Molecular testing for the management of indeterminate thyroid nodules

Thyroid nodules are extremely common with a prevalence of up to 70% in the general population. While the majority of these are benign, 5-10% harbor a malignancy. Fine-needle aspiration has been widely implemented to stratify the cancer risk of thyroid nodules. Standardized diagnoses using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) have aided in the triaging of nodules. While many cases are categorized with a definite diagnosis of benign (Bethesda II) or malignant (Bethesda VI) results, approximately 25% of cases are diagnosed as atypia of undetermined significance (AUS) (Bethesda III) or follicular neoplasm (Bethesda IV). These cytological categories imply an intermediate risk of malignancy ranging from 16 to 48%. These nodules, collectively defined as indeterminate thyroid nodules, pose diagnostic and management challenges. In recent years, several commercial molecular testing (MT) methods have become available to improve risk stratification, successfully helping to reduce unnecessary surgeries. In this review, we provide an overview of MT methods, present practical guidance on interpreting test results, and conclude with a discussion on future directions in the field.