Objective: Of the 6 categories in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category has received the most attention. The objectives of this study were to review the use of the AUS/FLUS category in recent studies, to search for likely sources of the variability in its use, and to address possible methods for improvement. Study Design: A PubMed search was performed to retrieve peer-reviewed articles that have comprehensively detailed the incidence and outcome of AUS/FLUS and other BSRTC categories. Related thyroid cytology articles on the BSRTC were also included. Results: Recent series that reported experiences with the BSRTC categories showed that the AUS/FLUS category exhibited a marked variability in incidence (0.7–18%) and malignant outcome (6–48%) in resection specimens. Review of the literature revealed institutional differences in technical aspects, interpretation and application of criteria, analysis of outcome data, and clinicopathologic interactions. Conclusions: A heightened awareness of technical issues, diagnostic borders of AUS/FLUS, and clinical management may aid in diagnostic refinement and help avoid overuse of this category.

Keywords:
Thyroid, Atypia of undetermined significance/follicular lesion of undetermined significance, Variability, Bethesda System, Outcome
1.
Wang HH: Reporting thyroid fine-needle aspiration: literature review and a proposal. Diagn Cytopathol 2006;34:67–76.
2.
Cibas ES, Alexander EK, Benson CB, et al: Indications for thyroid FNA and pre-FNA requirements: a synopsis of the National Cancer Institute Thyroid Fine-needle Aspiration State of the Science Conference. Diagn Cytopathol 2008;36:390–399.
3.
Ljung BE, Langer J, Mazzaferri EL, Oertel YC, Wells SA, Waisman J: Training, credentialing and re-credentialing for the performance of a thyroid FNA: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008;36:400–406.
4.
Pitman MB, Abele J, Ali SZ, et al: Techniques for thyroid FNA: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008;36:407–424.
5.
Baloch ZW, LiVolsi VA, Asa SL, et al: Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008;36:425–437.
6.
Filie AC, Asa SL, Geisinger KR, et al: Utilization of ancillary studies in thyroid fine needle aspirates: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008;36:438–441.
7.
Layfield LJ, Abrams J, Cochand-Priollet B, et al: Post-thyroid FNA testing and treatment options: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008;36:442–448.
8.
Krane JF, Nayar R, Renshaw AA: Atypia of undetermined significance/follicular lesion of undetermined significance; in Ali SZ, Cibas ES (eds): The Bethesda System for Reporting Thyroid Cytopathology: Definitions, Criteria and Explanatory notes. New York, Springer, 2010, pp 37–49.
9.
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 Cytopathol 2009;117:195–202.
10.
Theoharis CG, Schofield KM, Hammers L, Udelsman R, Chhieng DC: The Bethesda thyroid fine-needle aspiration classification system: year 1 at an academic institution. Thyroid 2009;19:1215–1223.
11.
Marchevsky AM, Walts AE, Bose S, et al: Evidence-based evaluation of the risks of malignancy predicted by thyroid fine-needle aspiration biopsies. Diagn Cytopathol 2010;38:252–259.
12.
Jo VY, Stelow EB, Dustin SM, Hanley KZ: Malignancy risk for fine-needle aspiration of thyroid lesions according to the Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol 2010;134:450–456.
13.
Renshaw AA: Should ‘atypical follicular cells’ in thyroid fine-needle aspirates be subclassified? Cancer Cytopathol 2010;118:186–189.
14.
Luu MH, Fischer AH, Pisharodi L, Owens CL: Improved preoperative definitive diagnosis of papillary thyroid carcinoma in FNAs prepared with both ThinPrep and conventional smears compared with FNAs prepared with ThinPrep alone. Cancer Cytopathol 2011;119:68–73.
15.
Layfield LJ, Morton MJ, Cramer HM, Hirschowitz S: Implications of the proposed thyroid fine-needle aspiration category of ‘follicular lesion of undetermined significance’: a five-year multi-institutional analysis. Diagn Cytopathol 2009;37:710–714.
16.
Shi Y, Ding X, Klein M, et al: Thyroid fine-needle aspiration with atypia of undetermined significance: a necessary or optional category? Cancer 2009;117:298–304.
17.
Ohori NP, Nikiforova MM, Schoedel KE, et al: Contribution of molecular testing to thyroid fine-needle aspiration cytology of ‘follicular lesion of undetermined significance/atypia of undetermined significance’. Cancer Cytopathol 2010;118:17–23.
18.
Faquin WC, Baloch ZW: Fine-needle aspiration of follicular patterned lesions of the thyroid: diagnosis, management, and follow-up according to National Cancer Institute (NCI) recommendations. Diagn Cytopathol 2010;38:731–739.
19.
VanderLaan PA, Marqusee E, Krane JF: Clinical outcome for atypia of undetermined significance in thyroid fine-needle aspirations. Am J Clin Pathol 2011;135:770–775.
20.
Raab SS, Vrbin CM, Grzybicki DM, et al: Errors in thyroid gland fine-needle aspiration. Am J Clin Pathol 2006;125:873–882.
21.
Bongiovanni M, Krane JF, Cibas ES, Faquin WC: The atypical thyroid fine-needle apriation: past, present, and future. Cancer Cytopathol 2011, DOI: 10.1002/cncy.20178.
22.
Elsheikh TM, Asa SL, Chan JK, et al: Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol 2008;130:736–744.
23.
Lloyd RV, Erickson LA, Casey MB, et al: Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol 2004;28:1336–1340.
24.
Wu HH, Jones JN, Osman J: Fine-needle aspiration cytology of the thyroid: ten years experience in a community teaching hospital. Diagn Cytopathol 2006;34:93–96.
25.
Sangalli G, Serio G, Zampatti C, et al: Fine needle aspiration cytology of the thyroid: a comparison of 5,469 cytological and final histological diagnoses. Cytopathology 2006;17,245–250.
26.
Renshaw AA, Gould EW: Why there is the tendency to ‘overdiagnose’ the follicular variant of papillary thyroid carcinoma. Am J Clin Pathol 2002;117:19–21.
27.
Cramer JD, Fu P, Harth KC, Margevicius S, Wilhelm SM: Analysis of the rising incidence of thyroid cancer using the surveillance, epidemiology and end results national cancer data registry. Surgery 2010;148:1147–1153.
28.
Morris LG, Myssiorek D: Improved detection does not fully explain the rising incidence of well-differentiated thyroid cancer: a population-based analysis. Am J Surg 2010;200:454–461.
29.
Renshaw A: An estimate of risk of malignancy for a benign diagnosis in thyroid fine-needle aspirates. Cancer Cytopathol 2010;118:190–195.
30.
Lewis CM, Chang KP, Pitman M, Faquin WC, Randolph GW: Thyroid fine-needle aspiration biopsy: variability in reporting. Thyroid 2009;19:717–723.
31.
Abele JS, Levine RA: Diagnostic criteria and risk-adapted approach to indeterminate thyroid cytodiagnosis. Cancer Cytopathol 2010;118:415–422.
32.
Wang HH, Filie AC, Clark DP, Powers CN: Suspicious for malignancy; in Ali SZ, Cibas ES (eds): The Bethesda System for Reporting Thyroid Cytopathology: Definitions, Criteria and Explanatory Notes. New York, Springer, 2010, pp 75–89.
33.
Ogilvie JB, Patel KN, Heller KS: Impact of the 2009 American Thyroid Association guidelines on the choice of operation for well-differentiated thyroid microcarcinomas. Surgery 2010;148:1222–1227.
34.
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.
© 2011 S. Karger AG, Basel
2011
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.