Fine Needle Aspiration: Role of Molecular Testing

Abstract

Fine needle aspiration (FNA) findings of thyroid nodules are interpreted in light of the pretest probability of malignancy. The Bethesda System of Reporting Thyroid Cytopathology (BSRTC) standardizes the reporting of results and associates an evidence-based risk of malignancy (ROM) for each category. Clinical action is taken based on these ROM projections. Surgical intervention is indicated for B VI (malignant) lesions and follow-up is generally suggested for B II (Benign) nodules. Management is less certain for the 20–30% of cases that are indeterminate. This chapter will discuss approaches to further define the ROM of indeterminate nodules. Techniques range from immunochemistry staining of cytopathology using markers of thyroid malignancy or seeking specific molecular markers of thyroid malignancy (genetic mutations and rearrangements) which because of their high positive predictive value (PPV) are considered “Rule-In tests.” Another approach uses molecular markers to identify benign thyroid tissue, providing a high negative predictive value (NPV). An alternative method to derive a high NPV is to seek a multitude of common and rarely associated genetic markers of malignancy which if absent, rule out the likelihood of malignancy in the indeterminate nodule. The reader will review a detailed description of the markers used, the performance of these techniques in trials and actual practice, and some suggestions on how to utilize these tests to predict the ROM of indeterminate nodules to guide clinical decision making.