Incremental Diagnostic Value of Cell-Block-Based Targeted BRAF and RAS Testing in TBSRTC Category III–IV Thyroid Nodules: A Single-Center Retrospective Study

Background/Objectives: Risk stratification of thyroid nodules classified as categories III–IV in The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) remains challenging. This study evaluated the incremental diagnostic value of cell-block-based targeted molecular testing beyond TBSRTC cytology within the 2023 TBSRTC and WHO 2022 frameworks.

Methods

This retrospective study included 126 TBSRTC category III–VI thyroid fine-needle aspiration samples. BRAF exon 15 and KRAS/NRAS exons 2–4 were assessed by bidirectional Sanger sequencing; TERT testing was limited to six selected cases. Histopathology was available for 69 nodules, including 59 TBSRTC category III–IV nodules in the primary diagnostic-performance cohort. Logistic regression, ROC analysis, bootstrap correction, repeated stratified five-fold cross-validation, calibration, and exploratory decision curve analysis were performed.