The possibilities of ultrasound imaging in the diagnosis of follicular neoplasia of the thyroid gland

Thyroid cancer is the most common cancer of the endocrine system. The diagnosis of thyroid cancer has taken a step forward due to the introduction of fine-needle biopsy of the thyroid gland with subsequent evaluation of cytological material using the Bethesda system. One category of this classification traditionally remains a gray area of diagnosis. The detection of a follicular tumor in the cytological material (category IV according to Bethesda) does not allow one to reliably classify the neoplasia as benign or malignant and requires surgical intervention. The traditional informative and widely used method for diagnosing thyroid tumors is ultrasound. However, the sensitivity and specificity of the method varies over a wide range. This review analyzes the literature on the possibilities of ultrasound diagnostics in assessing the malignant potential of follicular tumors of the thyroid gland.

1. Поляков А.П., Мордовский А.В., Никифорович П.А. и др. Клинические наблюдения эффективности терапии метастатического радиойодрефрактерного высокодифференцированного рака щитовидной железы мультикиназными ингибиторами. Эндокринная хирургия 2018;12(2):81–8. DOI: 10.14341/serg9614 Polyakov A.P., Mordovsky A.V., Nikiforovich P.A. et al. Clinical observations of the effectiveness of therapy of metastatic radioiodrefract highly differentiated thyroid cancer with multikinase inhibitors. Ehndokrinnaya khirurgiya = Endocrine Surgery 2018;12(2):81–8. DOI: 10.14341/serg961

2. Sung H., Ferlay J., Siegel R.L. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clini 2021;71(3):209–49. DOI: 10.3322/caac.21660

3. De Crea C., Raffaelli M., Sessa L. et al. Actual incidence and clinical behaviour of follicular thyroid carcinoma: an institutional experience. Scientific World Journal 2014;2014:952095. DOI: 10.1155/2014/952095

4. WHO classification of tumours of endocrine organs. 4th edn. Ed. by R.V. Lloyd, R.Y. Osamura, G. Kloppel, J. Rosai. 2017. Available at: https://publications.iarc.fr/Book-And-Report-Series/ Who-Classification-Of-Tumours/WHO-Classification-OfTumours-Of-Endocrine-Organs-2017.

5. Cibas E.S., Ali S.Z. The 2017 Bethesda System for reporting thyroid cytopathology. Thyroid 2017;27(11):1341–6. DOI: 10.1089/ thy.2017.0500

6. McHenry C.R., Phitayakorn R. Follicular adenoma and carcinoma of the thyroid gland. Oncologist 2011;16(5):585–93. DOI: 10.1634/ theoncologist.2010-0405

7. Lamartina L., Grani G., Durante C., Filetti S. Recent advances in managing differentiated thyroid cancer. F1000Res 2018;7:86. DOI: 10.12688/f1000research.12811.1

8. Dolidze D.D., Shabunin A.V., Mumladze R.B. et al. A narrative review of preventive central lymph node dissection in patients with papillary thyroid cancer – a necessity or an excess. Front Oncol 2022;12:906695. DOI: 10.3389/fonc.2022.906695

9. Li W., Song Q., Lan Y. et al. The value of sonography in distinguishing follicular thyroid carcinoma from adenoma. Cancer Manag Res 2021;13:3991–4002. DOI: 10.2147/CMAR.S307166

10. Zhang J., Zhang X., Meng Y., Chen Y. Contrast-enhanced ultrasound for the differential diagnosis of thyroid nodules: An updated meta-analysis with comprehensive heterogeneity analysis. PLoS One 2020;15(4):e0231775. DOI: 10.1371/journal.pone.0231775

11. Haugen B.R., Alexander E.K., Bible K.C. 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): 1–133. DOI: 10.1089/thy.2015.0020

12. Koike E., Noguchi S., Yamashita H. et al. Ultrasonographic characteristics of thyroid nodules: prediction of malignancy. Arch Surg 2001;136(3):334–7. DOI: 10.1001/archsurg.136.3.334

