","family":"Spinelli","sequence":"first","affiliation":[{"name":"Centro Malattie Apparato Digerente (CEMAD), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Moffa","sequence":"additional","affiliation":[{"name":"Centro per le Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Fianchi","sequence":"additional","affiliation":[{"name":"Centro Malattie Apparato Digerente (CEMAD), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Mezza","sequence":"additional","affiliation":[{"name":"Centro per le Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5170-7055","authenticated-orcid":false,"given":"Francesca","family":"Cinti","sequence":"additional","affiliation":[{"name":"Centro per le Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4506-5193","authenticated-orcid":false,"given":"Gianfranco","family":"Di Giuseppe","sequence":"additional","affiliation":[{"name":"Centro per le Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clelia","family":"Marmo","sequence":"additional","affiliation":[{"name":"Endoscopia Digestiva Chirurgica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Ianiro","sequence":"additional","affiliation":[{"name":"Centro Malattie Apparato Digerente (CEMAD), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-6238","authenticated-orcid":false,"given":"Francesca Romana","family":"Ponziani","sequence":"additional","affiliation":[{"name":"Centro Malattie Apparato Digerente (CEMAD), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Tortora","sequence":"additional","affiliation":[{"name":"Gastroenterologia B, Azienda Ospedaliera Universitaria Integrata Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Elena","family":"Riccioni","sequence":"additional","affiliation":[{"name":"Endoscopia Digestiva Chirurgica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Giaccari","sequence":"additional","affiliation":[{"name":"Centro per le Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6230-1779","authenticated-orcid":false,"given":"Antonio","family":"Gasbarrini","sequence":"additional","affiliation":[{"name":"Centro Malattie Apparato Digerente (CEMAD), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e80","DOI":"10.1136\/flgastro-2022-102123","article-title":"Diagnosis and management of Lynch syndrome","volume":"13","author":"Edwards","year":"2022","journal-title":"Frontline Gastroenterol."},{"key":"ref_2","unstructured":"(2024, March 21). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae) Genetic\/Familial High-Risk Assessment: Colorectal Version 2.2023\u201430 October 2023. Available online: https:\/\/www.nccn.org\/profile?ReturnURL=https%3a%2f%2fwww.nccn.org%2fprofessionals%2fphysician_gls%2fpdf%2fgenetics_colon.pdf."},{"key":"ref_3","unstructured":"(2024, March 21). InSiGHT: Colon Cancer Gene Variant Database. Available online: https:\/\/www.insight-group.org\/syndromes\/lynch-syndrome\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/ajg.2014.435","article-title":"American College of Gastroenterology. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes","volume":"110","author":"Syngal","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s12020-022-03048-1","article-title":"Papillary thyroid carcinoma as first and isolated neoplastic disease in a Lynch syndrome family member with a germline MLH1 mutation","volume":"77","author":"Verrienti","year":"2022","journal-title":"Endocrine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1897-4287-6-1-15","article-title":"Thyroid cancer in a patient with a germline MSH2 mutation. Case report and review of the Lynch syndrome expanding tumour spectrum","volume":"6","author":"Stulp","year":"2008","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/modpathol.3800150","article-title":"Unusual tumors associated with the hereditary nonpolyposis colorectal cancer syndrome","volume":"17","author":"Broaddus","year":"2004","journal-title":"Mod. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.biopha.2015.06.008","article-title":"Papillary thyroid carcinoma (PTC) in Lynch syndrome: Report of two cases and discussion on Lynch syndrome behaviour and genetics","volume":"74","author":"Pelizzo","year":"2015","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","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"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s40618-018-0884-2","article-title":"Italian consensus on diagnosis and treatment of differentiated thyroid cancer: Joint statements of six Italian societies","volume":"41","author":"Pacini","year":"2018","journal-title":"J. Endocrinol. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10689-012-9534-6","article-title":"Cancer spectrum in DNA mismatch repair gene mutation carriers: Results from a hospital based Lynch syndrome registry","volume":"11","author":"Pande","year":"2012","journal-title":"Fam. