Diagnostic Challenges, Prognostic Assessment, and Treatment Strategies in High-Grade Differentiated Thyroid Carcinoma.

High-grade differentiated thyroid carcinoma (HGDTC) is a recently codified entity in the 2022 World Health Organization Classification of Endocrine Tumors, defined by a mitotic count of ≥5 mitoses per 2 mm² and/or tumor necrosis in a carcinoma that retains papillary, follicular, or oncocytic differentiation without anaplastic morphology. Although uncommon, HGDTC presents significant diagnostic and therapeutic challenges. This review summarizes current evidence regarding histopathologic recognition, molecular features, prognostic determinants, and evolving treatment paradigms. Particular attention is given to pattern-specific pitfalls such as high-grade papillary thyroid carcinoma, the diffuse sclerosing subtype, and the prognostic influence of the invasion phenotype (encapsulated versus infiltrative). Subcentimeter papillary carcinomas exhibiting increased mitotic activity alone should not be overinterpreted as HGDTC. An integrated, stepwise approach is proposed to enhance diagnostic reproducibility, refine risk stratification, and optimize multidisciplinary management in clinical practice.