{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:42:46Z","timestamp":1793911366056,"version":"4.8.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chromophobe thyroid carcinoma (CTC) is a rare thyroid carcinoma with distinct morphology, often occurring in patients with tuberous sclerosis complex (TSC). The molecular drivers remain poorly understood. We report two additional CTC cases and review the literature including genetic query. Patient 1, an 11-year-old boy, had a 10.3-cm bilateral thyroid mass with tumoral capsular and vascular invasion. Microscopically, the tumor showed trabecular and nested growth, prominent cell membranes, raisinoid nuclei, eosinophilic granular cytoplasm, and perinuclear halos resembling chromophobe renal cell carcinoma. The tumor expressed thyroid markers (TTF-1, PAX-8, thyroglobulin) and renal cell markers (colloidal iron, parvalbumin, CD117) with peripheral mitochondrial accentuation by anti-mitochondrial staining. A somatic\n                    <jats:italic>TSC2<\/jats:italic>\n                    p.Y1650Cfs*4 frameshift mutation was identified. Patient 2, a 24-year-old woman, had a 3.8-cm infiltrative, angioinvasive right lobe tumor with similar morphology and marker expression and positive lymph nodes. Molecular analysis showed somatic\n                    <jats:italic>TSC2<\/jats:italic>\n                    c.2071dupC p.R691Pfs*12 and\n                    <jats:italic>TSC2<\/jats:italic>\n                    c.2353C\u2009&gt;\u2009T p.Q785* mutations. A cBioPortal query (2285 cases) found\n                    <jats:italic>TSC1<\/jats:italic>\n                    alterations in 2% and\n                    <jats:italic>TSC2<\/jats:italic>\n                    in 1%, mostly deletions, enriched in poorly differentiated and anaplastic thyroid carcinomas. Literature review identified seven CTC cases; 42.8% had TSC association and 42.8% showed locoregional recurrence. Median follow-up of 36\u00a0months showed all patients alive. Common morphologic and immunophenotypic features were consistent; 85.7% exhibited vascular invasion. None harbored common mutations like\n                    <jats:italic>BRAF<\/jats:italic>\n                    p.V600E and\n                    <jats:italic>RAS.<\/jats:italic>\n                    CTC is a distinct, rare thyroid carcinoma often linked to TSC or\n                    <jats:italic>TSC<\/jats:italic>\n                    mutations, characterized by unique morphology and immunophenotype.\n                  <\/jats:p>","DOI":"10.1007\/s00428-025-04380-3","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T06:28:51Z","timestamp":1768026531000},"page":"735-749","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chromophobe thyroid carcinoma: a distinct entity associated with TSC gene alterations"],"prefix":"10.1007","volume":"488","author":[{"given":"Agnes S.","family":"Harahap","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc P.","family":"Pusztaszeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayan","family":"Rammal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Foulkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri E.","family":"Nikiforov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason K.","family":"Wasserman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja R.","family":"Seethala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"key":"4380_CR1","doi-asserted-by":"publisher","first-page":"703","DOI":"10.3803\/EnM.2022.1553","volume":"37","author":"CK Jung","year":"2022","unstructured":"Jung CK, Bychkov A, Kakudo K (2022) Update from the 2022 World Health Organization classification of thyroid tumors: a standardized diagnostic approach. 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Nikiforov owns intellectual property related to the ThyroSeq test and receives royalties through the University of Pittsburgh; he serves as a consultant for Sonic Healthcare USA. All other authors have no conflicts of interest to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}