{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:07:05Z","timestamp":1787314025229,"version":"build-2736575974"},"reference-count":55,"publisher":"Walter de Gruyter GmbH","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Medullary thyroid carcinoma (MTC) is a distinct type of malignant thyroid tumor in cell origin, biological behavior, and natural history. It accounts for 1.6% of all thyroid cancers and presents either sporadically or as a hereditary disease, the latter occurring as a part of multiple endocrine neoplasia (MEN) 2A and MEN2B syndromes or as a familial MTC disease with no other manifestations. The gene responsible for the hereditary form is the rearranged during transfection (RET) gene, a proto-oncogene located to human chromosome 10. Most pediatric MTC cases have been discovered after genetic testing investigations, leading to the concept of prophylactic surgery in presymptomatic patients. Therefore, the genetic status of the child, along with serum calcitonin levels and ultrasonographic findings, determine the appropriate age for prophylactic surgical intervention. Nevertheless, a diagnosis at an early stage of MTC warrants total thyroidectomy and central lymph node dissection with the addition of lateral\/contralateral lymph node dissection depending on the tumor size, ultrasonographic evidence of neck disease, or calcitonin levels. Conversely, locally advanced\/unresectable or metastatic MTC is primarily treated with multikinase inhibitors, while more specific RET inhibitors are being tested in clinical trials with promising results.<\/jats:p>","DOI":"10.1515\/jpem-2021-0502","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T18:10:25Z","timestamp":1633025425000},"page":"1-10","source":"Crossref","is-referenced-by-count":4,"title":["Medullary thyroid carcinoma in children: current state of the art and future perspectives"],"prefix":"10.1515","volume":"35","author":[{"given":"Andreas","family":"Kiriakopoulos","sequence":"first","affiliation":[{"name":"Fifth Department of Surgery , \u201cEvgenidion Hospital\u201d, National and Kapodistrian University of Athens School of Medicine , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5021-5152","authenticated-orcid":false,"given":"Anastasia","family":"Dimopoulou","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery , University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens School of Medicine , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos","family":"Nastos","sequence":"additional","affiliation":[{"name":"Third Department of Surgery , University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens School of Medicine , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Dimopoulou","sequence":"additional","affiliation":[{"name":"Second Department of Pediatrics , \u201cP & A Kyriakou\u201d Children\u2019s Hospital, National and Kapodistrian University of Athens School of Medicine , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Dimopoulou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology , General Hospital \u201cHippokration\u201d , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Menenakos","sequence":"additional","affiliation":[{"name":"Fifth Department of Surgery , \u201cEvgenidion Hospital\u201d, National and Kapodistrian University of Athens School of Medicine , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Zavras","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery , University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens School of Medicine , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"2023040100325819893_j_jpem-2021-0502_ref_001","doi-asserted-by":"crossref","unstructured":"Graves, CE, Gosnell, JE. Medullary thyroid