13. Rago T., Di Coscio G., Basolo F. et al. Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: results from a series of 505 consecutive patients. Clin Endocrinol (Oxf) 2007;66(1):13–20. DOI: 10.1111/j.1365-2265.2006.02677.x

14. Solymosi T., Hegedüs L., Bodor M., Nagy E.V. EU-TIRADS-based omission of fine-needle aspiration and cytology from thyroid nodules overlooks a substantial number of follicular thyroid cancers. Int J Endocrinol 2021:9924041. DOI: 10.1155/2021/9924041

15. Lin Y., Lai S., Wang P. et al. Performance of current ultrasoundbased malignancy risk stratification systems for thyroid nodules in patients with follicular neoplasms. Eur Radiol 2022;32(6):3617–30. DOI: 10.1007/s00330-021-08450-3

16. Shin J.H., Baek J.H., Chung J. et al. Ultrasonography diagnosis and imaging-based management of thyroid nodules: revised Korean Society of Thyroid Radiology Consensus Statement and Recommendations. Korean Journal Radiol 2016;17(3):370–95. DOI: 10.3348/kjr.2016.17.3.370

17. Tessler F.N., Middleton W.D., Grant E.G. et al. ACR Thyroid Imaging, Reporting and Data System (TI-RADS): White Paper of the ACR TI-RADS Committee. J Am College Radiol 2017;14(5):587–95. DOI: 10.1016/j.jacr.2017.01.046

18. Zhou J., Yin L., Wei X. et al. Chinese guidelines for ultrasound malignancy risk stratification of thyroid nodules: the C-TIRADS. Endocrine 2020;70(2):256–79. DOI: 10.1007/s12020-020- 02441-y

19. Castellana M., Grani G., Radzina M. et al. Performance of EU-TIRADS in malignancy risk stratification of thyroid nodules: a meta-analysis. Eur J Endocri 2020;183(3):255–64. DOI: 10.1530/ EJE-20-0204

20. Chen Q., Lin M., Wu S. Validating and comparing C-TIRADS, K-TIRADS and ACR-TIRADS in stratifying the malignancy risk of thyroid nodules. Front Endocrinol (Lausanne) 2022;13:899575. DOI: 10.3389/fendo.2022.899575

21. Raber W., Kaserer K., Niederle B., Vierhapper H. Risk factors for malignancy of thyroid nodules initially identified as follicular neoplasia by fine-needle aspiration: results of a prospective study of one hundred twenty patients. Thyroid 2000;10(8):709–12. DOI: 10.1089/10507250050137806

22. Lin J.D., Hsueh C., Chao T.C. et al. Thyroid follicular neoplasms diagnosed by high-resolution ultrasonography with fine needle aspiration cytology. Acta Cytologica 1997;41(3):687–91. DOI: 10.1159/000332685

23. Sillery J.C., Reading C.C., Charboneau J.W. et al. Thyroid follicular carcinoma: sonographic features of 50 cases. Am J Roentgenol 2010;194(1):44–54. DOI: 10.2214/AJR.09.3195

24. Moon W.J., Jung S.L., Lee J.H. et al. Benign and malignant thyroid nodules: US differentiation-multicenter retrospective study. Radiology 2008;247(3):762–70. DOI: 10.1148/radiol.2473070944

25. Kuo T.C., Wu M.H., Chen K.Y. et al. Ultrasonographic features for differentiating follicular thyroid carcinoma and follicular adenoma. Asian J Surg 2020;43(1):339–46. DOI: 10.1016/j.asjsur.2019.04.016

26. Seo H.S., Lee D.H., Park S.H. et al. Thyroid follicular neoplasms: can sonography distinguish between adenomas and carcinomas? J Clin Ultrasound 2009;37(9):493–500. DOI: 10.1002/jcu.20625

27. Weber A.L., Randolph G., Aksoy F.G. The thyroid and parathyroid glands. CT and MR imaging and correlation with pathology and clinical findings. Radiol Clinics North Am 2000;38(5):1105–29. DOI: 10.1016/s0033-8389(05)70224-4

