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Cytology of thyroid and parathyroid glands in oncology diagnosis – a contemporary review of updates and innovations

Elwira Beata Bakuła-Zalewska1, Agnieszka Żyłka2, Marek Dedecjus2, Piotr Góralski2, Jacek Gałczyński2, Joanna Długosińska2, Monika Durzyńska1, Monika Prochorec-Sobieszek1, Henryk A. Domanski3


Fine needle aspiration (FNA) is widely used in the examination of head and neck lesions and has been considered an important diagnostic tool in the evaluation of thyroid and parathyroid nodules. Thyroid nodules are frequent findings in the general population, although 90-95% of these nodules are benign. FNA plays a crucial role to determine which nodules are at greatest risk of malignancy and which nodules are benign and do not require surgical intervention. In the case of the parathyroid glands, the US-guided parathyroid FNA is an effective method for the identification of intrathyroidal or ectopic parathyroid tissue, and distinguish it from thyroid and other surrounding anatomical structures. In addition, the use of FNA can significantly increase the accuracy of parathyroid gland location in patients with hyperparathyroidism who are candidates for surgical treatment in cases where imaging techniques fail to identify the parathyroid. Widespread US guidance in FNA procedures, constellation of clearly defined, reproducible key diagnostic cytopathological criteria for individual lesions in conjunction with images and clinical data as well as evolutions in FNA techniques and ancillary tests facilitate further diagnostic and clinical management. This paper aims to review the current state of the art in cytological evaluation of thyroid and parathyroid lesions.

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  1. Ogilvie JB, Piatigorsky EJ, Clark OH. Current status of fine needle aspiration for thyroid nodules. Adv Surg. 2006; 40: 223–238.
  2. Sclabas GM, Staerkel GA, Shapiro SE, et al. Fine-needle aspiration of the thyroid and correlation with histopathology in a contemporary series of 240 patients. Am J Surg. 2003; 186(6): 702–9; discussion 709.
  3. Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med. 1993; 118(4): 282–289.
  4. Guilmette J, Sadow PM. Parathyroid Pathology. Surg Pathol Clin. 2019; 12(4): 1007–1019.
  5. Cooper DS, Doherty GM, Haugen BR, et al. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009; 19(11): 1167–1214.
  6. Luster M, Aktolun C, Amendoeira I, et al. European Perspective on 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: Proceedings of an Interactive International Symposium. Thyroid. 2019; 29(1): 7–26.
  7. Suzuki A, Hirokawa M, Kanematsu R, et al. Fine-needle aspiration of parathyroid adenomas: Indications as a diagnostic approach. Diagn Cytopathol. 2021; 49(1): 70–76.
  8. Patel KN, Yip L, Lubitz CC, et al. The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults. Ann Surg. 2020; 271(3): e21–e93.
  9. Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism. JAMA Surg. 2016; 151(10): 959–968.
  10. Park JiY, Choi W, Hong AR, et al. A Comprehensive Assessment of the Harms of Fine-Needle Aspiration Biopsy for Thyroid Nodules: A Systematic Review. Endocrinol Metab (Seoul). 2023; 38(1): 104–116.
  11. Alwaheeb S, Rambaldini G, Boerner S, et al. Worrisome histologic alterations following fine-needle aspiration of the parathyroid. J Clin Pathol. 2006; 59(10): 1094–1096.
  12. Hirokawa M, Suzuki A, Higuchi M, et al. Histological alterations following fine-needle aspiration for parathyroid adenoma: Incidence and diagnostic problems. Pathol Int. 2021; 71(6): 400–405.
  13. Kim J, Horowitz G, Hong M, et al. The dangers of parathyroid biopsy. J Otolaryngol Head Neck Surg. 2017; 46(1): 4.
  14. Spinelli C, Bonadio AG, Berti P, et al. Cutaneous spreading of parathyroid carcinoma after fine needle aspiration cytology. J Endocrinol Invest. 2000; 23(4): 255–257.
  15. Agarwal G, Dhingra S, Mishra SK, et al. Implantation of parathyroid carcinoma along fine needle aspiration track. Langenbecks Arch Surg. 2006; 391(6): 623–626.
  16. Bakuła-Zalewska E, Długosińska J, Stanek-Widera A, et al. Fine needle aspiration biopsy of parathyroid; is it meaningful? A cytologic study of 81 cases with histological and clinical correlations. Cytopathology. 2024; 35(3): 362–370.
  17. Caleo A, Vitale M, Valvano L, et al. Fine needle cytology pre-surgical differentiation of parathyroid neoplasms: Is it reliable? Cytopathology. 2017; 28(4): 273–279.
  18. Tseng FY, Hsiao YL, Chang TC. Ultrasound-guided fine needle aspiration cytology of parathyroid lesions. A review of 72 cases. Acta Cytol. 2002; 46(6): 1029–1036.
  19. Abraham D, Sharma PK, Bentz J, et al. Utility of ultrasound-guided fine-needle aspiration of parathyroid adenomas for localization before minimally invasive parathyroidectomy. Endocr Pract. 2007; 13(4): 333–337.
