Value of Molecular Tests in Cytologically Indeterminate Lesions of Thyroid

Context.-Fine-needle aspiration has been the initial step in the workup of thyroid nodular lesions and has successfully reduced the number of unnecessary surgeries and improved preoperative malignancy detection. However, up to one-third of cases fall in the diagnostically "indeterminate group," which poses a patient-management challenge. Objective.-To review the characteristics of molecular tests useful for stratifying the malignancy risk of indeterminate thyroid lesions, including their advantages and limitations. Data sources.-PubMed. Conclusions.-Molecular tests are useful for triage of indeterminate thyroid nodules initially diagnosed by using fine-needle aspiration. Immunocytochemistry is readily available with the shortest turnaround time among the molecular tests but suffers from poor reproducibility and low interpretation concordance. Gene mutation analysis is superior in detecting malignancies as a rule-in test, despite low specificity. Next-generation sequencing seems promising but needs more validations before widespread use. Gene expression profiling is more suitable for detecting benign lesions as a rule-out test to avoid unnecessary surgeries but is not reliable in excluding malignancies. MicroRNA profiling has great potential for both risk stratification and predicting prognosis but is limited by significant variations in sensitivity and specificity. Although many questions still need to be answered, taken together, molecular tests are a promising option for classifying cytologically indeterminate thyroid nodular lesions.