{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:18:39Z","timestamp":1788866319693,"version":"build-2803163510"},"reference-count":28,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2025,4]]},"abstract":"\n Background:<\/jats:title>\n The international medullary thyroid carcinoma (MTC) grading system (IMTCGS) has been proposed as an independent tool to predict disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS). We aimed to evaluate the performance of IMTCGS in our series of sporadic MTCs and to compare its predictive power with conventional prognostic factors.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n In a retrospective cohort study, we evaluated data from 314 patients with sporadic MTC, all managed at the Pisa University Hospital. We divided patients according to the extent of the disease at diagnosis into localized (183\/314, 58.3%) (confined to the thyroid), regional (100\/314, 31.8%) (limited to the neck, involving surrounding thyroid tissues and\/or regional lymph nodes), and distant (31\/314, 9.9%) (distant metastases) disease. Data about somatic mutations were available in 212\/314 (67.5%) patients. Expert pathologists differentiated high- and low-grade tumors.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n According to the IMTCGS, 115\/314 (36.6%) had high- and 199\/314 (63.4%) patients had low-grade tumors. Patients with high-grade tumors showed higher preoperative calcitonin levels compared with low-grade (542 vs. 76 pg\/mL,\n p<\/jats:italic>\n < 0.01) as well as larger tumor size (2.3 vs. 1.1 cm,\n p<\/jats:italic>\n < 0.01) and more frequent multifocality (22.6 vs. 12.1%,\n p<\/jats:italic>\n = 0.01), minimal extrathyroidal extension (30.4 vs. 9.5%,\n p<\/jats:italic>\n < 0.01), and lymph node metastases (63.5 vs. 27.6%,\n p<\/jats:italic>\n < 0.01). Overall, patients with high-grade showed lower DSS, LRFS, and DMFS (\n p<\/jats:italic>\n < 0.01). Grouping the whole cohort according to different disease extent at diagnosis, only in the case of localized disease, patients with high-grade tumors had significantly lower LRFS compared with low-grade. Similarly, in the other subgroups, we did not identify any difference in DSS, LRFS, and DMFS. Moreover, in the case of\n RET<\/jats:italic>\n aggressive mutations, no differences in DSS, LRFS, and DMFS were observed between high- and low-grade tumors.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n We confirmed the usefulness of IMTCGS in predicting DSS, LRFS, and DMFS. However, it finds the best utility in patients with a lower risk of recurrence and mortality, identifying those rare cases with more aggressive clinical behavior. Conversely, when laterocervical lymph nodes (N1), distant metastasis (M1), or\n RET<\/jats:italic>\n mutations, particularly\n M918T<\/jats:italic>\n or\n indels<\/jats:italic>\n , are already present at diagnosis, the role of IMTCGS in predicting DSS, DMFS, and LRFS becomes less relevant.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/thy.2024.0444","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T03:38:26Z","timestamp":1739245106000},"page":"387-396","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["The Usefulness of the International Grading System in the Management of Sporadic Medullary Thyroid Carcinoma"],"prefix":"10.1177","volume":"35","author":[{"given":"Alessandro","family":"Prete","sequence":"first","affiliation":[{"name":"Endocrine Unit 2, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liborio","family":"Torregrossa","sequence":"additional","affiliation":[{"name":"Pathology Unit 3, Department of Surgical, Medical and Molecular Pathology, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Gambale","sequence":"additional","affiliation":[{"name":"Endocrine Unit 2, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Ciampi","sequence":"additional","affiliation":[{"name":"Endocrine Unit 2, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Ramone","sequence":"additional","affiliation":[{"name":"Endocrine Unit 2, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Romei","sequence":"additional","affiliation":[{"name":"Endocrine Unit 2, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Cappagli","sequence":"additional","affiliation":[{"name":"Endocrine Unit 2, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-9161","authenticated-orcid":false,"given":"Paolo","family":"Piaggi","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, University of Pisa, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Ugolini","sequence":"additional","affiliation":[{"name":"Pathology Unit 3, Department of Surgical, Medical and Molecular Pathology, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Materazzi","sequence":"additional","affiliation":[{"name":"Endocrine Surgery Unit - Department of Surgical, Medical and Molecular Pathology and Critical Area, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5333-9257","authenticated-orcid":false,"given":"Rossella","family":"Elisei","sequence":"additional","affiliation":[{"name":"Endocrine Unit 2, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4263-4717","authenticated-orcid":false,"given":"Antonio","family":"Matrone","sequence":"additional","affiliation":[{"name":"Endocrine Unit 2, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103833"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2019.09.030"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2016.04.053"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22244"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-22542-5_10"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad061"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz400"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0335"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-18-0056"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac325"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01329"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2023.0279"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100235"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2023.152112"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-022-09719-z"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2022.0217"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100244"},{"key":"e_1_3_6_19_2","volume-title":"World Health Organization (WHO) Classification of Tumours of Endocrine Organs","author":"LiVolsi V","year":"2017","unstructured":"LiVolsi V, , Dr A, , Komminoth P, et al. 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