{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:06:48Z","timestamp":1792843608978,"version":"4.5.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p>High-grade differentiated thyroid carcinoma is a novel classification defined by elevated mitotic count (MC) of \u22655\/2\u00a0mm<jats:sup>2<\/jats:sup> and\/or tumor necrosis. It may assume a phenotype of papillary thyroid carcinoma, diffuse sclerosing subtype (PTC-DS), and can be termed HGPTC-DS. A detailed clinicopathologic review was conducted on a large series of 18 cases of HGPTC-DS. A control group of 41 PTC-DSs with genomic data was also included. Histologically, HGPTC-DS showed typical features of PTC-DS and HG areas, often exhibiting solid architecture of uniform squamoid cells admixed with tumor necrosis, frequently the comedo type. All HGDTC-DSs had tumor necrosis. The MC was often low (median 1\/2\u00a0mm<jats:sup>2<\/jats:sup>). PTC nuclear features were retained and no nuclear pleomorphism was seen. HGPTC-DS was often subjected to misdiagnosis. Among the 7 external cases, the initial diagnosis was anaplastic carcinoma in 1 and PTC in 5. Compared with PTC-DS, HGPTC-DS was associated with positive resection margin, AJCC eighth edition pT3b and pT4a\/4b disease, gross extrathyroidal extension (ETE), a higher number of regional lymph nodes metastasis, a larger size of nodal metastasis, decreased recurrence-free survival (RFS) and regional recurrence-free survival (<jats:italic toggle=\"yes\">P<\/jats:italic>&lt;0.05). Among the 9 HGPTC-DSs sequenced, 5 harbored <jats:italic toggle=\"yes\">RET<\/jats:italic> fusions, 2 had <jats:italic toggle=\"yes\">STRN::ALK<\/jats:italic> fusion, and 1 had <jats:italic toggle=\"yes\">BRAF<\/jats:italic> p.V600E mutation. In conclusion, HGPTC-DS is a rare high-grade carcinoma characterized by uniform squamoid area with comedo-type tumor necrosis, high pT stage, gross ETE, large volume nodal metastasis, poor RFS, and RRFS. Given its rarity, it may be subjected to misdiagnosis as PTC and anaplastic carcinoma.<\/jats:p>","DOI":"10.1097\/pas.0000000000002371","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T05:08:14Z","timestamp":1743311294000},"page":"481-489","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["High-Grade Papillary Thyroid Carcinoma, Diffuse Sclerosing Subtype"],"prefix":"10.1097","volume":"49","author":[{"given":"Ronald A.","family":"Ghossein","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Scholfield","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok R.","family":"Shaha","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Ganly","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-9835","authenticated-orcid":false,"given":"Bin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"R2-20250416","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/his.14550","article-title":"Primary high-grade non-anaplastic thyroid carcinoma: a retrospective study of 364 cases","volume":"80","author":"Xu","year":"2022","journal-title":"Histopathology"},{"key":"R3-20250416","doi-asserted-by":"crossref","first-page":"100329","DOI":"10.1016\/j.modpat.2023.100329","article-title":"A detailed histologic and molecular assessment of the diffuse sclerosing variant of papillary thyroid carcinoma","volume":"36","author":"Chou","year":"2023","journal-title":"Mod Pathol"},{"key":"R4-20250416","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1007\/s00268-015-3021-9","article-title":"Clinicopathologic features and outcomes in patients with diffuse sclerosing variant of papillary thyroid carcinoma","volume":"39","author":"Akaishi","year":"2015","journal-title":"World J Surg"},{"key":"R5-20250416","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1245\/ASO.2006.03.062","article-title":"Diffuse sclerosing variant of papillary carcinoma of the thyroid: a 35-year comparative study at a single institution","volume":"13","author":"Lam","year":"2006","journal-title":"Ann Surg Oncol"},{"key":"R6-20250416","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1002\/1097-0142(19901201)66:11<2306::AID-CNCR2820661109>3.0.CO;2-P","article-title":"Diffuse sclerosing variant of papillary carcinoma of the thyroid. 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