The role of molecular genetics in the presurgical management of thyroid nodules

Fine-needle aspiration (FNA) is an important diagnostic tool for the evaluation of thyroid nodules. However, in almost ¼ of all nodules submitted to FNA cytology is indeterminate. Since the majority of genetic alterations in thyroid cancer have been identified, the use of molecular testing platforms has been endorsed by American Thyroid Association for management of indeterminate nodules.

Several commercial tests were based on mRNA expression of FNA samples (Afirma®, Veracyte, South San Francisco, CA, USA) while others detect DNA alterations (ThyroSeq, UPMC, Pittsburgh, PA, USA). Noncommercial tests detect limited number of point mutations or re-arrangements (gene panels). Literature study included a Pubmed research for adult original studies from 2003 to 2020, focusing on terms such as "molecular tests," "nodules with indeterminate AUS/FLUS and FN/SFN cytology."

Gene expression profile tests serve as "rule out" tests due to their high negative predictive value and perform better in a setting of low cancer pretest probability. Genetic alteration platforms display high positive predictive value and serve as rather "rule in" tests but their diagnostic accuracy is hampered either because a small proportion of nodules does not harbor any of these alterations targeted (gene panels) or because commonly identified RAS mutations can also be found in benign nodules.

Next generation sequencing development and incorporation of other genetic markers such as miRNA can improve diagnostic accuracy of molecular tests.