Malignancy in Thyroid Nodules with Bethesda III Category on Repeat Fine Needle Aspiration Biopsy

Jennifer Lourdes Ng; Luz Margaret Escueta; Oliver Allan Dampil

doi:10.15605/jafes.038.02.19

Authors

Jennifer Lourdes Ng St. Luke's Medical Center, Quezon City https://orcid.org/0000-0002-1615-9900
Luz Margaret Escueta St. Luke's Medical Center, Quezon City
Oliver Allan Dampil St. Luke's Medical Center, Quezon City

DOI:

https://doi.org/10.15605/jafes.038.02.19

Keywords:

Bethesda III, AUS/FLUS, Malignancy

Abstract

Objectives. This study aimed to evaluate the risk of malignancy for nodules repeatedly classified as Bethesda category III on fine needle aspiration biopsy (FNAB).

Methodology. A chart review on a series of 59 patients seen with thyroid nodules who underwent both initial and repeat
FNAB at the Diabetes, Thyroid and Endocrine Center of St. Luke’s Medical Center, Quezon City was conducted. The Thyroid Registry was utilized to collect each patient’s demographic and clinical characteristics, ultrasonographic features of thyroid nodules along with the cytopathologic and histopathologic results. The subclassification of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) were retrieved from the cytopathology reports using the institution’s electronic Healthcare-Results Management System.

Results. A total of 59 adult patients with thyroid nodules were included. Nodules which were initially AUS/FLUS turned out to be malignant on repeat FNAB in 38 patients with a prevalence of 64.41% (95% CI: 50.87-76.45%). There was no significant difference with regards to clinical, ultrasonographic and cytopathologic features of malignancy between benign and malignant nodules.

Conclusion. Findings of this study support surgical intervention as a reasonable option after a repeat Bethesda III classification on FNAB. However, the small sample size warrants confirmation in future studies with a representative sample of patients.

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References

Bayona A, Benavent P, Muriel A, et al. Outcomes of repeat fine needle aspiration biopsy for AUS/FLUS thyroid nodules. Eur J Endocrinol. 2021;185(4):497-506. https://pubmed.ncbi.nlm.nih.gov/34313606. https://doi.org/10.1530/EJE-21-0330.

Na DG, Kim JH, Sung JY, et al. Core-needle biopsy is more useful than repeat fine-needle aspiration in thyroid nodules read as nondiagnostic or atypia of undetermined significance by the Bethesda system for

reporting thyroid cytopathology. Thyroid. 2012;22(5):468-75. https://pubmed.ncbi.nlm.nih.gov/22304417. https://doi.org/10.1089/thy.2011.0185.

Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Thyroid. 2009;19(11):1159-65. https://pubmed.ncbi.nlm.nih.gov/19888858. https://doi.org/10.1089/thy.2009.0274.

American Thyroid Association Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer; 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(11):1167–114. https://pubmed.ncbi.nlm.nih.gov/19860577. https://doi.org/10.1089/thy.2009.0110.

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: Executive summary of recommendations. endocrine practice. 2010;16(3):468–75. https://pubmed.ncbi.nlm.nih.gov/20551008. https://doi.org/10.4158/EP.16.3.468.

Ho AS, Sarti EE, Jain KS, et al. Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS). Thyroid. 2014;24(5):832–9. https://pubmed.ncbi.nlm.nih.gov/24341462. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948206. https://doi.org/10.1089/thy.2013.0317.

Gweon HM, Son EJ, Youk JH, Kim JA. Thyroid nodules with Bethesda system III cytology: Can ultrasonography guide the next step? Ann Surg Oncol. 2013;20(9):3083–8. https://pubmed.ncbi.nlm.nih.gov/23700214. https://doi.org/10.1245/s10434-013-2990-x.

Yoo WS, Choi HS, Cho SW, et al. The role of ultrasound findings in the management of thyroid nodules with atypia or follicular lesions of undetermined significance. Clin Endocrinol (Oxf). 2014;80(5):735–42. https://pubmed.ncbi.nlm.nih.gov/24117478. https://doi.org/10.1111/cen.12348.

Mehta RS, Carty SE, Ohori NP, et al. Nodule size is an independent predictor of malignancy in mutation-negative nodules with follicular

lesion of undetermined significance cytology. Surgery. 2013;154(4):730–6. https://pubmed.ncbi.nlm.nih.gov/24074409. https://doi.org/10.1016/j.surg.2013.05.015

Carr R, Ustun B, Chhieng D, et al. Radiologic and clinical predictors of malignancy in the follicular lesion of undetermined significance of the thyroid. Endocr Pathol. 2013;24(2):62–8. https://pubmed.ncbi.nlm.nih.gov/23595630. https://doi.org/10.1007/s12022-013-9240-4.

Rosario PW. Thyroid nodules with atypia or follicular lesions of undetermined significance (Bethesda Category III): Importance of ultrasonography and cytological subcategory. Thyroid. 2014;24(7):1115–20. https://pubmed.ncbi.nlm.nih.gov/24684285. https://doi.org/10.1089/thy.2013.0650.

Ogmen BE, Aydin B, Kilinc I, Altinboga, AA, Ersoy R, Cakir B. Can repeat biopsies change the prognoses of AUS/FLUS nodule? Eur

Thyroid. 2020;9(2):92-8. https://pubmed.ncbi.nlm.nih.gov/32257958. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109390. https://doi.org/10.1159/000504705.

