High-Grade Papillary Thyroid Carcinoma, Diffuse Sclerosing Subtype
Year: 2025
Type: article
Study design: Observational Study
Abstract: High-grade differentiated thyroid carcinoma is a novel classification defined by elevated mitotic count (MC) of ≥5/2 mm 2 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 mm 2 ). 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.
Authors: Ronald A. Ghossein, Daniel W. Scholfield, Howard Qin, Ashok R. Shaha, Ian Ganly, Bin Xu
Institution: Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Cancer Institute
Award: Cancer Center Support Grant
OpenAlex ID: W4408921552
