OP48 – Selection of Atypia/Follicular Lesion of Unknown Significance Patients for Surgery versus Active Surveillance, without Using Genetic Testing: a Single Institute Experience, Prospective Analysis and Recommendations

      Cohen, Oded 1,2; Tzelnick, Sharon1 ; Lahav, Yonatan1,2 ; Schindel, Doron1,2; Halperin, Doron1,2; Yehuda, Moshe1,2,3,4 1 Department of Otolaryngology Head and Neck Surgery, Kaplan Medical Center, Rehovot, Israel 2 Hadassah School of Medicine, Hebrew University in Jerusalem, Rehovot, Israel 3 Department of Otolaryngology Head and Neck Surgery and Maxillofacial Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel 4 Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel   Background: The recommended management of Atypia/follicular lesion of unknown significance (AUS/FLUS) includes active surveillance (AS), repeated fine needle aspiration (RFNA), diagnostic surgery or genetic testing Purpose: To assess the management of AUS/FLUS patients in without implementing genetic testing. Methods: A single institute cohort study of all adult patients who underwent ultrasound-guided FNA (USGFNA) between January 2009 and January 2013 and were followed until January 2016. Results: The median follow-up time was 4.6 years (range 3.2-6.8). Forty-eight patients (57%) were referred to AS, and 36 patients (43%) were referred for diagnostic surgery. Thirty-six of the AS group (75%) underwent RFNA. An additional eight patients from the AS group subsequently underwent diagnostic surgery. Malignancies rate in the diagnostic surgical samples was 34% (15/44). 61.1% of RFNAs resulted in benign cytology. Analysis of adherence to follow-up in the 36 AS patients showed an adherence rate of only 53%. Men demonstrated better compliance (31.6% vs. 5.8%, respectively, p=0.052), especially males in their 6th decade of life. Discussion: Quality patient selection for surgery based on clinical, sonographic and cytological considerations is feasible, reaching malignancy rate of 34%. RFNA was shown to be a reliable and important tool in the management of these patients, yet active surveillance should be offered after careful assessment of the patient and the nodule’s characteristics Conclusion: When Genetic tests these tests are not feasible, careful management of AUS/FLUS patients may still offer good results. Compliance to follow-up schedules should be a major consideration when selecting patients for AS.   References:
    1. Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2009 Nov;19(11):1159-65
    2. Haugen BR, Alexander EK, Bible KC, Doherty G, Mandel SJ, Nikiforov YE, Pacini F, Randolph G, Sawka A, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward D, Tuttle RM Md, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2015 Oct 14
    3. Crowe A, Linder A, Hameed O, Salih C, Roberson J, Gidley J, Eltoum IA. The impact of implementation of the Bethesda System for Reporting Thyroid Cytopathology on the quality of reporting, “risk” of malignancy, surgical rate, and rate of frozen sections requested for thyroid lesions. Cancer Cytopathol. 2011 Oct 25;119(5):315-21.
    4. Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW.  The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol 2012. 56:333-339
    5. Kwak JY, Han KH, Yoon JH, Moon HJ, Son EJ, Park SH, Jung HK, Choi JS, Kim BM, Kim EK. Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology. 2011 Sep;260(3):892-9.
    6. 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 Oct;38(10):731-9
    7. 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
    8. 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. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012 Aug 23;367(8):705-15.
    9. Labourier E, Shifrin A, Busseniers AE, Lupo MA, Manganelli ML, Andruss B, Wylie D, Beaudenon-Huibregtse S. Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules With Indeterminate Cytology. J Clin Endocrinol Metab. 2015 Jul;100(7):2743-50.
    10. Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, Gooding WE, LeBeau SO, Ohori NP, Seethala RR, Tublin ME, Yip L, Nikiforova MN. Impact of the Multi-Gene ThyroSeq Next-Generation Sequencing Assay on Cancer Diagnosis in Thyroid Nodules with Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Cytology. Thyroid. 2015 Nov;25(11):1217-23.
    11. Wu JX, Lam R, Levin M, Rao J, Sullivan PS, Yeh MW. Effect of malignancy rates on cost-effectiveness of routine gene expression classifier testing for indeterminate thyroid nodules. Surgery. 2016 Jan;159(1):118-29.