Broome JT, Cate F, Solorzano CC. Utilization and impact of repeat biopsy for follicular lesion/atypia of undetermined significance. World J Surg. 2014;38(3): 628–33. https://pubmed.ncbi.nlm.nih.gov/24233659. https://doi.org/10.1007/s00268-013-2330-0.

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(5):770–5. https://pubmed.ncbi.nlm.nih.gov/21502433. https://doi.org/10.1309/AJCP4P2GCCDNHFMY.

Hong SH, Lee H, Cho MS, Lee JE, Sung YA, Hong YS. Malignancy risk and related factors of atypia of undetermined significance/follicular lesion of undetermined significance in thyroid fine needle aspiration.

Int J Endocrinol. 2018;2018:4521984. https://pubmed.ncbi.nlm.nih.gov/30154840. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091291. https://doi.org/10.1155/2018/4521984.

Wong LQ, LiVolsi VA, Baloch ZW. Diagnosis of atypia/follicular lesion of undetermined significance: An institutional experience. Cytojournal. 2014;11(1):23. https://pubmed.ncbi.nlm.nih.gov/25210530. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158655. https://doi.org/10.4103/1742-6413.139725.

Kim DS, Kim DW, Heo YJ, et al. Utility of including BRAF mutation analysis with ultrasonographic and cytological diagnoses in ultrasonography-guided fine-needle aspiration of thyroid nodules. PLoS ONE. 2018;13(8):e0202687. https://pubmed.ncbi.nlm.nih.gov/30118506. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097667. https://doi.org/10.1371/journal.pone.0202687.

Burch HB, Burman KD, Cooper DS, Hennessey JV, Vietor NO. A 2015 Survey of clinical practice patterns in the management of thyroid nodules. J Clin Endocrinol Metab. 2016;101(7):2853-62. https://pubmed.ncbi.nlm.nih.gov/27014951.

https://doi.org/10.1210/jc.2016-1155.

Stewardson P, Eszlinger M, Paschke R. Diagnosis of endocrine disease: Usefulness of genetic testing of fine-needle aspirations for diagnosis of thyroid cancer. Eur J Endocrinol. 2022;187(3):R41-52. https://pubmed.ncbi.nlm.nih.gov/35900312. https://doi.org/10.1530/EJE-21-1293.

Nicholson KJ, Roberts MS, McCoy KL, Carty SE, Yip L. Molecular testing versus diagnostic lobectomy in Bethesda III/IV thyroid nodules: A cost-effectiveness analysis. Thyroid. 2019;29(9):1237-43. https://pubmed.ncbi.nlm.nih.gov/31407625. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366255. https://doi.org/10.1089/thy.2018.0779.

Elomami A, Elhag SA, Alseddeeqi E. Cytological sub-classification of atypia of undetermined significance may predict malignancy risk in thyroid nodules. Acta Cytol. 2012;65(3):205-12. https://pubmed.ncbi.nlm.nih.gov/33524971.

https://doi.org/10.1159/000513066.

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;152(6):1037-44. https://pubmed.ncbi.nlm.nih.gov/23040711. https://doi.org/10.1016/j.surg.2012.08.052.

Abelardo AD, Sotalbo K. Clinical management of thyroid aspirates diagnosed as atypia of undetermined significance in the

Philippines. Gland Surg. 2020;9(5):1788-96. https://pubmed.ncbi.nlm.nih.gov/33224855. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667114. https://doi.org/10.21037/gs-20-426

Yoo MR, Gweon HM, Park AY, et al. Repeat diagnoses of Bethesda Category III thyroid nodules: What to do next? PLoS One. 2015;10(6):e0130138. https://pubmed.ncbi.nlm.nih.gov/26115096. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482684. https://doi.org/10.1371/journal.pone.0130138.

Kocjan G, Chandra A, Cross PA, et al. The interobserver reproducibility of thyroid fine-needle aspiration using the UK Royal College of Pathologists’ classification system. Am J Clin Pathol. 2011;135(6):852-9. https://pubmed.ncbi.nlm.nih.gov/21571958. https://doi.org/10.1309/AJCPZ33MVMGZKEWU.

Park JH, Kim HK, Kang SW, et al. Second opinion in thyroid fine-needle aspiration biopsy by the Bethesda system. Endocr J. 2012;59(3):205-12. https://pubmed.ncbi.nlm.nih.gov/22156326. https://doi.org/10.1507/endocrj.ej11-0274.

Mileva M, Stoilovska B, Jovanovska A, et al. Thyroid cancer detection rate and associated risk factors in patients with thyroid nodules classified as Bethesda category III. Radiol Oncol. 2018;52(4):370–6.

https://pubmed.ncbi.nlm.nih.gov/30265655. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287180. https://doi.org/10.2478/raon-2018-0039.

Cibas ES, Ali SZ. The 2017 Bethesda System for reporting thyroid cytopathology. Thyroid. 2017;27(11):1341-6. Phttps://pubmed.ncbi.nlm.nih.gov/29091573. https://doi.org/10.1089/thy.2017.0500.

Gan TR, Nga ME, Lum JH, 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(4):245–56. https://pubmed.ncbi.nlm.nih.gov/28192631. https://doi.org/10.1002/cncy.21823.

Ahn SH, Kim SD, Jeong WJ. Comparison of risk of malignancy in a subgroup with atypia of undetermined significance/follicular lesion of undetermined significance: A meta-analysis. Head Neck. 2017;39(8):1699–710. https://pubmed.ncbi.nlm.nih.gov/28493558. https://doi.org/10.1002/hed.24768.