Korean Journal of Radiology

The Korean Society of Radiology (대한영상의학회)
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Risk Stratification of Thyroid Nodules Diagnosed as Bethesda Category III by Ultrasound, Size, and Cytology

  • Hye Shin Ahn (Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Dong Gyu Na (Department of Radiology, Gangneung Asan Hospital, University of Ulsan College of Medicine) ;
  • Ji-Hoon Kim (Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine)
  • Received : 2024.03.25
  • Accepted : 2024.08.03
  • Published : 2024.10.01
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Abstract

Objective: This study aimed to evaluate the performance of an integrated risk stratification system (RSS) based on ultrasound (US) RSSs, nodule size, and cytology subcategory for diagnosing malignancy in thyroid nodules initially identified as Bethesda category III on fine-needle aspiration. Materials and Methods: This retrospective study was conducted at two institutions and included consecutive patients with Bethesda category III nodules, and final diagnoses confirmed by repeat biopsy or surgery. A total of 320 Bethesda category III nodules (≥1 cm) from 309 patients (223 female and 86 male; mean age, 50.9 ± 12.0 years) were included. The malignancy risk of Bethesda category III nodules and predictors of malignancy were assessed according to US RSSs, nodule size, and cytology subcategory. The diagnostic performances of US-size cytology (USC) RSS and US RSS alone for malignancy were compared. Results: The intermediate or high suspicion US category independently increased the malignancy risk in all US RSSs (P ≤ 0.001). Large nodule size (≥3 cm) independently increased the malignancy risk of low- or intermediate suspicion US category nodules. Additionally, the atypia of undetermined significance cytology subcategory independently increased the malignancy risk of low suspicion US category nodules in most US RSSs. The area under the receiver operating characteristic curve of the USC RSSs was greater than that of the US RSSs alone (P < 0.048). Malignancy was not found in the very low risk category of USC RSS. Conclusion: The diagnostic performance of USC RSS for malignancy was superior to that of US RSS alone in Bethesda category III nodules. Malignancy can be ruled out in the very low-risk category of USC RSS.