carcinoma in children. Semin Pediatr Surg 2011;29:150921. https:\/\/doi.org\/10.1016\/j.sempedsurg.2020.150921.","DOI":"10.1016\/j.sempedsurg.2020.150921"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_002","doi-asserted-by":"crossref","unstructured":"Hogan, AR, Zhuge, Y, Perez, EA, Koniaris, LG, Lew, JI, Sola, JE. Pediatric thyroid carcinoma: incidence and outcomes in 1753 patients. J Surg Res 2009;156:167\u201372. https:\/\/doi.org\/10.1016\/j.jss.2009.03.098.","DOI":"10.1016\/j.jss.2009.03.098"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_003","doi-asserted-by":"crossref","unstructured":"Paulson, VA, Rudzinski, ER, Hawkins, DS. Thyroid Cancer in the Pediatric Population. Genes (Basel) 2019;10:723https:\/\/doi.org\/10.3390\/genes10090723.","DOI":"10.3390\/genes10090723"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_004","doi-asserted-by":"crossref","unstructured":"Wells, SA, Asa, SL, Dralle, H, Elisei, R, Evans, DB, Gagel, RF, et al.. Revised American thyroid association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015;25:567\u2013610. https:\/\/doi.org\/10.1089\/thy.2014.0335.","DOI":"10.1089\/thy.2014.0335"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_005","doi-asserted-by":"crossref","unstructured":"Takahashi, M, Ritz, J, Cooper, GM. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell 1985;42:581\u20138. https:\/\/doi.org\/10.1016\/0092-8674(85)90115-1.","DOI":"10.1016\/0092-8674(85)90115-1"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_006","doi-asserted-by":"crossref","unstructured":"Bai, Y, Niu, D, Yao, Q, Lin, D, Kakudo, K. Updates in the advances of sporadic medullary thyroid carcinoma: from the molecules to the clinic. Gland Surg 2020;9:1847\u201356. https:\/\/doi.org\/10.21037\/gs-2019-catp-21.","DOI":"10.21037\/gs-2019-catp-21"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_007","doi-asserted-by":"crossref","unstructured":"Hedayati, M, Zarif Yeganeh, M, Sheikholeslami, S, Afsari, F. Diversity of mutations in the RET proto-oncogene and its oncogenic mechanism in medullary thyroid cancer. Crit Rev Clin Lab Sci 2016;53:217\u201327. https:\/\/doi.org\/10.3109\/10408363.2015.1129529.","DOI":"10.3109\/10408363.2015.1129529"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_008","doi-asserted-by":"crossref","unstructured":"Accardo, G, Conzo, G, Esposito, D, Gambardella, C, Mazzella, M, Castaldo, F, et al.. Genetics of medullary thyroid cancer: an overview. 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J Pediatr Surg 2018;53:283\u20135. https:\/\/doi.org\/10.1016\/j.jpedsurg.2017.11.015.","DOI":"10.1016\/j.jpedsurg.2017.11.015"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_023","doi-asserted-by":"crossref","unstructured":"Garc\u00e9s Visier, C, Espinoza Vega, M, Guill\u00e9n Redondo, P, Ollero Fresno, JC, Souto Romero, H, Luis Huertas, A, et al.. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A in children: a single centre experience. J Pediatr Endocrinol Metab 2019;32:889\u201393. https:\/\/doi.org\/10.1515\/jpem-2019-0121.","DOI":"10.1515\/jpem-2019-0121"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_024","doi-asserted-by":"crossref","unstructured":"Shepet, K, Alhefdhi, A, Lai, N, Mazeh, H, Sippel, R, Chen, H. Hereditary medullary thyroid cancer: age-appropriate thyroidectomy improves disease-free survival. Ann Surg Oncol 2013;20:1451\u20135. https:\/\/doi.org\/10.1245\/s10434-012-2757-9.","DOI":"10.1245\/s10434-012-2757-9"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_025","doi-asserted-by":"crossref","unstructured":"Al-Kurd, A, Gross, DJ, Zangen, D, Atlan, K, Mazeh, H, Grozinsky-Glasberg, S. Bilateral medullary thyroid carcinoma in a 3-year-old female patient with multiple endocrine