Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology.

Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, Livolsi VA, Mandel SJ, Raab SS, Rosai J, Steward DL, Walsh PS, Wilde JI, Zeiger MA, Lanman RB, Haugen BR.

Source

From the Departments of Medicine (E.K.A.) and Pathology (E.S.C.), Brigham and Women's Hospital and Harvard Medical School, Boston; Veracyte, South San Francisco, CA (G.C.K., D.C., J.D., L.F., P.S.W., J.I.W., R.B.L.); the Departments of Pathology (Z.W.B., V.A.L.) and Medicine (S.J.M.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; the Department of Medicine, Ohio State University College of Medicine, Columbus (R.T.K.); the Department of Pathology, University of Washington School of Medicine, Seattle (S.S.R.); Centro Diagnostico Italiano, Milan (J.R.); the Department of Surgery, University of Cincinnati College of Medicine, Cincinnati (D.L.S.); the Department of Surgery, Johns Hopkins University School of Medicine, Baltimore (M.A.Z.); and the Department of Medicine, University of Colorado School of Medicine, Aurora (B.R.H.).

Abstract

Background Approximately 15 to 30% of thyroid nodules evaluated by means of fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment. Methods We performed a 19-month, prospective, multicenter validation study involving 49 clinical sites, 3789 patients, and 4812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. We obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules in this analysis, and its performance was assessed. Results Of the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92% sensitivity; 95% confidence interval [CI], 84 to 97), with a specificity of 52% (95% CI, 44 to 59). The negative predictive values for "atypia (or follicular lesion) of undetermined clinical significance," "follicular neoplasm or lesion suspicious for follicular neoplasm," or "suspicious cytologic findings" were 95%, 94%, and 85%, respectively. Analysis of 7 aspirates with false negative results revealed that 6 had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule. Conclusions These data suggest consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results. (Funded by Veracyte.).