28. Pompili G., Tresoldi S., Primolevo A. et al. Management of thyroid follicular proliferation: an ultrasound-based malignancy score to opt for surgical or conservative treatment. Ultrasound Med Biol 2013;39(8):1350–5. DOI: 10.1016/j.ultrasmedbio.2013.02.464

29. Fukunari N., Nagahama M., Sugino K. et al. Clinical evaluation of color Doppler imaging for the differential diagnosis of thyroid follicular lesions. World J Surg 2004;28(12):1261–5. DOI: 10.1007/ s00268-004-7597-8

30. Frates M.C., Benson C.B., Doubilet P.M. et al. Can color Doppler sonography aid in the prediction of malignancy of thyroid nodules? J Ultrasound Med 2003;22(2):127–31; quiz 32–4. DOI: 10.7863/ jum.2003.22.2.127

31. Welker M.J., Orlov D. Thyroid nodules. Am Fam Physician 2003;67(3):559–66.

32. Sun J., Cai J., Wang X. Real-time ultrasound elastography for differentiation of benign and malignant thyroid nodules: a meta-analysis. J Ultrasound Med 2014;33(3):495–502. DOI: 10.7863/ultra.

33. 3.495 33. Rago T., Santini F., Scutari M. et al. Elastography: new developments in ultrasound for predicting malignancy in thyroid nodules. J Clin Endocrinol Metab 2007;92(8):2917–22. DOI: 10.1210/jc.2007-0641

34. Asteria C., Giovanardi A., Pizzocaro A. et al. US-elastography in the differential diagnosis of benign and malignant thyroid nodules. Thyroid 2008;18(5):523–31. DOI: 10.1089/thy.2007.0323

35. Zhao C.-K., Xu H.-X. Ultrasound elastography of the thyroid: principles and current status. Ultrasonography 2019;38(2):106–24. DOI: 10.14366/usg.18037

36. Dighe M.K. Elastography of Thyroid Masses. Ultrasound Clin 2014;9(1):13–24. DOI: 10.1016/j.cult.2013.08.001

37. Hong Y.-R., Yan C.-X., Mo G.-Q. et al. Conventional US, elastography, and contrast enhanced US features of papillary thyroid microcarcinoma predict central compartment lymph node metastases. Sci Rep 2015;5:7748. DOI: 10.1038/srep07748

38. Xu Y., Qi X., Zhao X. et al. Clinical diagnostic value of contrastenhanced ultrasound and TI-RADS classification for benign and malignant thyroid tumors: one comparative cohort study. Medicine 2019;98(4):e14051. DOI: 10.1097/MD.0000000000014051

39. Wang Y., Dong T., Nie F. et al. Contrast-enhanced ultrasound in the differential diagnosis and risk stratification of ACR TI-RADS category 4 and 5 thyroid nodules with non-hypovascular. Front Oncol 2021;11:662273. DOI: 10.3389/fonc.2021.662273

40. Zhang Y., Luo Y.K., Zhang M.B. et al. Diagnostic accuracy of contrast-enhanced ultrasound enhancement patterns for thyroid nodules. Med Sci Monit 2016;5(22):4755–64. DOI: 10.12659/ MSM.899834

41. Sakorafas G.H., Koureas A., Mpampali I. et al. Patterns of lymph node metastasis in differentiated thyroid cancer; clinical implications with particular emphasis on the emerging role of compartment-oriented lymph node dissection. Oncol Res Treat 2019;42(3):143–7. DOI: 10.1159/000488905

42. Leenhardt L., Erdogan M.F., Hegedus L. et al. 2013 European thyroid association guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer. Eur Thyroid J 2013;2(3):147–59. DOI: 10.1159/000354537

43. Ha E.J., Chung S.R., Na D.G. 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(12):2094–123. DOI: 10.3348/kjr.2021.0713

44. Lee J.Y., Yoo R.E., Rhim J.H. et al. Validation of ultrasound risk stratification systems for cervical lymph node metastasis in patients with thyroid cancer. Cancers 2022;14(9):2106.