Cytologic features of differentiated high-grade thyroid carcinoma: A multi-institutional study of 40 cases

Differentiated high-grade thyroid carcinoma (DHGTC) is recently recognized by the World Health Organization (WHO) as a subgroup of thyroid carcinomas with high-grade features while retaining the architectural and/or cytologic features of well-differentiated follicular-cell-derived tumors. The cytomorphology of DHGTC is not well documented despite potential implications for patient triage and management.

The pathology archives of six institutions were searched for cases diagnosed on resection as "high-grade thyroid carcinoma" using WHO criteria. The fine-needle aspiration (FNA) cohort represents a 10-year period (2013-2023); all were reviewed to confirm DHGTC classification. The corresponding FNAs were assessed for 32 cytomorphologic features.

Forty cases of DHGTC with prior FNA were identified. The mean patient age was 64.2 years. The average lesion size was 4.9 cm, and the majority demonstrated a TI-RADS score of 4 or 5 (95.2%). Three main high-grade subsets of DHGTC based on corresponding histology included papillary thyroid carcinoma (65%), follicular carcinoma (22.5%), and oncocytic carcinoma (12.5%). Over 97% of FNA cases were classified as Bethesda category IV or above. Approximately 25% of DHGTC showed cytologic features that included marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, or necrosis (p < .05); 68% of DHGTC cases were associated with high-risk molecular alterations. TERT mutations occurred in 41%, of which 89% of these were associated with a second mutation, usually RAS or BRAF p.V600E.

Cytology has a low sensitivity for DHGTC, although a subset of DHGTCs have cytologic features raising the possibility of a high-grade thyroid carcinoma. Other findings include high-risk molecular changes and clinicopathologic features such as older patient age and larger lesion size.