High-grade papillary thyroid carcinoma, diffuse sclerosing subtype: A series of 18 cases detailing the pathologic features, potential for misdiagnosis, and aggressive clinical behavior Journal Article

  

Authors:	Ghossein, R. A.; Scholfield, D. W.; Qin, H.; Shaha, A. R.; Ganly, I.; Xu, B.
Article Title:	High-grade papillary thyroid carcinoma, diffuse sclerosing subtype: A series of 18 cases detailing the pathologic features, potential for misdiagnosis, and aggressive clinical behavior
Abstract:	High-grade differentiated thyroid carcinoma is a novel classification defined by elevated mitotic count (MC) of ≥5/2 mm2 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 mm2). 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 (P<0.05). Among the 9 HGPTC-DSs sequenced, 5 harbored RET fusions, 2 had STRN::ALK fusion, and 1 had BRAF 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. Copyright © 2025 Wolters Kluwer Health, Inc.
Keywords:	adolescent; adult; child; clinical article; controlled study; human tissue; school child; aged; young adult; clinical feature; histopathology; cancer staging; lymph node metastasis; gene; distant metastasis; radioactive iodine; gene fusion; diagnostic error; cell nucleus; thyroid papillary carcinoma; protein ret; b raf kinase; recurrence free survival; anaplastic lymphoma kinase; comedo; tumor necrosis; anaplastic thyroid carcinoma; extranodal extension; human; male; female; article; high grade differentiated thyroid carcinoma; involved margin; diffuse sclerosing subtype; high grade papillary thyroid carcinoma; high grade papillary thyroid carcinoma diffuse sclerosing subtype; strn gene
Journal Title:	American Journal of Surgical Pathology
Volume:	49
Issue:	5
ISSN:	0147-5185
Publisher:	Lippincott Williams & Wilkins
Date Published:	2025-05-01
Start Page:	481
End Page:	489
Language:	English
DOI:	10.1097/pas.0000000000002371
PUBMED:	40143646
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105002423398&doi=10.1097%2fPAS.0000000000002371&partnerID=40&md5=953a3de241856aa612dba079c04cf96e
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Bin Xu -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/224551