{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:05:53Z","timestamp":1790193953725,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Thymic carcinoids are rare neuroendocrine tumors arising in the anterior mediastinum, often diagnosed at an advanced stage due to nonspecific clinical manifestations. Their management remains challenging because of the paucity of data, rarity of occurrence, and aggressive biological behavior compared to other well-differentiated neuroendocrine neoplasms. Methods: We conducted a comprehensive review of the current literature focusing on the classification, clinical presentation, diagnostics, treatment options, prognostic factors, and emerging experimental therapies for thymic carcinoids. Emphasis was placed on integrating recent molecular and therapeutic advances into clinical practice. Results: Surgical resection remains the cornerstone of treatment for localized disease, while systemic therapies such as everolimus, somatostatin analogs, platinum-based chemotherapy, and peptide receptor radionuclide therapy (PRRT) are options for advanced cases. Novel diagnostic modalities, including NETest, 64Cu-DOTATATE PET, and 18F-FDOPA PET, offer promise in early detection and disease monitoring. Molecular insights, particularly involving MEN1, ATRX, and DAXX mutations, pave the way for individualized targeted therapies. Immunotherapy and radioimmunotherapy represent emerging, albeit still experimental, approaches. Prognosis largely depends on tumor stage, differentiation, resectability, and functional activity, with a high recurrence rate necessitating prolonged surveillance. Conclusions: Thymic carcinoids pose significant diagnostic and therapeutic challenges. Advances in molecular profiling, novel imaging techniques, and systemic therapies offer hope for improved outcomes. Given the disease rarity, continued collaboration through registries and multicenter studies is essential to refine evidence-based management strategies.<\/jats:p>","DOI":"10.3390\/cancers17121975","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T06:19:28Z","timestamp":1749795568000},"page":"1975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Recent Clinical and Molecular Advances in the Management of Thymic Carcinoids: A Comprehensive Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3635-1772","authenticated-orcid":false,"given":"Aleksandra","family":"Pi\u00f3rek","sequence":"first","affiliation":[{"name":"Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"P\u0142u\u017ca\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-3229","authenticated-orcid":false,"given":"Dariusz M.","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3324-0900","authenticated-orcid":false,"given":"Maciej","family":"Krzakowski","sequence":"additional","affiliation":[{"name":"Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1097\/SLA.0b013e3181dd4ec4","article-title":"Thymic neuroendocrine tumors: A SEER database analysis of 160 patients","volume":"251","author":"Gaur","year":"2010","journal-title":"Ann. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1159\/000472255","article-title":"Thymic Neuroendocrine Neoplasms: Biological Behaviour and Therapy","volume":"105","author":"Jia","year":"2017","journal-title":"Neuroendocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1097\/JTO.0000000000000630","article-title":"The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification","volume":"10","author":"Travis","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Barone, P.D., and Zhang, C. (2024). Neuroendocrine neoplasms of the thymus. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1465775"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.annonc.2021.01.003","article-title":"Lung and thymic carcinoids: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up\u2606","volume":"32","author":"Baudin","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S1448","DOI":"10.21037\/jtd.2017.02.02","article-title":"Neuroendocrine tumors of the thymus and mediastinum","volume":"9","author":"Bohnenberger","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s12020-022-03099-4","article-title":"Thymic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1","volume":"77","author":"Yliaska","year":"2022","journal-title":"Endocrine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.hoc.2015.09.003","article-title":"Bronchial and Thymic Carcinoid Tumors","volume":"30","author":"Litvak","year":"2016","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s11154-021-09660-2","article-title":"Ectopic Cushing\u2019s syndrome due to thymic neuroendocrine tumours: A systematic review","volume":"22","author":"Peiro","year":"2021","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/00000658-199807000-00015","article-title":"Thymic carcinoids in multiple endocrine neoplasia type 1","volume":"228","author":"Teh","year":"1998","journal-title":"Ann. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1210\/jc.2004-1155","article-title":"Thymic neuroendocrine carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: The Italian series","volume":"90","author":"Ferolla","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1210\/jc.2002-021314","article-title":"Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1","volume":"88","author":"Gibril","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/00005792-199701000-00002","article-title":"Clinicopathologic studies of thymic carcinoids in multiple endocrine neoplasia type 1","volume":"76","author":"Teh","year":"1997","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1210\/jc.2012-1230","article-title":"Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1)","volume":"97","author":"Thakker","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.canlet.2004.10.027","article-title":"Chromosomal imbalances in sporadic neuroendocrine tumours of the thymus","volume":"223","author":"Rieker","year":"2005","journal-title":"Cancer Lett."},{"key":"ref_16","first-page":"351","article-title":"[Prevalence of the neuroendocrine phenotype in thymus neoplasms]","volume":"54","author":"Ferolla","year":"2002","journal-title":"Chir. Ital."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.thorsurg.2014.05.007","article-title":"Thymic neuroendocrine tumors","volume":"24","author":"Lausi","year":"2014","journal-title":"Thorac. Surg. Clin."