    12. Zhang M, Lin O.  Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens. Arch Pathol Lab Med. 2016 Dec;140(12):1338-1344
    13. Lithwick-Yanai G, Dromi N, Shtabsky A, Morgenstern S, Strenov Y3, Feinmesser M, Kravtsov V, Leon ME, Hajdúch M, Ali SZ, VandenBussche CJ, Zhang X, Leider-Trejo L, Zubkov A, Vorobyov S, Kushnir M, Goren Y, Tabak S, Kadosh E, Benjamin H, Schnitzer-Perlman T, Marmor H, Motin M, Lebanony D, Kredo-Russo S, Mitchell H, Noller M, Smith A, Dattner O, Ashkenazi K, Sanden M, Berlin KA, Bar D, Meiri E. Multicentre validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules utilising fine needle aspirate smears.J Clin Pathol. 2016 Oct 26. [Epub ahead of print]
    14. Baloch ZW, LiVolsi VA, Asa SL, Rosai J, Merino MJ, Randolph G, Vielh P, DeMay RM, Sidawy MK, Frable WJ. 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 Jun;36(6):425-37
    15. Yehuda M, Payne RJ, Seaberg RM, MacMillan C, Freeman JL. Fine-needle aspiration biopsy of the thyroid: atypical cytopathological features. Arch Otolaryngol Head Neck Surg. 2007 May;133(5):477-80.
    16. Mathur A, Najafian A, Schneider EB, Zeiger MA, Olson MT. Malignancy risk and reproducibility associated with atypia of undetermined significance on thyroid cytology. Surgery. 2014 Dec;156(6):1471-6; discussion1476.
    17. Wu HH, Inman A, Cramer HM. Subclassification of “atypia of undetermined significance” in thyroid fine-needle aspirates.Diagn Cytopathol. 2014 Jan;42(1):23-9.
    18. 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 Oct 25;119(5):322-7.
    19. 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 Nov; 19(11): 1167-214
    20. Bongiovanni M, Crippa S, Baloch Z, Piana S, Spitale A, Pagni F, Mazzucchelli L, Di BC, Faquin W. Comparison of 5-tiered and 6-tiered diagnostic systems for the reporting of thyroid cytopathology: a multi-institutional study. Cancer Cytopathol. 2012 120:117-125
    21. Ohori NP, Schoedel KE. Variability in the atypia of undetermined significance/follicular lesion of undetermined significance diagnosis in the Bethesda System for Reporting Thyroid Cytopathology: sources and recommendations. Acta Cytol. 2011 55:492-498
    22. 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.
    23. Yang J, Schnadig V, Logrono R, et al. Fine-needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations. Cancer. 2007;111:306-315.
    24. 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 May;24(5):832-9
    25. Oertel YC, Miyahara-Felipe L, Mendoza MG, Yu K. Value of repeated fine needle aspirations of the thyroid: an analysis of over ten thousand FNAs. Thyroid. 2007 Nov;17(11):1061-6..
    26. Nou E, Kwong N, Alexander LK, Cibas ES, Marqusee E, Alexander EK Determination of the optimal time interval for repeat evaluation after a benign thyroid nodule aspiration. J Clin Endocrinol Metab 201499:510-516
    27. Chen JC, Pace SC, Chen BA, Khiyami A, McHenry CR. Yield of repeat fine-needle aspiration biopsy and rate of malignancy in patients with atypia or follicular lesion of undetermined significance: the impact of the Bethesda System for Reporting Thyroid Cytopathology. Surgery. 2012 Dec;152(6):1037-44
    28. Dincer N, Balci S, Yazgan A, Guney G, Ersoy R, Cakir B, Guler G. Follow-up of atypia and follicular lesions of undetermined significance in thyroid fine needle aspiration cytology. Cytopathology. 2013 Dec;24(6):385-90.
    29. Hirsch D, Robenshtok E, Bachar G, Braslavsky D, Benbassat C. The Implementation of the Bethesda System for Reporting Thyroid Cytopathology Improves Malignancy Detection Despite Lower Rate of Thyroidectomy in Indeterminate Nodules. World J Surg. 2015 Aug;39(8):1959-65. doi: 10.1007/s00268-015-3032-6.
    30. Khoncarly SM, Tamarkin SW, McHenry CR. Can ultrasound be used to predict malignancy in patients with a thyroid nodule and an indeterminate fine-needle aspiration biopsy? Surgery. 2014 Oct;156(4):967-70
    31. Russ G, Leboulleux S, Leenhardt L, Hegedüs L. Thyroid incidentalomas: epidemiology, risk stratification with ultrasound and workup. Eur Thyroid J. 2014 Sep;3(3):154-63.
    32. Choi SH1, Kim EK, Kwak JY, Kim MJ, Son EJ. Interobserver and intraobserver variations in ultrasound assessment of thyroid nodules. Thyroid. 2010 Feb;20(2):167-72.
    33. Cibas ES, Baloch ZW, Fellegara G, LiVolsi VA, Raab SS, Rosai J, Diggans J, Friedman L, Kennedy GC, Kloos RT, Lanman RB, Mandel SJ, Sindy N, Steward DL, Zeiger MA, Haugen BR, Alexander EK. A prospective assessment defining the limitations of thyroid nodule pathologic evaluation. Ann Intern Med. 2013 Sep 3;159(5):325-32.
    34. Brauner E, Holmes BJ, Krane JF, Nishino M4, 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 Jul;25(7):789-96


Leave a Reply