Molecular diagnostic testing and the indeterminate thyroid nodule

Abstract

Purpose of review: To summarize the latest developments in the use of molecular diagnostic testing in cytologically indeterminate thyroid nodules.

Recent findings: The majority of nodules with fine needle aspiration biopsy (FNAB) results that are classified as indeterminate (i.e., atypia of undetermined significance/lesion of undetermined significance, follicular neoplasm, and suspicious for malignancy) are histologically benign. Improvements in diagnostic discrimination can potentially be achieved with immunocytochemical analysis for candidate protein markers such as galectin-3, or analysis of differential microRNA expression patterns although larger prospective validation studies are still needed. After large-scale gene expression analysis, a marker panel was selected with the goal of optimizing the negative predictive value, and in indeterminate nodules, the panel may be helpful in lowering but not eliminating the risk of cancer. Another panel composed of gene mutations and rearrangements associated with thyroid cancer can improve the specificity and positive predictive value of preoperative FNAB, and better identify cytologically indeterminate nodules with a high risk of cancer.

Summary: Molecular diagnostic testing improves preoperative risk stratification for nodules that have indeterminate FNAB results. Although currently available tests do not yet have the sensitivity to reliably exclude malignancy altogether, improvements in specificity can be used to guide the extent of initial surgery and clinical management.