A Systematic Review of the Diagnostic Role of BRAF V600E Testing in Thyroid Nodules with Atypia of Undetermined Significance

The BRAF V600E mutation is a key molecular marker for malignancy in thyroid nodules showing cytological features of atypia of undetermined significance (AUS). It is strongly associated with papillary thyroid carcinoma (PTC), improves diagnostic accuracy and clinical management stratification, and serves as a significant risk factor of malignancy (ROM) when combined with identifying aggressive features such as lymph node metastases and extra-thyroid extension. This systematic literature review examines the diagnostic role of the BRAF V600E mutation in AUS nodules, emphasizing its integration with cytological evaluation, ultrasound-based risk stratification systems (US-RSS), and cytological subclassification. Selective BRAF testing improves sensitivity and specificity, optimizing resource utilization while reducing unnecessary surgeries. Incorporation of this mutation into multigene classifiers, such as ThyroSeq v3, further supports cost-effective and personalized management strategies for indeterminate thyroid nodules. By combining molecular and imaging data, BRAF V600E testing plays a pivotal role in advancing thyroid cancer diagnosis and treatment. It enhances malignancy risk stratification and facilitates precise clinical decision-making, leading to improved patient outcomes.