  20. Li W, Zhu Q, Lai X, et al. Value of preoperative ultrasound-guided fine-needle aspiration for localization in Tc-99m MIBI-negative primary hyperparathyroidism patients. Medicine (Baltimore). 2017; 96(49): e9051.
  21. Obołończyk Ł, Karwacka I, Wiśniewski P, et al. The Current Role of Parathyroid Fine-Needle Biopsy (P-FNAB) with iPTH-Washout Concentration (iPTH-WC) in Primary Hyperparathyroidism: A Single Center Experience and Literature Review. Biomedicines. 2022; 10(1).
  22. Lew JI, Snyder RA, Sanchez YM, et al. Fine needle aspiration of the thyroid: correlation with final histopathology in a surgical series of 797 patients. J Am Coll Surg. 2011; 213(1): 188–94; discussion 194.
  23. Porterfield JR, Grant CS, Dean DS, et al. Reliability of benign fine needle aspiration cytology of large thyroid nodules. Surgery. 2008; 144(6): 963–8; discussion 968.
  24. Hegedüs L. Clinical practice. The thyroid nodule. N Engl J Med. 2004; 351(17): 1764–1771.
  25. Bouvet M, Feldman JI, Gill GN, et al. Surgical management of the thyroid nodule: patient selection based on the results of fine-needle aspiration cytology. Laryngoscope. 1992; 102(12 Pt 1): 1353–1356.
  26. Goldfarb M, Gondek S, Solorzano C, et al. Surgeon-performed ultrasound can predict benignity in thyroid nodules. Surgery. 2011; 150(3): 436–441.
  27. Yassa L, Cibas ES, Benson CB, et al. Long-term assessment of a multidisciplinary approach to thyroid nodule diagnostic evaluation. Cancer. 2007; 111(6): 508–516.
  28. Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2013. Canadian Cancer Society, Toronto 2013.
  29. Elisei R, Molinaro E, Agate L, et al. Are the clinical and pathological features of differentiated thyroid carcinoma really changed over the last 35 years? Study on 4187 patients from a single Italian institution to answer this question. J Clin Endocrinol Metab. 2010; 95(4): 1516–1527.
  30. Roy R, Kouniavsky G, Venkat R, et al. The role of preoperative neck ultrasounds to assess lymph nodes in patients with suspicious or indeterminate thyroid nodules. J Surg Oncol. 2012; 105(6): 601–605.
  31. Wang CCC, Friedman L, Kennedy GC, et al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid. 2011; 21(3): 243–251.
  32. Nagataki S, Nyström E. Epidemiology and primary prevention of thyroid cancer. Thyroid. 2002; 12(10): 889–896.
  33. Feldt-Rasmussen U. Iodine and cancer. Thyroid. 2001; 11(5): 483–486.
  34. Lee JH, Hwang Y, Song RY, et al. Relationship between iodine levels and papillary thyroid carcinoma: A systematic review and meta-analysis. Head Neck. 2017; 39(8): 1711–1718.
  35. Ron E, Lubin J, Shore R, et al. Thyroid Cancer after Exposure to External Radiation: A Pooled Analysis of Seven Studies. Radiat Res. 1995; 141(3): 259–277.
  36. Mirkatouli NB, Hirota S, Yoshinaga S. Thyroid cancer risk after radiation exposure in adults-systematic review and meta-analysis. J Radiat Res. 2023; 64(6): 893–903.
  37. de Vathaire F, Zidane M, Xhaard C, et al. Assessment of Differentiated Thyroid Carcinomas in French Polynesia After Atmospheric Nuclear Tests Performed by France. JAMA Netw Open. 2023; 6(5): e2311908.
  38. Baloch ZW, Asa SL, Barletta JA, et al. Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr Pathol. 2022; 33(1): 27–63.
  39. Nikiforov YE. RET/PTC rearrangement in thyroid tumors. Endocr Pathol. 2002; 13(1): 3–16.
  40. Khan MS, Qadri Q, Makhdoomi MJ, et al. RET/PTC Gene Rearrangements in Thyroid Carcinogenesis: Assessment and Clinico-Pathological Correlations. Pathol Oncol Res. 2020; 26(1): 507–513.
  41. Agrawal N, Akbani R, Aksoy B, et al. Integrated Genomic Characterization of Papillary Thyroid Carcinoma. Cell. 2014; 159(3): 676–690.
  42. Abdullah MI, Junit SM, Ng KL, et al. Papillary Thyroid Cancer: Genetic Alterations and Molecular Biomarker Investigations. Int J Med Sci. 2019; 16(3): 450–460.
  43. Rajab M, Payne RJ, Forest VI, et al. Molecular Testing for Thyroid Nodules: The Experience at McGill University Teaching Hospitals in Canada. Cancers (Basel). 2022; 14(17).
  44. Ciampi R, Romei C, Ramone T, et al. Genetic Landscape of Somatic Mutations in a Large Cohort of Sporadic Medullary Thyroid Carcinomas Studied by Next-Generation Targeted Sequencing. iScience. 2019; 20: 324–336.
