{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:32:00Z","timestamp":1772994720182,"version":"3.50.1"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Medullary thyroid carcinoma (MTC) with high proliferative potential or tumor necrosis is classified as high\u2010grade MTC. Progression from low\u2010 to high\u2010grade MTC has rarely been documented. We report a case in which a sporadic MTC transitioned from low\u2010 to high\u2010grade after the initial therapy. A 62\u2010year\u2010old man with low\u2010grade MTC underwent total thyroidectomy and bilateral neck dissection. Recurrence was identified postoperatively, and the surgical specimen of the lymph node revealed metastatic MTC with high\u2010grade features. Treatment was initiated with vandetanib followed by selpercatinib, with no significant efficacy. Debulking surgery was performed for five recurrent lesions. Surgical specimens of the tumor after chemotherapy showed increased aggression, characterized by high Ki\u201067 index and decreased calcitonin expression. The patient eventually died due to brain metastasis. This case highlights the potential for MTC to progress from low\u2010 to high\u2010grade and underscores the importance of ongoing evaluations for recurrent disease.<\/jats:p>","DOI":"10.1111\/pin.70089","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T17:12:26Z","timestamp":1770052346000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Medullary Thyroid Carcinoma That Progressed From Low\u2010 to High\u2010Grade During Treatment: A Case Report"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-7645","authenticated-orcid":false,"given":"Masaomi","family":"Sen","sequence":"first","affiliation":[{"name":"Department of Endocrine Surgery Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takenori","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Integrated Diagnostic Pathology Nippon Medical School  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukako","family":"Shintani\u2010Domoto","sequence":"additional","affiliation":[{"name":"Department of Integrated Diagnostic Pathology Nippon Medical School  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Kazusaka","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mami","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuta","family":"Nagaoka","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoo","family":"Jikuzono","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuko","family":"Sakanushi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5560-0706","authenticated-orcid":false,"given":"Iwao","family":"Sugitani","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuji","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Department of Integrated Diagnostic Pathology Nippon Medical School  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0532-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001505"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01329"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-022-09707-3"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-19-1-152"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000168114.90852.a6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2023.152112"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100235"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(1984)54:4<657::AID-CNCR2820540412>3.0.CO;2-V"},{"issue":"6","key":"e_1_2_9_11_1","first-page":"964","article-title":"Prognostic Significance of Calcitonin Immunoreactivity, Amyloid Staining, and Flow Cytometric DNA Measurements in Medullary Thyroid Carcinoma","volume":"110","author":"Pyke C. M.","year":"1991","journal-title":"Surgery"},{"key":"e_1_2_9_12_1","first-page":"1193","article-title":"Tumor Grade Predicts for Calcitonin Doubling Times and Disease\u2010Specific Outcomes After Resection of Medullary Thyroid Carcinoma","volume":"32","author":"Nigam A.","year":"2022","journal-title":"Thyroid"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309719"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-024-09817-0"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.23.00053"}],"container-title":["Pathology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pin.70089","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pin.70089","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pin.70089","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:21:10Z","timestamp":1772983270000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pin.70089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":14,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/pin.70089"],"URL":"https:\/\/doi.org\/10.1111\/pin.70089","archive":["Portico"],"relation":{},"ISSN":["1320-5463","1440-1827"],"issn-type":[{"value":"1320-5463","type":"print"},{"value":"1440-1827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-09-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70089"}}