neoplasia 2A syndrome undergoing prophylactic thyroidectomy: should current guidelines be revised? Eur Thyroid J 2018;7:267\u201371. https:\/\/doi.org\/10.1159\/000489170.","DOI":"10.1159\/000489170"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_026","doi-asserted-by":"crossref","unstructured":"Kluijfhout, WP, van Beek, DJ, Verrijn Stuart, AA, Lodewijk, L, Valk, GD, van der Zee, DC, et al.. Postoperative complications after prophylactic thyroidectomy for very young patients with multiple endocrine neoplasia type 2: retrospective cohort analysis. Medicine 2015;94:e1108. https:\/\/doi.org\/10.1097\/md.0000000000001108.","DOI":"10.1097\/MD.0000000000001108"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_027","doi-asserted-by":"crossref","unstructured":"Raval, MV, Sturgeon, C, Bentrem, DJ, Elaraj, DM, Stewart, AK, Winchester, DJ, et al.. Influence of lymph node metastases on survival in pediatric medullary thyroid cancer. J Pediatr Surg 2010;45:1947\u201354. https:\/\/doi.org\/10.1016\/j.jpedsurg.2010.06.013.","DOI":"10.1016\/j.jpedsurg.2010.06.013"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_028","doi-asserted-by":"crossref","unstructured":"Fox, E, Widemann, BC, Chuk, MK, Marcus, L, Aikin, A, Whitcomb, PO, et al.. Vandetanib in children and adolescents with multiple endocrine neoplasia type 2b associated medullary thyroid carcinoma. Clin Canc Res 2013;19:4239\u201348. https:\/\/doi.org\/10.1158\/1078-0432.ccr-13-0071.","DOI":"10.1158\/1078-0432.CCR-13-0071"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_029","doi-asserted-by":"crossref","unstructured":"Kraft, IL, Akshintala, S, Derse-Anthony, C, Steinberg, SM, Venzon, DJ, Dombi, E, et al.. Outcomes of children with hereditary medullary thyroid carcinoma (MTC) treated with vandetanib. J Clin Oncol 2017;35:10540. https:\/\/doi.org\/10.1200\/jco.2017.35.15_suppl.10540.","DOI":"10.1200\/JCO.2017.35.15_suppl.10540"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_030","doi-asserted-by":"crossref","unstructured":"Lodish, M, Gkourogianni, A, Bornstein, E, Sinaii, N, Fox, E, Chuk, M, et al.. Patterns of thyroid hormone levels in pediatric medullary thyroid carcinoma patients on vandetanib therapy. Int J Pediatr Endocrinol 2015;2015:3. https:\/\/doi.org\/10.1186\/1687-9856-2015-3.","DOI":"10.1186\/1687-9856-2015-3"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_031","doi-asserted-by":"crossref","unstructured":"Aller, S, Popescu, A, Rao, S, Morgan, E, Gosiengfiao, Y. Transient partial response to sorafenib treatment in an adolescent patient with MEN2B syndrome and end-stage medullary thyroid carcinoma. Pediatr Blood Canc 2012;58:98\u2013100. https:\/\/doi.org\/10.1002\/pbc.23032.","DOI":"10.1002\/pbc.23032"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_032","doi-asserted-by":"crossref","unstructured":"Ortiz, MV, Gerdemann, U, Raju, SG, Henry, D, Smith, S, Rothenberg, SM, et al.. Activity of the highly specific RET inhibitor selpercatinib (LOXO-292) in pediatric patients with tumors harboring RET gene alterations. JCO Precis Oncol 2020;14:PO.19.00401. https:\/\/doi.org\/10.1200\/PO.19.00401.","DOI":"10.1200\/PO.19.00401"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_033","doi-asserted-by":"crossref","unstructured":"Raue, F, Frank-Raue, K. Update on multiple endocrine neoplasia type 2: focus on medullary thyroid carcinoma. J Environ Sci 2018;2:933\u201343. https:\/\/doi.org\/10.1210\/js.2018-00178.","DOI":"10.1210\/js.2018-00178"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_034","doi-asserted-by":"crossref","unstructured":"Santoro, M, Carlomagno, F, Romano, A, Bottaro, DP, Dathan, NA, Grieco, M, et al.. Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science 1995;20:381\u20133. https:\/\/doi.org\/10.1126\/science.7824936.","DOI":"10.1126\/science.7824936"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_035","doi-asserted-by":"crossref","unstructured":"Larouche, V, Akirov, A, Thomas, CM, Krzyzanowska, MK, Ezzat, S. A primer on the genetics of medullary thyroid cancer. Curr Oncol 2019;26:389\u201394. https:\/\/doi.org\/10.3747\/co.26.5553.","DOI":"10.3747\/co.26.5553"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_036","doi-asserted-by":"crossref","unstructured":"Elisei, R, Bottici, V, Cappagli, V, Ramone, T, Tacito, A, Ciampi, R, et al.. Clinical utility of genetic diagnosis for sporadic and hereditary medullary thyroid carcinoma. Ann Endocrinol 2019;80:187\u201390. https:\/\/doi.org\/10.1016\/j.ando.2019.04.014.","DOI":"10.1016\/j.ando.2019.04.014"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_037","doi-asserted-by":"crossref","unstructured":"Niccoli-Sire, P, Murat, A, Rohmer, V, Franc, S, Chabrier, G, Baldet, L, et al.. Familial medullary thyroid carcinoma with noncysteine RET mutations: phenotype-genotype relationship in a large series of patients. J Clin Endocrinol Metab 2001;86:3746\u201353. https:\/\/doi.org\/10.1210\/jcem.86.8.7767.","DOI":"10.1210\/jcem.86.8.7767"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_038","doi-asserted-by":"crossref","unstructured":"Dvorakova, S, Vaclavikova, E, Sykorova, V, Vcelak, J, Novak, Z, Duskova, J, et al.. Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinomas. Mol Cell Endocrinol 2008;284:21\u20137. https:\/\/doi.org\/10.1016\/j.mce.2007.12.016.","DOI":"10.1016\/j.mce.2007.12.016"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_039","doi-asserted-by":"crossref","unstructured":"Cote, GJ, Grubbs, EG, Hofmann, MC. Thyroid C-cell biology and oncogenic transformation. Recent Results Canc Res 2015;204:1\u201339. https:\/\/doi.org\/10.1007\/978-3-319-22542-5_1.","DOI":"10.1007\/978-3-319-22542-5_1"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_040","doi-asserted-by":"crossref","unstructured":"Viola, D, Romei, C, Elisei, R. Medullary thyroid carcinoma in children. Endocr Dev 2014;26:202\u201313. https:\/\/doi.org\/10.1159\/000363165.","DOI":"10.1159\/000363165"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_041","doi-asserted-by":"crossref","unstructured":"Chen, H, Sippel, RS, O\u2019Dorisio, MS, Vinik, AI, Lloyd, RV, Pacak, K, North American Neuroendocrine Tumor Society (NANETS). The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas 2010;39:775\u201383. https:\/\/doi.org\/10.1097\/mpa.0b013e3181ebb4f0.","DOI":"10.1097\/MPA.0b013e3181ebb4f0"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_042","doi-asserted-by":"crossref","unstructured":"Kahaly, GJ, Algeciras-Schimnich, A, Davis, TE, Diana, T, Feldkamp, J, Karger, S, et al.. United States and European multicenter prospective study for the analytical performance and clinical validation of a novel sensitive fully automated immunoassay for calcitonin. Clin Chem 2017;63:1489\u201396. https:\/\/doi.org\/10.1373\/clinchem.2016.270009.","DOI":"10.1373\/clinchem.2016.270009"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_043","doi-asserted-by":"crossref","unstructured":"Wang, TS, Ocal, IT, Sosa, JA, Cox, H, Roman, S. Medullary thyroid carcinoma without marked elevation of calcitonin: a diagnostic and surveillance dilemma. Thyroid 2008;18:889\u201394. https:\/\/doi.org\/10.1089\/thy.2007.0413.","DOI":"10.1089\/thy.2007.0413"},{"key":"2023040100325819893_j_jpem-2021-0502_ref_044","doi-asserted-by":"crossref","unstructured":"Kushchayev, SV, Kushchayeva, YS, Tella, SH, Glushko, T, Pacak, K, Teytelboym, OM. Medullary thyroid carcinoma: an update on imaging. 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