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s12029-016-9878-5","article-title":"Molecular Profiling of Synchronous Colon Cancers and Anaplastic Thyroid Cancer in a Patient with Lynch Syndrome","volume":"49","author":"Johnson","year":"2018","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1136\/jclinpath-2018-205337","article-title":"Breast tumour resembling tall cell variant of papillary thyroid carcinoma: Case presentation (in a patient with Lynch syndrome)","volume":"71","author":"Gai","year":"2018","journal-title":"J. Clin. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1089\/thy.2010.1641","article-title":"Familial syndromes associated with thyroid cancer in the era of personalized medicine","volume":"20","author":"Richards","year":"2010","journal-title":"Thyroid"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.14309\/ajg.0000000000001747","article-title":"Thyroid Nodules in Children With Familial Adenomatous Polyposis","volume":"117","author":"Smith","year":"2022","journal-title":"Am. J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Aswath, K., Welch, J., Gubbi, S., Veeraraghavan, P., Avadhanula, S., Gara, S.K., Dikoglu, E., Merino, M., Raffeld, M., and Xi, L. (2021). Co-Occurrence of Familial Non-Medullary Thyroid Cancer (FNMTC) and Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Associated Tumors-A Cohort Study. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.653401"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s00268-017-4299-6","article-title":"DNA Mismatch Repair Deficiency Promotes Genomic Instability in a Subset of Papillary Thyroid Cancers","volume":"42","author":"Javid","year":"2018","journal-title":"World J. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.beem.2008.09.017","article-title":"Molecular pathology of thyroid cancer: Diagnostic and clinical implications","volume":"22","author":"Fagin","year":"2008","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.mce.2017.12.004","article-title":"Imbalance in DNA repair machinery is associated with BRAFV600E mutation and tumor aggressiveness in papillary thyroid carcinoma","volume":"472","author":"Lutz","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1007\/s12020-021-02705-1","article-title":"Rare germline variants in DNA repair-related genes are accountable for papillary thyroid cancer susceptibility","volume":"73","author":"Mio","year":"2021","journal-title":"Endocrine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"C281","DOI":"10.4103\/0973-1482.200764","article-title":"MutL homolog 1 expression in thyroid carcinoma and its clinical significance","volume":"12","author":"Lu","year":"2016","journal-title":"J. Cancer Res. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1038\/s41598-021-83177-1","article-title":"Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer","volume":"11","author":"Fujita","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1158\/0008-5472.CAN-09-3290","article-title":"Somatic hypermethylation of MSH2 is a frequent event in Lynch Syndrome colorectal cancers","volume":"70","author":"Nagasaka","year":"2010","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2353\/jmoldx.2008.080031","article-title":"Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry","volume":"10","author":"Shia","year":"2008","journal-title":"J. Mol. Diagn."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"915","DOI":"10.2147\/TCRM.S121812","article-title":"Thyroid cancer in a patient with Lynch syndrome\u2014Case report and literature review","volume":"13","author":"Parker","year":"2017","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"298","DOI":"10.5455\/msm.2021.33.298-303","article-title":"Risk Factors of Synchronous Breast and Thyroid Cancer: A Controlled Multicenter Study and Review of the Literature","volume":"33","author":"Zervoudis","year":"2021","journal-title":"Mater. Socio-Medica"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1002\/lary.27259","article-title":"Multiple simultaneous head and neck cancers in Lynch syndrome: Case report and literature review","volume":"128","author":"Feng","year":"2018","journal-title":"Laryngoscope"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/7\/859\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:08:04Z","timestamp":1760108884000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/7\/859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,30]]},"references-count":27,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["genes15070859"],"URL":"https:\/\/doi.org\/10.3390\/genes15070859","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,30]]}}}