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhai, Y., Zeng, Q., Bi, N., Zhou, Z., Xiao, Z., Hui, Z., Chen, D., Wang, L., Wang, J., and Liu, W. (2022). A Single Center Analysis of Thymic Neuroendocrine Tumors. Cancers, 14.","DOI":"10.3390\/cancers14194944"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jtcvs.2014.08.061","article-title":"Outcome of primary neuroendocrine tumors of the thymus: A joint analysis of the International Thymic Malignancy Interest Group and the European Society of Thoracic Surgeons databases","volume":"149","author":"Filosso","year":"2015","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.ejcts.2009.10.026","article-title":"Primary neuroendocrine tumours of the thymus: A clinicopathologic and prognostic study in 19 patients","volume":"37","author":"Cardillo","year":"2010","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/gutjnl-2011-300831","article-title":"Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)","volume":"61","author":"Ramage","year":"2012","journal-title":"Gut"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s40792-018-0459-7","article-title":"Cushing\u2019s syndrome caused by ACTH-producing thymic typical carcinoid with local invasion and regional lymph node metastasis: A case report","volume":"4","author":"Fujiwara","year":"2018","journal-title":"Surg. Case Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1530\/EJE-19-0877","article-title":"MANAGEMENT OF ENDOCRINE DISEASE: Cushing\u2019s syndrome due to ectopic ACTH secretion: An expert operational opinion","volume":"182","author":"Young","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4381","DOI":"10.1002\/cncr.26029","article-title":"Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion: The University of Texas MD Anderson Cancer Center Experience","volume":"117","author":"Ejaz","year":"2011","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1210\/jc.2004-2527","article-title":"Cushing\u2019s syndrome due to ectopic corticotropin secretion: Twenty years\u2019 experience at the National Institutes of Health","volume":"90","author":"Ilias","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1530\/eje.1.02278","article-title":"Ectopic ACTH syndrome: Our experience with 25 cases","volume":"155","author":"Salgado","year":"2006","journal-title":"Eur. J. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1530\/EJE-15-0968","article-title":"Prevalence and clinical features of the ectopic ACTH syndrome in patients with gastroenteropancreatic and thoracic neuroendocrine tumors","volume":"174","author":"Kamp","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20150341","DOI":"10.1259\/bjr.20150341","article-title":"CT and MRI findings of thymic carcinoid","volume":"90","author":"Shimamoto","year":"2017","journal-title":"Br. J. Radiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"66","DOI":"10.2967\/jnumed.117.202275","article-title":"Appropriate Use Criteria for Somatostatin Receptor PET Imaging in Neuroendocrine Tumors","volume":"59","author":"Hope","year":"2018","journal-title":"J. Nucl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11864-019-0677-7","article-title":"Peptide Receptor Radiotherapy: Current Approaches and Future Directions","volume":"20","author":"Kong","year":"2019","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.jtcvs.2003.09.058","article-title":"Multidisciplinary treatment of advanced thymic neuroendocrine carcinoma (carcinoid): Report of a successful case and review of the literature","volume":"127","author":"Filosso","year":"2004","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cllc.2020.11.010","article-title":"Mutation Profile of Thymic Carcinoma and Thymic Neuroendocrine Tumor by Targeted Next-generation Sequencing","volume":"22","author":"Sakane","year":"2021","journal-title":"Clin. Lung Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1002\/gcc.22183","article-title":"Tumor genetics and survival of thymic neuroendocrine neoplasms: A multi-institutional clinicopathologic study","volume":"53","author":"Strobel","year":"2014","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Granberg, D., Juhlin, C.C., Falhammar, H., and Hedayati, E. (2023). Lung Carcinoids: A Comprehensive Review for Clinicians. Cancers, 15.","DOI":"10.3390\/cancers15225440"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1530\/EJE-16-0546","article-title":"Whole exome sequencing of thymic neuroendocrine tumor with ectopic ACTH syndrome","volume":"176","author":"Li","year":"2017","journal-title":"Eur. J. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s12022-021-09668-z","article-title":"Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?","volume":"32","author":"Volante","year":"2021","journal-title":"Endocr. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liu, M., Hu, W., Zhang, Y., Zhang, N., Chen, L., Lin, Y., Wang, Y., Luo, Y., Guo, Y., and Chen, M. (2022). Clinical implications of immune checkpoint markers and immune infiltrates in patients with thymic neuroendocrine neoplasms. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.917743"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/S0140-6736(15)00817-X","article-title":"Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): A randomised, placebo-controlled, phase 3 study","volume":"387","author":"Yao","year":"2016","journal-title":"Lancet"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1111\/1759-7714.14887","article-title":"Everolimus in combination with octreotide LAR in thymic atypical carcinoid","volume":"14","author":"Sakane","year":"2023","journal-title":"Thorac. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1093\/annonc\/mdv252","article-title":"Pazopanib in pretreated advanced neuroendocrine tumors: A phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE)","volume":"26","author":"Grande","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1158\/1078-0432.CCR-19-3014","article-title":"Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Neuroendocrine Tumors: Results From the Phase II KEYNOTE-158 Study","volume":"26","author":"Strosberg","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Garcia-Torralba, E., Garcia-Lorenzo, E., Doger, B., Spada, F., and Lamarca, A. (2024). Immunotherapy in Neuroendocrine Neoplasms: A Diamond to Cut. Cancers, 16.","DOI":"10.3390\/cancers16142530"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/12\/1975\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:51:22Z","timestamp":1760032282000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/12\/1975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,13]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cancers17121975"],"URL":"https:\/\/doi.org\/10.3390\/cancers17121975","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,13]]}}}