Cytological features of the diagnosis of recurrent nodular hyperplasia of thyroid gland

The study aimed to improve diagnostic approaches to the assessment of recurrent nodal tumours in the remaining thyroid tissue after surgical treatment, incorporating morphological, ultrasound and clinical and anamnestic features. The methodology included the examination of 69 patients with recurrent lesions classified as Bethesda categories III and IV, who underwent fine-needle aspiration core biopsy under ultrasound imaging, Doppler ultrasound with blood flow assessment, histological verification, and immunocytochemical staining. The results showed that in the Bethesda III group, the presence of malignant tumours was confirmed in 37% of cases, while in Bethesda IV only 24%, which casts doubt on the traditional notions of the risk of neoplasia in these categories. The Bethesda III was dominated by signs associated with malignancy: hypoechogenicity (57%), vertical orientation of the nodule (43%), intranodular blood flow (57%), and indistinct or irregular contours (25%). In group IV, follicular adenomas with benign echostructural features were more common (38%). Three morphotypes were identified: proliferative (69.6%), pseudo-recurrent inflammatory fibrous (14.5%) and true neoplastic (13%), with severe cellular atypia recorded in 2.9% of cases. A low correspondence between cytological and histological results (12-16%) was found, which justifies the need for a comprehensive diagnosis. The study determined that the presence of three or more independent risk factors significantly increases the probability of neoplastic transformation. The practical significance of the study is the formation of a multifactorial stratification system that can increase the accuracy of preoperative diagnosis, justify the choice of surgical tactics and reduce the frequency of misdiagnosis in clinical practice

cellular atypia; hypoechoic structure; fibrous transformation; risk stratification; neoplastic transformation