Keywords

References

  1. 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
  2. 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
  3. Ohori NP, Nikiforova MN, Schoedel KE, LeBeau SO, Hodak SP, Seethala RR, 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
  4. Renshaw AA. Should "atypical follicular cells" in thyroid fine-needle aspirates be subclassified? Cancer Cytopathol 2010;118:186-189
  5. 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
  6. Rabaglia JL, Kabbani W, Wallace L, Holt S, Watumull L, Pruitt J, et al. 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 1272-1273
  7. Vanderlaan PA, Krane JF, Cibas ES. The frequency of 'atypia of undetermined significance' interpretations for thyroid fine-needle aspirations is negatively correlated with histologically proven malignant outcomes. Acta Cytol 2011;55:512-517
  8. Sullivan PS, Hirschowitz SL, Fung PC, Apple SK. The impact of atypia/follicular lesion of undetermined significance and repeat fine-needle aspiration: 5 years before and after implementation of the Bethesda system. Cancer Cytopathol 2014;122:866-872
  9. Allen L, Al Afif A, Rigby MH, Bullock MJ, Trites J, Taylor SM, et al. The role of repeat fine needle aspiration in managing indeterminate thyroid nodules. J Otolaryngol Head Neck Surg 2019;48:16
  10. Evranos Ogmen B, Aydin C, Kilinc I, Aksoy Altinboga A, Ersoy R, Cakir B. Can repeat biopsies change the prognoses of AUS/FLUS nodule? Eur Thyroid J 2020;9:92-98
  11. Ali SZ, Baloch ZW, Cochand-Priollet B, Schmitt FC, Vielh P, VanderLaan PA. The 2023 Bethesda system for reporting thyroid cytopathology. Thyroid 2023;33:1039-1044
  12. Kholova I, Ludvikova M. Thyroid atypia of undetermined significance or follicular lesion of undetermined significance: an indispensable Bethesda 2010 diagnostic category or waste garbage? Acta Cytol 2014;58:319-329
  13. Straccia P, Rossi ED, Bizzarro T, Brunelli C, Cianfrini F, Damiani D, et al. A meta-analytic review of the Bethesda system for reporting thyroid cytopathology: has the rate of malignancy in indeterminate lesions been underestimated? Cancer Cytopathol 2015;123:713-722
  14. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1-133
  15. Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedus L, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules--2016 update. Endocr Pract 2016;22:622-639
  16. Ha EJ, Chung SR, Na DG, Ahn HS, Chung J, Lee JY, et al. 2021 Korean thyroid imaging reporting and data system and imaging-based management of thyroid nodules: Korean Society of Thyroid Radiology consensus statement and recommendations. Korean J Radiol 2021;22:2094-2123
  17. Haddad RI, Bischoff L, Ball D, Bernet V, Blomain E, Busaidy NL, et al. Thyroid carcinoma, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2022;20:925-951
  18. Durante C, Hegedus L, Czarniecka A, Paschke R, Russ G, Schmitt F, et al. 2023 European Thyroid Association clinical practice guidelines for thyroid nodule management. Eur Thyroid J 2023;12:e230067
  19. Borson-Chazot F, Buffet C, Decaussin-Petrucci M, Cao CD, Drui D, Leboulleux S, et al. SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: synthesis and algorithms. Ann Endocrinol (Paris) 2022;83:440-453
  20. Hong MJ, Na DG, Baek JH, Sung JY, Kim JH. Cytology-ultrasonography risk-stratification scoring system based on fine-needle aspiration cytology and the Korean-thyroid imaging reporting and data system. Thyroid 2017;27:953-959
  21. Valderrabano P, McGettigan MJ, Lam CA, Khazai L, Thompson ZJ, Chung CH, et al. Thyroid nodules with indeterminate cytology: utility of the American Thyroid Association sonographic patterns for cancer risk stratification. Thyroid 2018;28:1004-1012
  22. Dickey MV, Nguyen A, Wiseman SM. Cancer risk estimation using American College of Radiology thyroid imaging reporting and data system for cytologically indeterminate thyroid nodules. Am J Surg 2022;224:653-656
  23. Staibano P, Forner D, Noel CW, Zhang H, Gupta M, Monteiro E, et al. Ultrasonography and fine-needle aspiration in indeterminate thyroid nodules: a systematic review of diagnostic test accuracy. Laryngoscope 2022;132:242-251
  24. Rosario PW, Calsolari MR. Importance of cytological subclassification of thyroid nodules with Bethesda category III cytology (AUS/FLUS) into architectural atypia only and nuclear atypia: a prospective study. Diagn Cytopathol 2017;45:604-607
