Thyroid Nodules with Indeterminate Cytology

To the Editor: Alexander et al. (Aug. 23 issue)1 report findings from a prospective, multicenter gene-expression classifier validation study that raises several questions. For the 265 indeterminate fine-needle aspirates they tested, the geneexpression classifier had a sensitivity of 92%, a specificity of 52%, a positive predictive value of 47%, and a negative predictive value of 93%. Why the observed reduction in the performance of the gene-expression classifier, which was reported in their earlier study to have a sensitivity of 100% and a specificity of 73.3%?2 With a high negative predictive value and a low positive predictive value, the gene-expression classifier is useful as an adjunct to fine-needle aspiration biopsy for diagnosing indeterminate nodules as benign and potentially avoiding diagnostic thyroid surgery.3 However, the appropriate management of nodules diagnosed as “suspicious” (positive predictive value, 47%) according to the results of gene-expression classification is less obvious. Unfortunately, the gene-expression classifier does not have a positive predictive value that will allow us, as surgeons, to confidently plan an operation tailored to treat thyroid cancer (i.e., total thyroidectomy and central neck dissection). When considering the clinical and economic effect of a gene-expression classifier on the management of indeterminate nodules, avoiding thyroid surgery is not appropriate as the sole end point, and future studies must carefully evaluate the treatments and outcomes of all patients who undergo such testing.