https://doi.org/10.63341/ijmmr/1.2025.95
  1. Buldygina YuV, Zelinskaya AV, Zurnadzhy LYu, Tarashchenko YuM, Shlyakhtych SL, Tronko MD. Morphological features of thyroid benign focal neoplasms in Graves’ disease. Int J Endocrinol. 2022;18(4):213–8. DOI: 10.22141/2224-0721.18.4.2022.1174
  2. Pasko A, Skrypko V. Some aspects of modern diagnosis and surgical tactics in follicular thyroid neoplasms. Arch Clin Med. 2024;30(2):79–82. DOI: 10.21802/ACM.2024.2.16
  3. Hoperia V, Mostiuk O, Dinets A, Sheptukha S, Hubar O, Gorobeiko M. New insights into histopathological features of Warthin-like papillary thyroid carcinoma. Int J Endocrinol. 2023;19(6):428–32. DOI: 10.22141/2224-0721.19.6.2023.1311
  4. Sgró D, Brancatella A, Greco G, Torregrossa L, Piaggi P, Viola N, et al. Cytological and ultrasound features of thyroid nodules correlate with histotypes and variants of thyroid carcinoma. J Clin Endocrinol Metab. 2023;108(11):e1186–92. DOI: 10.1210/CLINEM/DGAD313
  5. Ahn HS, Kim H, Hong MJ. Ultrasonographic and cytologic assessments of follicular neoplasms of the thyroid: Predictive features differentiating follicular carcinoma from follicular adenoma. PLoS ONE. 2022;17(7):e0271437. DOI: 10.1371/JOURNAL.PONE.0271437
  6. Chen J, Ye D, Lv S, Li X, Ye F, Huang Y, et al. Benign thyroid nodules classified as ACR TI-RADS 4 or 5: Imaging and histological features. Eur J Radiol. 2023;175:111261. DOI: 10.1016/J.EJRAD.2023.111261
  7. Grani G, del Gatto V, Cantisani V, Mandel S, Durante C. A reappraisal of suspicious sonographic features of thyroid nodules: Shape is not an independent predictor of malignancy. J Clin Endocrinol Metab. 2023;108(9):e816–22. DOI: 10.1210/CLINEM/DGAD092
  8. Ohori NP, Nishino N. Follicular neoplasm of thyroid revisited: Current differential diagnosis and the impact of molecular testing. Adv Anatomic Pathol. 2022;30(1):11–23. DOI: 10.1097/PAP.0000000000000368
  9. The World Medical Association. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects [Internet]. [cited 2024 June 30]. Available from: https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/
  10. World Health Organization. Good clinical laboratory practice [Internet]. 2009 [cited 2024 June 30]. Available from: https://wkc.who.int/resources/publications/i/item/good-clinical-laboratory-practice-(-gclp)
  11. Categories of diagnoses in cytological examination of the thyroid gland according to the Bethesda terminology system [Internet]. [cited 2024 June 30]. Available from: https://empendium.com/ua/table/027_7596
  12. WHO classification of tumours online [Internet]. [cited 2024 June 30]. Available from: https://tumourclassification.iarc.who.int/welcome/
  13. Kujdowicz M, Januś D, Taczanowska-Niemczuk A, Lankosz MW, Adamek D. Raman spectroscopy as a potential adjunct of thyroid nodule evaluation: A systematic review. Int J Mol Sci. 2023;24(20):15131. DOI: 10.3390/IJMS242015131.
  14. Suster D, Ronen N, Giorgadze T. Oncocytic nodular hyperplasia of the thyroid. Ann Diagn Pathol. 2022;61:152049. DOI: 10.1016/J.ANNDIAGPATH.2022.152049.
  15. Melo M, Ventura M, Cardoso L, da Rocha A, Paiva I, Sobrinho-Simões M, Soares P. Noninvasive follicular thyroid neoplasm with papillary like nuclear feature (NIFTP): Clinical, pathological and molecular update 5 years after the nomenclature revision. Eur J Endocrinol. 2023;188(2):R15–22. DOI: 10.1093/EJENDO/LVAD004.
  16. Macvanin MT, Gluvić ZM, Zarić BL, Essack M, Gao X, Isenovic ER. New biomarkers: Prospect for diagnosis and monitoring of thyroid disease. Front Endocrinol. 2023;14:1218320. DOI: 10.3389/FENDO.2023.1218320
  17. Giovanella L, Campennì A, Tuncel M, Petranović Ovčariček P. Integrated diagnostics of thyroid nodules. Cancers. 2024;16(2):311. DOI: 10.3390/CANCERS16020311
  18. Chatchomchuan W, Thewjitcharoen Y, Krittiyawong S, Nakasatien S, Veerasomboonsin V, Kanchanapituk A, et al. ODP510 pseudolymphoma of the thyroid gland in association with hashimoto’s thyroiditis: A benign lesion in whitish thyroid gland. J Endocr Soc. 2022;6(1):A779. DOI: 10.1210/JENDSO/BVAC150.1610
  19. Ali M, Roshed M, Ali M, Jahan M, Akhter M. Cytological diagnosis of follicular patterned lesion of thyroid nodule and its follow-up histopathology. Mediscope. 2023;10(2):68–77. DOI: 10.3329/MEDISCOPE.V10I2.67995
  20. Xu Z, Vitale A, Keller C, Alkhoory W, Zhang Z, Yuan L. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Prevalence, cyto-histo correlation, and molecular and ultrasonographic profile. Ann Diagn Pathol. 2024;73:152390. DOI: 10.1016/J.ANNDIAGPATH.2024.152390
  21. Haaga E, Kalfeřt D, Ludvíková M, Kholová I. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features is not a cytological diagnosis, but it influences cytological diagnosis outcomes: A systematic review and meta-analysis. Acta Cytol. 2022;66(2):85–105. DOI: 10.1159/000519757
  22. Bhagwat P, Pomplun S. Nuclear features in thyroid cytology: Features helpful for a morphological diagnosis in routine practice. Diagn Histopathol. 2024;30(6):312–23. DOI: 10.1016/J.MPDHP.2024.04.001
  23. Kholová I, Haaga E, Ludvík J, Kalfeřt D, Ludvikova M. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (niftp): Tumour entity with a short history. A review on challenges in our microscopes, molecular and ultrasonographic profile. Diagnostics. 2022;12(2):250. DOI: 10.3390/DIAGNOSTICS12020250
  24. Bernet VJ, Chindris AM. Update on the evaluation of thyroid nodules. J Nucl Med. 2021;62(2):13S–9S. DOI: 10.2967/JNUMED.120.246025
  25. Chouhan L, Manmohan M, Pasoria S, Tavri O. Sonographic, cytological and histopathological characteristics of spectrum of thyroid nodules: A comparative analysis. Int J Sci Res. 2024;13(6):813–9. DOI: 10.21275/SR24610164446
  26. Ito Y, Kawakami M, Hirokawa M, Yamamoto M, Kihara M, Onoda N, et al. Management of thyroid tumors diagnosed cytologically as follicular neoplasms in a high-volume center: Utility of a scoring system using serum thyroglobulin level, tumor size, ultrasound testing, and cytological diagnosis. Endocrine J. 2025;72(2):161–70. DOI: 10.1507/ENDOCRJ.EJ24-0364
  27. Alwelaie Y, Howaidi A, Tashkandi M, Almotairi A, Saied H, Muzzaffar M, et al. Revisiting the cytomorphological features of poorly differentiated thyroid carcinoma: A comparative analysis with indeterminate thyroid fine-needle aspiration samples. J Am Soc Cytopathol. 2023;12(5):331–40. DOI: 10.1016/J.JASC.2023.05.002
  28. Harahap A, Jung C. Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes. J Pathol Transl Med. 2024;58(6):265–82. DOI: 10.4132/JPTM.2024.10.11
  29. Rahmati-Holasoo H, Shokrpoor S, Marandi A. Follicular cell hyperplasia (goitre), adenoma and adenocarcinoma of the thyroid gland in fourlined terapon (Pelates quadrilineatus): Clinical and histopathological study: 2022-2023. J Fish Dis. 2024;48(2):e14048. DOI: 10.1111/JFD.14048
  30. Hall EA, Hartzband P, VanderLaan PA, Nishino M. Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: Implications for molecular testing and surveillance. Cancer Cytopathol. 2023;131(5):313–24. DOI: 10.1002/CNCY.22684
  31. Tang Z, Gao L, Wang X, Zhang J, Zhan W, Zhou W. Metastases to the thyroid gland: Ultrasonographic findings and diagnostic value of fine-needle aspiration cytology. Front Oncol. 2022;12:939965. DOI: 10.3389/FONC.2022.939965
  32. Kumar M, Kumar A, Giri SS, Rabha D, Richa. Correlation of radiological parameters with cytological finding in the diagnosis of thyroid swelling. IP Arch Cytol Histopathol Res. 2022;7(1):9–15. DOI: 10.18231/J.ACHR.2022.003
  33. Townsend J, Perez-Machado M. Navigating diagnostic uncertainty in thyroid nodules: The critical role of cytology and histology in oncocytic and rare patterned lesions. Cytopathology. 2025;36(3):278–80. DOI: 10.1111/CYT.13473
  34. Wu MH, Chen KY, Hsieh MS, Chen A, Chen CN. Risk stratification in patients with follicular neoplasm on cytology: Use of quantitative characteristics and sonographic patterns. Front Endocrinol. 2021;12:614630. DOI: 10.3389/FENDO.2021.614630