Fine-Needle Aspiration and Molecular Analysis

Abstract Indeterminate cytopathology has been a major clinical challenge in the identification of malignancy in thyroid nodules by fine-needle aspiration. Diagnostic lobectomy has long been the standard of care to establish a definitive diagnosis but has led to over- or undertreatment for most patients. Advances in the understanding of thyroid carcinogenesis have revealed many of the genetic drivers of thyroid cancer, along with the molecular basis of distinct subtypes and behaviors. Molecular diagnostics that leverage these markers are now widely available and aid in the preoperative stratification of malignancy risk. Although most commercially available tests initially differed in their use of genotyping or gene expression analysis, evolution of the technology has led to the combinatorial use of methods to optimize positive and negative predictive values. Validation studies in a wide number of clinical settings confirm molecular tools improve our ability to triage patients for observation or surgery, as well as help define the extent of surgery when necessary. Optimal application of these tests requires appreciating the local prevalence of malignancy for Bethesda III/IV/V categories, along with practical considerations of insurance coverage and cost. These technologies are becoming increasingly prevalent and are already being applied beyond indeterminate cytopathology to aid in diagnosis, prognosis, selection of therapies, and the development of novel therapeutics.