  25. Gan TR, Nga ME, Lum JH, Wong WM, Tan WB, Parameswaran R, et al. Thyroid cytology-nuclear versus architectural atypia within the "atypia of undetermined significance/follicular lesion of undetermined significance" Bethesda category have significantly different rates of malignancy. Cancer Cytopathol 2017;125:245-256
  26. Eisa N, Khan A, Akhter M, Fensterwald M, Saleem S, Fananapazir G, et al. Both ultrasound features and nuclear atypia are associated with malignancy in thyroid nodules with atypia of undetermined significancence. Ann Surg Oncol 2018;25:3913-3918
  27. Rosario PW. Thyroid nodules with atypia or follicular lesions of undetermined significance (Bethesda category III): importance of ultrasonography and cytological subcategory. Thyroid 2014;24:1115-1120
  28. Mehta RS, Carty SE, Ohori NP, Hodak SP, Coyne C, LeBeau SO, et al. Nodule size is an independent predictor of malignancy in mutation-negative nodules with follicular lesion of undetermined significance cytology. Surgery 2013;154:730-736; discussion 736-738
  29. Cohen JF, Korevaar DA, Altman DG, Bruns DE, Gatsonis CA, Hooft L, et al. STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open 2016;6:e012799
  30. Joo L, Na DG, Kim JH, Seo H. Comparison of core needle biopsy and repeat fine-needle aspiration in avoiding diagnostic surgery for thyroid nodules initially diagnosed as atypia/follicular lesion of undetermined significance. Korean J Radiol 2022;23:280-288
  31. Russ G, Bonnema SJ, Erdogan MF, Durante C, Ngu R, Leenhardt L. European Thyroid Association Guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: the EU-TIRADS. Eur Thyroid J 2017;6:225-237
  32. Tessler FN, Middleton WD, Grant EG, Hoang JK, Berland LL, Teefey SA, et al. ACR thyroid imaging, reporting and data system (TI-RADS): white paper of the ACR TI-RADS committee. J Am Coll Radiol 2017;14:587-595
  33. Kwon D, Kulich M, Mack WJ, Monedero RM, Joyo E, Angell TE. Malignancy risk of thyroid nodules that are not classifiable by the American Thyroid Association ultrasound risk stratification system: a systematic review and meta-analysis. Thyroid 2023;33:593-602
  34. Gwon HY, Na DG, Noh BJ, Paik W, Yoon SJ, Choi SJ, et al. Thyroid nodules with isolated macrocalcifications: malignancy risk of isolated macrocalcifications and postoperative risk stratification of malignant tumors manifesting as isolated macrocalcifications. Korean J Radiol 2020;21:605-613
  35. Moon WJ, Baek JH, Jung SL, Kim DW, Kim EK, Kim JY, et al. Ultrasonography and the ultrasound-based management of thyroid nodules: consensus statement and recommendations. Korean J Radiol 2011;12:1-14
  36. Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Thyroid 2009;19:1159-1165
  37. Na DG, Min HS, Lee H, Won JK, Seo HB, Kim JH. Role of core needle biopsy in the management of atypia/follicular lesion of undetermined significance thyroid nodules: comparison with repeat fine-needle aspiration in subcategory nodules. Eur Thyroid J 2015;4:189-196
  38. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33:159-174
  39. Slowin'ska-Klencka D, Wysocka-Konieczna K, Klencki M, Popowicz B. Diagnostic value of six thyroid imaging reporting and data systems (TIRADS) in cytologically equivocal thyroid nodules. J Clin Med 2020;9:2281
  40. Yoo WS, Ahn HY, Ahn HS, Chung YJ, Kim HS, Cho BY, et al. Malignancy rate of Bethesda category III thyroid nodules according to ultrasound risk stratification system and cytological subtype. Medicine (Baltimore) 2020;99:e18780
  41. Larcher de Almeida AM, Delfim RLC, Vidal APA, Chaves MCDCM, Santiago ACL, Gianotti MF, et al. Combining the American Thyroid Association's ultrasound classification with cytological subcategorization improves the assessment of malignancy risk in indeterminate thyroid nodules. Thyroid 2021;31:922-932
  42. Hong MJ, Na DG, Baek JH, Sung JY, Kim JH. Impact of nodule size on malignancy risk differs according to the ultrasonography pattern of thyroid nodules. Korean J Radiol 2018;19:534-541
  43. Machens A, Holzhausen HJ, Dralle H. The prognostic value of primary tumor size in papillary and follicular thyroid carcinoma. Cancer 2005;103:2269-2273
  44. Nguyen XV, Roy Choudhury K, Tessler FN, Hoang JK. Effect of tumor size on risk of metastatic disease and survival for thyroid cancer: implications for biopsy guidelines. Thyroid 2018;28:295-300
  45. Kim GR, Yoon JH, Kim EK, Moon HJ, Kwak JY. Benign aspirates on follow-up FNA may be enough in patients with initial Atypia of undetermined significance/follicular lesion of undetermined significance. Int J Endocrinol 2014;2014:354612