Abstract
INTRODUCTION: Extrathyroidal extension (ETE) is a critical prognostic factor influencing treatment decisions in papillary thyroid carcinoma (PTC). While ultrasonography (US) is widely used for preoperative ETE assessment, its diagnostic accuracy varies across anatomical sites and tumor characteristics. This study evaluates the performance of US in predicting pathologic ETE in PTC, focusing on strap muscle, tracheal, and recurrent laryngeal nerve (RLN) invasion, stratified by tumor size, histopathology, and molecular profile. METHODS: A retrospective analysis of surgically treated PTC patients was conducted. Sonographic features assessed included capsular disruption, strap muscle replacement, tumor-trachea angle, and RLN protrusion into the tracheoesophageal groove (TEG). Diagnostic performance was measured via sensitivity, specificity, positive (PPV) and negative predictive values (NPV), with subgroup analyses based on tumor size, histologic risk, and genetic alterations. RESULTS: In total, 1625 patients were analyzed. For strap muscle invasion, the feature of strap muscle replacement demonstrated high specificity (96.6%) and a PPV that increased with tumor size, reaching 75.9% in tumors > 3 cm. This PPV was further elevated to 87.5% in tumors with high-risk BRAF + TERT co-mutations. For tracheal invasion, an obtuse tumor-trachea angle was the most accurate predictor, maintaining a high PPV across all tumor sizes (85.7% in ≤ 1 cm tumors). RLN involvement was best predicted by protrusion into the tracheoesophageal groove, which showed high sensitivity (83.3%) but a modest PPV (25.6%). Molecular stratification revealed that BRAF + TERT co-mutations were consistently associated with a higher PPV for ETE across all sites, despite a lower sensitivity. CONCLUSION: Sonographic features like strap muscle replacement and obtuse tumor-trachea angles are highly specific for ETE and should strongly guide surgical planning. The assessment of RLN invasion, while sensitive, requires caution due to a high false-positive rate. Molecular profiling, particularly for BRAF + TERT co-mutations, significantly enhances risk stratification, underscoring the value of a tailored, multi-parameter preoperative evaluation.