The predictors of malignancy in thyroid nodules with atypia of undetermined significance or follicular lesions of undetermined significance

Aim: This study aimed to evaluate clinical, radiological and laboratory (neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, and mean platelet value) features that may better define the rate of malignancy in order to contribute to the management of thyroid nodules with AUS/FLUS.Material and Methods: The data of patients with histologic findings of AUS/FLUS on FNA, who underwent surgery at General Surgery Department in a tertiary care hospital between January 2012 and December 2019, were reviewed retrospectively. The patients with any other malign and/or inflammatory diseases and continued on corticosteroid therapy and/or chemotherapy were excluded.Results: The current study included 60 patients (73.3% women), who underwent surgery for 62 thyroid nodules classified as AUS/ FLUS. The specimen pathology revealed a thyroid malignancy in 16 patients, including 10 patients with papillary cancer, 5 patients with micro-papillary thyroid cancer, 1 patient with minimally invasive follicular carcinoma. Ten patients had follicular adenoma. The remaining 35 patients (37 nodules) had nodular colloidal hyperplasia and/or chronic lymphocytic thyroiditis. The rates of malignancy (ROM) and neoplasia (RON) were 25.8% and 40.3%, respectively. Nearly half of the cases (41.9%) had chronic lymphocytic thyroiditis. The malignancy rate in cases with chronic lymphocytic thyroiditis was 26.9%, which was similar in cases without (25%). In multivariate analysis, only microcalcifications were found to be positively associated with malignancy (p: 0.1; [OR] 5.185; CI95% 1.4-19.18).Conclusion: Chronic lymphocytic thyroiditis may lead to overestimation of AUS/FLUS results. It was not associated with malignancy in thyroid nodules with AUS/FLUS. Inflammatory values, such as NLR, PLR and MPV, were not useful markers of malignancy. Among all variables only US findings (microcalcifications according to the current study) may be useful in risk-stratification of malignancyin thyroid nodules with AUS/FLUS.

PDF

___

1. Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid 2017;27:1341-6.
2. 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.
3. Ding J, Jiang L, Fang J, et al. Predictors for malignancy risk in subcentimeter thyroid nodules categorized as Atypia/Follicular Lesion of Undetermined Significance by fine needle aspiration. Sci Rep 2019;9:14973.
4. Haugen BR, Alexander EK, Bible KC, 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.
5. Rago T, Vitti P. Role of thyroid ultrasound in the diagnostic evaluation of thyroid nodules. Best Pract Res Clin Endocrinol Metab 2008;22:913-28.
6. Valderrabano P, McGettigan MJ, Lam C, et al. Thyroid nodules with indeterminate cytology: Utility of the American Thyroid Association sonographic patterns for cancer risk stratification. Thyroid 2018;28:1004-12.
7. Méndez W, Rodgers SE, Lew JI, et al. Role of surgeon performed ultrasound in predicting malignancy in patients with indeterminate thyroid nodules. Ann Surg Oncol 2008;15:2487-92.
8. 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;156:967-70.
9. Yoon JH, Kwon HJ, Kim EK, et al. Subcategorization of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS): a study applying Thyroid Imaging Reporting and Data System (TIRADS). Clin Endocrinol (Oxf) 2016;85:275-82.
10. Gao L, Ma B, Zhou L, et al. The impact of presence of Hashimoto's thyroiditis on diagnostic accuracy of ultrasound-guided fine-needle aspiration biopsy in subcentimeter thyroid nodules: A retrospective study from FUSCC. Cancer Med 2017;6:1014-22.
11. Mulder MB, Khazeni KC, Sussman MS, et al. Chronic lymphocytic thyroiditis may lower accuracy of AUS/ FLUS Cytopathology in surgical patients. J Surg Res 2020;245:244-8.
12. Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol 2010;6:149-63.
13. Seretis C, Gourgiotis S, Gemenetzis G, et al. The significance of neutrophil/lymphocyte ratio as a possible marker of underlying papillary microcarcinomas in thyroidal goiters: a pilot study. Am J Surg 2013;205:691-6.
14. Ari A, Gunver F. Comparison of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with thyroiditis and papillary tumors. J Int Med Res 2019;47:2077-83.
15. Ho AS, Sarti EE, Jain KS, et al. Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS). Thyroid 2014;24:832-9.
16. 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;135:770-5.
17. Kuru B, Atmaca A, Kefeli M. Malignancy rate associated with Bethesda category III (AUS/FLUS) with and without repeat fine needle aspiration biopsy. Diagn Cytopathol 2016;44:394-8.
18. Sullivan PS, Hirschowitz SL, Fung PC, et al. 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;122:866-72.
19. Ohori NP, Nikiforova MN, Schoedel KE, et al. Contribution of molecular testing to thyroid fineneedle aspiration cytology of ‘Follicular Lesion of Undetermined Significance/Atypia of Undetermined Significance’. Cancer Cytopathol 2010;118:17-23.
20. Wu HH, Rose C, Elsheik TM. The Bethesda System for Reporting Thyroid Cytopathology: an experience of 1382 cases in a community practice setting with the implication for risk of neoplasm and risk of malignancy. Diagn Cytopathol 2012;40:399-403.
21. Theoharis CG, Schofield KM, Hammers L, et al. The Bethesda thyroid fine-needle aspiration classification system: year 1 at an academic institution. Thyroid 2009;19:1215-23.
22. Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 2014;106:124.
23. Kutluturk F, Gul SS, Sahin S, et al. Comparison of mean platelet volume, platelet count, neutrophil/ lymphocyte ratio and platelet/lymphocyte ratio in the euthyroid, overt hypothyroid and subclinical hyperthyroid phases of papillary thyroid carcinoma. Endocr Metab Immune Disord Drug Targets 2019;19:859-65.
24. Ozmen S, Timur O, Calik I, et al. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) may be superior to C-reactive protein (CRP) for predicting the occurrence of differentiated thyroid cancer. Endocr Regul 2017;51:131-6.
25. Lee JH, Han K, Kim EK, et al. Risk stratification of thyroid nodules with atypia of undetermined significance/ follicular lesion of undetermined significance (AUS/ FLUS) cytology using ultrasonography patterns defined by the 2015 ATA Guidelines. Ann Otol Rhinol Laryngol 2017;126:625-33.
26. Ha SM, Na DG, Kim JH, et al. Validation of web-based thyroid imaging reporting and data system in atypia or follicular lesion of undetermined significance thyroid nodules. Head Neck 2019;41:2215-24.
27. Choi YJ, Baek JH, Ha EJ, et al. Differences in risk of malignancy and management recommendations in subcategories of thyroid nodules with atypia of undetermined significance or follicular lesion of undetermined significance: the role of ultrasoundguided core-needle biopsy. Thyroid 2014;24:494-501.