Objective:

To analyze the clinicopathological characteristics of differentiated high-grade thyroid carcinoma (DHGTC), a newly defined pathological subtype introduced in the 2022 WHO Classification of Thyroid Tumors, and improve understanding among clinicians and pathologists.

Approach:

• Study Design: A retrospective multicenter analysis of 19 patients with DHGTC from three tertiary medical centers.
• Data Collection: Clinical manifestations, histopathological morphology, immunohistochemical findings, and molecular features were analyzed, along with postoperative follow-up data.

Key Findings:

• The cohort included 9 males and 10 females, with a median age of 61 years (range, 24–78 years).
• Tumors exhibited marked invasiveness, with 11 cases involving adjacent structures and 13 cases with lymph node metastasis.
• All cases showed high-grade features, including increased mitotic activity and/or tumor necrosis.
• The Ki-67 proliferation index was ≥10% in all cases, with 10 cases having a Ki-67 index ≥20%, and the highest value reaching 30%.
• BRAF abnormalities were found in 9 cases, including the BRAF V600E mutation.
• Two cases had a TERT promoter mutation, and one case showed abnormal p53 expression.
• During follow-up, 4 patients had recurrence or metastasis, and 2 patients died.

Interpretation:

DHGTC is characterized by aggressive behavior and specific histological and molecular features important for diagnosis and prognostic assessment.

Limitations:

• The study is limited by its small sample size of 19 patients.
• As a retrospective study, it may be subject to selection bias.

Conclusion:

DHGTC is a highly aggressive thyroid malignancy.