Malignancy in Thyroid Nodules with Bethesda III Category on Repeat Fine Needle Aspiration Biopsy
Keywords:
Bethesda III, AUS/FLUS, MalignancyAbstract
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.
;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.
;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):
–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):
–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.
;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.
;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.
;39(8):1699–710. https://pubmed.ncbi.nlm.nih.gov/28493558. https://doi.org/10.1002/hed.24768.
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