How to use molecular testing results to guide surgery

Abstract

Multiple genetic mutations have been found to be associated with thyroid cancer, and molecular testing of thyroid nodule fine-needle aspiration (FNA) specimens has been proposed as an adjunct to the cytologic diagnosis. The purpose of this review is to examine how molecular testing of FNAs could be used to guide surgical decision-making. B-type RAF kinase mutations in papillary thyroid cancer have been found to be associated with extrathyroidal extension, lymph node metastases, and advanced stage in two meta-analyses that are based largely on retrospective data. Testing for a panel of gene mutations has been found to have high specificity and positive predictive value, whereas microarray testing using a commercially available gene-expression classifier has been found to have high sensitivity and negative predictive value for the diagnosis of malignancy in cytologically indeterminate FNAs. Although there is no consensus regarding the use of such tests, they have already started to change clinical practice. Molecular testing of FNA specimens may help to avoid diagnostic thyroidectomy or may help in deciding the extent of surgery in a patient with an indeterminate FNA biopsy. The use of these tests is currently undergoing review by a task force within the American Thyroid Association.