Clinicopathological, proliferative, molecular, and prognostic characteristics of differentiated high-grade thyroid carcinoma: a multicenter retrospective study.

Objective: Differentiated high-grade thyroid carcinoma (DHGTC) is a newly defined pathological subtype introduced in the 5th edition of the World Health Organization (WHO) Classification of Thyroid Tumors in 2022. This study aimed to analyze its clinicopathological characteristics and improve the understanding of this entity among clinicians and pathologists. Methods: A total of 19 patients with DHGTC from three tertiary medical centers were retrospectively included. Clinical manifestations, histopathological morphology, immunohistochemical findings, and molecular pathological features were analyzed. Postoperative follow-up data were reviewed to evaluate prognosis, and relevant literature was also reviewed. Results: Among the 19 patients, 9 were male and 10 were female, with a median age of 61 years (range, 24-78 years). The tumors showed marked invasiveness, with 11 cases involving adjacent structures and 13 cases presenting with lymph node metastasis. All cases exhibited high-grade pathological features, characterized by increased mitotic activity and/or tumor necrosis. The Ki-67 proliferation index was ≥10% in all cases, including 10 cases with a Ki-67 index ≥20%, with the highest value reaching 30%. BRAF abnormalities were identified in 9 cases by molecular testing and/or immunohistochemistry, including aberrant immunohistochemical expression and/or molecular confirmation of the BRAF V600E mutation. In addition, two cases harbored a TERT promoter mutation, and one case showed abnormal p53 expression. During follow-up, 4 patients developed recurrence or metastasis, and 2 patients died. Conclusions: DHGTC is a highly aggressive thyroid malignancy with a poor prognostic tendency. Increased mitotic activity, tumor necrosis, elevated Ki-67 index, and molecular abnormalities such as BRAF alterations are important for diagnosis and prognostic assessment.