Molecular Testing in Indeterminate Thyroid Nodules

PODCAST SUMMARY: Fine-needle aspiration yields indeterminate cytopathology (Bethesda III/IV) in up to 30% of thyroid nodules, creating clinical management dilemmas between diagnostic hemithyroidectomy and conservative surveillance. Modern molecular testing panels utilize next-generation sequencing and gene expression classifiers to profile somatic mutations (BRAF, RAS), gene fusions (RET/PTC, PAX8-PPARG), and copy number alterations. High negative predictive value (rule-out) testing allows low-risk nodules to avoid unneeded diagnostic surgery, whereas high positive predictive value (rule-in) alterations, particularly TERT promoter co-mutations, signal high-risk aggressive malignancies requiring complete resection. Integrating molecular risk stratification optimizes individualized surgical planning while curbing overtreatment.