Objective: The Bethesda System for Reporting Thyroid Cytopathology is now widely used as the standard reporting system for fine-needle aspiration cytology (FNAC). Recently, several studies have attempted to subcategorize the atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) category. We aimed to analyze the significance of a subcategory of AUS/FLUS showing both cytologic and architectural atypia (AUS/FLUS-C&A). Study Design: From April 2011 to May 2014, 18,091 patients underwent FNAC at Samsung Medical Center. For those patients we analyzed the clinical significance of the subcategory AUS/FLUS-C&A. Results: One hundred and sixty-three patients were diagnosed as AUS/FLUS-C&A. Of 71 cases with subsequent histologic confirmation, 47 (66.2%) were diagnosed with papillary thyroid carcinoma (PTC). Of the 47 PTC cases, 32 (68.1%) were follicular variant-PTC. A significant difference in the PTC rate (58.3 vs. 82.6%) and PTC size (average: 1.8 and 0.9 cm) was noted between circumscribed lesions and infiltrative lesions on ultrasonography. Conclusion: We demonstrated that the subcategory of AUS/FLUS-C&A has considerable clinical implications and one should be aware of the cytological and ultrasonographic features.

Keywords:
Atypia of undetermined significance, Follicular lesion of undetermined significance, Thyroid, Fine-needle aspiration, Papillary thyroid carcinoma
1.
Ali SZ Cibas ES: The Bethesda System for Reporting Thyroid Cytopathology. New York, Springer, 2010.
2.
Bongiovanni M, Krane JF, Cibas ES, Faquin WC: The atypical thyroid fine-needle aspiration: past, present, and future. Cancer Cytopathol 2012;120:73-86.
3.
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.
4.
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.
5.
Renshaw AA, Gould EW: Should ‘indeterminate' diagnoses be used for thyroid fine-needle aspirates of nodules smaller than 1 cm? Arch Pathol Lab Med 2013;137:1627-1629.
6.
Ohori NP, Nikiforova MN, Schoedel KE, LeBeau SO, Hodak SP, Seethala RR, Carty SE, Ogilvie JB, Yip L, Nikiforov YE: 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.
7.
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.
8.
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.
9.
Rabaglia JL, Kabbani W, Wallace L, Holt S, Watumull L, Pruitt J, Snyder WH, Nwariaku FE: Effect of the Bethesda System for Reporting Thyroid Cytopathology on thyroidectomy rates and malignancy risk in cytologically indeterminate lesions. Surgery 2010;148:1267-1272; discussion 1272-1263.
10.
VanderLaan PA, Marqusee E, Krane JF: Clinical outcome for atypia of undetermined significance in thyroid fine-needle aspirations: should repeated FNA be the preferred initial approach? Am J Clin Pathol 2011;135:770-775.
11.
Olson MT, Clark DP, Erozan YS, Ali SZ: Spectrum of risk of malignancy in subcategories of ‘atypia of undetermined significance'. Acta Cytol 2011;55:518-525.
12.
Hyeon J, Ahn S, Shin JH, Oh YL: The prediction of malignant risk in the category ‘atypia of undetermined significance/follicular lesion of undetermined significance' of the Bethesda System for Reporting Thyroid Cytopathology using subcategorization and BRAF mutation results. Cancer Cytopathol 2014;122:368-376.
13.
Park HJ, Moon JH, Yom CK, Kim KH, Choi JY, Choi SI, Ahn SH, Jeong WJ, Lee WW, Park SY: Thyroid ‘atypia of undetermined significance' with nuclear atypia has high rates of malignancy and BRAF mutation. Cancer Cytopathol 2014;122:512-520.
14.
VanderLaan PA, Marqusee E, Krane JF: Usefulness of diagnostic qualifiers for thyroid fine-needle aspirations with atypia of undetermined significance. Am J Clin Pathol 2011;136:572-577.
15.
Renshaw AA: Subclassification of atypical cells of undetermined significance in direct smears of fine-needle aspirations of the thyroid: distinct patterns and associated risk of malignancy. Cancer Cytopathol 2011;119:322-327.
16.
Vivero M, Renshaw AA, Krane JF: Influence of descriptive terminology on management of atypical thyroid fine-needle aspirates. Cancer Cytopathol 2014;122:175-181.
17.
Lee ST, Kim SW, Ki CS, Jang JH, Shin JH, Oh YL, Kim JW, Chung JH: Clinical implication of highly sensitive detection of the BRAF V600E mutation in fine-needle aspirations of thyroid nodules: a comparative analysis of three molecular assays in 4585 consecutive cases in a BRAF V600E mutation-prevalent area. J Clin Endocrinol Metab 2012;97:2299-2306.
18.
Ho AS, Sarti EE, Jain KS, Wang H, Nixon IJ, Shaha AR, Shah JP, Kraus DH, Ghossein R, Fish SA, Wong RJ, Lin O, Morris LG: Malignancy rate in thyroid nodules classified as Bethesda Category III (AUS/FLUS). Thyroid 2014;24:832-839.
19.
Iskandar ME, Bonomo G, Avadhani V, Persky M, Lucido D, Wang B, Marti JL: Evidence for overestimation of the prevalence of malignancy in indeterminate thyroid nodules classified as Bethesda Category III. Surgery 2015;157:510-517.
20.
Gupta S, Ajise O, Dultz L, Wang B, Nonaka D, Ogilvie J, Heller KS, Patel KN: Follicular variant of papillary thyroid cancer: encapsulated, nonencapsulated, and diffuse: distinct biologic and clinical entities. Arch Otolaryngol Head Neck Surg 2012;138:227-233.
21.
Howitt BE, Jia Y, Sholl LM, Barletta JA: Molecular alterations in partially-encapsulated or well-circumscribed follicular variant of papillary thyroid carcinoma. Thyroid 2013;23:1256-1262.
22.
Rivera M, Ricarte-Filho J, Knauf J, Shaha A, Tuttle M, Fagin JA, Ghossein RA: Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs. infiltrative) reveals distinct BRAF and RAS mutation patterns. Mod Pathol 2010;23:1191-1200.
23.
Rivera M, Tuttle RM, Patel S, Shaha A, Shah JP, Ghossein RA: Encapsulated papillary thyroid carcinoma: a clinico-pathologic study of 106 cases with emphasis on its morphologic subtypes (histologic growth pattern). Thyroid 2009;19:119-127.
24.
Vivero M, Kraft S, Barletta JA: Risk stratification of follicular variant of papillary thyroid carcinoma. Thyroid 2013;23:273-279.
25.
Chetty R: Follicular patterned lesions of the thyroid gland: a practical algorithmic approach. J Clin Pathol 2011;64:737-741.
26.
Yang GC, Fried K, Yakoushina TV, Schreiner AM: Encapsulated follicular variant of papillary thyroid carcinoma: fine-needle aspiration with ultrasound and histologic correlation of 41 cases. Acta Cytol 2013;57:26-32.
27.
American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM: Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-1214.
28.
Nishino M, Wang HH: Should the thyroid AUS/FLUS category be further stratified by malignancy risk? Cancer Cytopathol 2014;122:481-483.
29.
Adeniran AJ, Hui P, Chhieng DC, Prasad ML, Schofield K, Theoharis C: BRAF mutation testing of thyroid fine-needle aspiration specimens enhances the predictability of malignancy in thyroid follicular lesions of undetermined significance. Acta Cytol 2011;55:570-575.
© 2015 S. Karger AG, Basel
2015
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.