Trends in thyroid Bethesda category III in the era of molecular testing: a single-center study

Molecular testing is increasingly integrated into the management of indeterminate thyroid fine-needle aspiration (FNA) diagnoses, particularly The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III. However, it remains unclear how increasing test availability has affected cytopathologists' use of this category and whether its expansion risks incorporating nodules that may not warrant surgery, particularly following the 2023 TBSRTC nomenclature updates.

We retrospectively queried all in-house thyroid FNAs from 2018 to 2024, assessing temporal trends in TBSRTC category distribution, with focused analysis of TBSRTC III cases and associated parameters including ThyroSeq utilization, atypia of undetermined significance:malignant ratio, and risk of malignancy (ROM).

From 2018 to 2024, TBSRTC III interpretations increased significantly (6%-26% of FNAs), accompanied by increased ThyroSeq utilization in this category (5%-75%) and atypia of undetermined significance:malignant ratios (1.0-4.5). Meanwhile, the proportion of TBSRTC III cases undergoing surgery declined (40%-26%). Surgical selection became strongly influenced by molecular results, with 71% of ThyroSeq-positive TBSRTC III nodules undergoing resection in 2024 compared with only 3% of ThyroSeq-negative nodules. Increased use of TBSRTC III occurred primarily at the expense of category II, while categories IV-VI remained stable. ROM was not statistically different with and without molecular testing. Molecular changes were consistent with published ThyroSeq cohorts.

These findings suggest that increased ThyroSeq utilization is associated with increased use of TBSRTC III and more selective surgical management without altering ROM or increasing the inclusion of lesions less likely to require surgery.