Objective: The Afirma gene expression classifier (GEC) is a molecular test to further classify indeterminate fine-needle aspiration (FNA) as benign or suspicious for malignancy. Study Design: A total of 158 FNAs with Bethesda category III/IV cytology were sent for an Afirma GEC test. We correlated the Afirma GEC results with surgical outcome and also compared the data after Afirma's implementation with the data before. Results: Among the 158 FNAs, the Afirma result was benign in 63 (40%), suspicious in 85 (54%) and unsatisfactory in 10 (6%). In total, 73 (86%) suspicious Afirma cases had surgery and 28 (38%) showed carcinoma. In contrast, only 8 (13%) benign Afirma cases had surgery and all of them were benign. The sensitivity, specificity, negative predictive value and positive predictive value (PPV) of Afirma were 100, 15, 100 and 38%, respectively. The PPV was 20% in cases with follicular lesion of undetermined significance, but was 50% in cases suspicious for follicular neoplasm (SFN). The surgical excisional rate was significantly decreased in SFN cases after the Afirma test. Conclusions: The Afirma GEC is useful for further risk stratifying SFN cases.

1.
Vander JB, Gaston EA, Dawber TR: The significance of nontoxic thyroid nodules: final report of a 15-year study of the incidence of thyroid malignancy. Ann Intern Med 1968;69:537-540.
2.
Tunbridge WM, Evered DC, Hall R, et al: The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977;7:481-493.
3.
Tan GH, Gharib H: Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 1997;126:226-231.
4.
Guth S, Theune U, Aberle J, Galach A, Bamberger CM: Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest 2009;39:699-706.
5.
Caruso DR, Mazzaferri EL: Fine needle aspiration biopsy in the management of thyroid nodules. Endocrinologist 1991;1:194-202.
6.
Cooper DS, Doherty GM, Haugen BR, et al: Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-1214.
7.
Gharib H, Papini E, Paschke R, et al: American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. J Endocrinol Invest 2010;33:1-50.
8.
Gharib H, Goellner JR: Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med 1993;118:282-289.
9.
Cibas ES, Ali SZ: The Bethesda System for reporting thyroid cytopathology. Am J Clin Pathol 2009;132:658-665.
10.
Moses W, Weng J, Sansano I, et al: Molecular testing for somatic mutations improves the accuracy of thyroid fine needle aspiration biopsy. World J Surg 2010;34:2589-2594.
11.
Ferraz C, Eszlinger M, Paschke R: Current state and future perspective of molecular diagnosis of fine-needle aspiration biopsy of thyroid nodules. J Clin Endocrinol Metab 2011;96:2016-2026.
12.
Nikiforov YE, Ohori NP, Hodak SP, et al: Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1,056 FNA samples. J Clin Endocrinol Metab 2011;96:3390-3397.
13.
Nikiforov YE, Steward DL, Robinson-Smith TM, et al: Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab 2009;94:2092-2098.
14.
Chudova D, Wilde JI, Wang ET, et al: Molecular classification of thyroid nodules using high-dimensionality genomic data. J Clin Endocrinol Metab 2010;95:5296-5304.
15.
Alexander EK, Kennedy GC, Baloch ZW, et al: Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med 2012;367:705-715.
16.
Alexander EK, Schorr M, Klopper J, et al: Multicenter clinical experience with the Afirma gene expression classifier. J Clin Endocrinol Metab 2014;99:119-125.
17.
Harrell RM, Bimston DN: Surgical utility of Afirma: effects of high cancer prevalence and oncocytic cell types in patients with indeterminate thyroid cytology. Endocr Pract 2014;20:364-369.
18.
Faquin WC: Can a gene-expression classifier with high negative predictive value solve the indeterminate thyroid fine-needle aspiration dilemma? Cancer Cytopathol 2013;121:116-119.
19.
Yang SE, Sullivan PS, Zhang J, Govind R, Levin MR, Rao JY, Moatamed NA: Has Afirma gene expression classifier testing refined the indeterminate thyroid category in cytology? Cancer Cytopathol 2016;124:100-109.
20.
Angell TE, Frates MC, Medici M, Liu X, Kwong N, Cibas ES, Kim MI, Marqusee E: Afirma benign thyroid nodules show similar growth to cytologically benign nodules during follow-up. J Clin Endocrinol Metab 2015;100:E1477-E1483.
21.
Sipos JA, Blevins TC, Shea HC, Duick DS, Lakhian SK, Michael BE, Thomas MJ, Sosa JA: Long-term non-operative rate of thyroid nodules with benign results on the Afirma gene expression classifier. Endocr Pract 2016, Epub ahead of print.
22.
Singer J, Hanna JW, Visaria J, Gu T, McCoy M, Kloos RT: Impact of a gene expression classifier on the long-term management of patients with cytologically indeterminate thyroid nodules. Curr Med Res Opin 2016;2016:1-8.
23.
Yassa L, Cibas ES, Benson CB, et al: Long-term assessment of a multidisciplinary approach to thyroid nodule diagnostic evaluation. Cancer 2007;111:508-516.
24.
Nayar R, Ivanovic M: The indeterminate thyroid fine-needle aspiration: experience from an academic center using terminology similar to that proposed in the 2007 National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. Cancer 2009;117:195-202.
25.
Lastra RR, Pramick MR, Crammer CJ, LiVolsi VA, Baloch ZW: Implications of a suspicious Afirma test result in thyroid fine-needle aspiration cytology: an institutional experience. Cancer Cytopathol 2014;122:737-744.
26.
McIver B, Castro MR, Morris JC, et al: An independent study of a gene expression classifier (Afirma) in the evaluation of cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab 2014;99:4069-4077.
27.
Brauner E, Holmes BJ, Krane JF, Nishino M, Zurakowski D, Hennessey JV, Faquin WC, Parangi S: Performance of the Afirma gene expression classifier in Hürthle cell thyroid nodules differs from other indeterminate thyroid nodules. Thyroid 2015;25:789-796.
28.
Celik B, Whetsell CR, Nassar A: Afirma GEC and thyroid lesions: an institutional experience. Diagn Cytopathol 2015;43:966-970.
29.
Li H, Robinson KA, Anton B, Saldanha IJ, Ladenson PW: Cost-effectiveness of a novel molecular test for cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab 2011;96:E1719-E1726.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.