Molecular testing in indeterminate thyroid nodules: an additional tool for clinical decision-making

Thyroid nodules are commonly encountered in clinical practice, affecting up to 50% of the population. The large majority of thyroid lumps are benign incidental findings detected by imaging, while approximately 5-15% harbor malignancy. For a target patient's care, it is of paramount importance to identify and treat thyroid malignancy, while preventing unnecessary invasive surgery in patients with benign lesions. Although fine needle aspiration (FNA) associated with cytological examination provides malignant risk information, 20-30% of diagnoses fall into the "indeterminate thyroid nodule" (ITN) category. ITN clinical management remains a challenging issue for physicians since the ITN risk of malignancy varies from 5% to 40% and most thyroid nodules undergo overtreatment with surgery procedures. ITN molecular testing may better define malignant risk in the single nodule and is able to discriminate with accuracy benign from malignant nodules. Nowadays there are different technologies and different molecular panels, each with its own specificity, sensitivity and predictive values. In view of widespread introduction of molecular testing, some outstanding questions remain and are addressed in the present review such as the presence of molecular panels acting as "rule in" or "rule out" tools, the effective impact of testing results in the clinical decision-making process, and the prohibitive cost of commercial assays associated with the lack of test reimbursement in national health systems.