  45. Tessler FN, Middleton WD, Grant EG, et al. ACR Thyroid Imaging, Reporting and Data System (TI-RADS): White Paper of the ACR TI-RADS Committee. J Am Coll Radiol. 2017; 14(5): 587–595.
  46. Chen F, Sun Y, Chen G, et al. The Diagnostic Efficacy of the American College of Radiology (ACR) Thyroid Imaging Report and Data System (TI-RADS) and the American Thyroid Association (ATA) Risk Stratification Systems for Thyroid Nodules. Comput Math Methods Med. 2022; 2022: 9995962.
  47. Russ G, Bonnema SJ, Erdogan MF, et al. European Thyroid Association Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults: The EU-TIRADS. Eur Thyroid J. 2017; 6(5): 225–237.
  48. Middleton WD, Teefey SA, Reading CC, et al. Comparison of Performance Characteristics of American College of Radiology TI-RADS, Korean Society of Thyroid Radiology TIRADS, and American Thyroid Association Guidelines. AJR Am J Roentgenol. 2018; 210(5): 1148–1154.
  49. Jarząb B, Dedecjus M, Lewiński A, et al. Diagnosis and treatment of thyroid cancer in adult patients - Recommendations of Polish Scientific Societies and the National Oncological Strategy. 2022 Update [Diagnostyka i leczenie raka tarczycy u chorych dorosłych - Rekomendacje Polskich Towarzystw Naukowych oraz Narodowej Strategii Onkologicznej. Aktualizacja na rok 2022]. Endokrynol Pol. 2022; 73(2): 173–300.
  50. Ruda JM, Hollenbeak CS, Stack BC. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg. 2005; 132(3): 359–372.
  51. Rao SD. Epidemiology of parathyroid disorders. Best Pract Res Clin Endocrinol Metab. 2018; 32(6): 773–780.
  52. Domanski HA, Qian X, Stanley DE. Chapter 1. Introduction; VanderLaan PA, Krane JF. Chapter 5: Head and Neck: Thyroid. In: Domanski HA. ed. Atlas of fine needle aspiration cytology. 2nd ed. Springer, London 2019.
  53. Ghaheri BA, Koslin DB, Wood AH, et al. Preoperative ultrasound is worthwhile for reoperative parathyroid surgery. Laryngoscope. 2004; 114(12): 2168–2171.
  54. Petranović Ovčariček P, Giovanella L, Carrió Gasset I, et al. The EANM practice guidelines for parathyroid imaging. Eur J Nucl Med Mol Imaging. 2021; 48(9): 2801–2822.
  55. Feletti F, Mellini L, Pironi F, et al. Role of the cytopathologist during the procedure of fine-needle aspiration biopsy of thyroid nodules. Insights Imaging. 2021; 12(1): 111.
  56. Witt BL, Schmidt RL. Rapid onsite evaluation improves the adequacy of fine-needle aspiration for thyroid lesions: a systematic review and meta-analysis. Thyroid. 2013; 23(4): 428–435.
  57. Zargham R, Johnson H, Anderson S, et al. Conditions associated with the need for additional needle passes in ultrasound-guided thyroid fine-needle aspiration with rapid on-site pathology evaluation. Diagn Cytopathol. 2021; 49(1): 105–108.
  58. Hambleton C, Kandil E. Appropriate and accurate diagnosis of thyroid nodules: a review of thyroid fine-needle aspiration. Int J Clin Exp Med. 2013; 6(6): 413–422.
  59. Cesur M, Corapcioglu D, Bulut S, et al. Comparison of palpation-guided fine-needle aspiration biopsy to ultrasound-guided fine-needle aspiration biopsy in the evaluation of thyroid nodules. Thyroid. 2006; 16(6): 555–561.
  60. Robitschek J, Straub M, Wirtz E, et al. Diagnostic efficacy of surgeon-performed ultrasound-guided fine needle aspiration: a randomized controlled trial. Otolaryngol Head Neck Surg. 2010; 142(3): 306–309.
  61. Ali SZ, VanderLaan PA. The Bethesda System for ReportingThyroid Cytopathology: Definitions, Criteria, and Explana-tory Notes, 3rd ed. Springer, New York 2023.
  62. Ali SZ, Baloch ZW, Cochand-Priollet B, et al. The 2023 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2023; 33(9): 1039–1044.
  63. Crescenzi A, Baloch Z. Immunohistochemistry in the pathologic diagnosis and management of thyroid neoplasms. Front Endocrinol (Lausanne). 2023; 14: 1198099.
  64. Nishino M, Krane JF. Role of Ancillary Techniques in Thyroid Cytology Specimens. Acta Cytol. 2020; 64(1-2): 40–51.
  65. Baloch Z, Mete O, Asa SL. Immunohistochemical Biomarkers in Thyroid Pathology. Endocr Pathol. 2018; 29(2): 91–112.
  66. Bongiovanni M, Spitale A, Faquin WC, et al. The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol. 2012; 56(4): 333–339.
  67. Schneider DF, Cherney Stafford LM, Brys N, et al. GAUGING THE EXTENT OF THYROIDECTOMY FOR INDETERMINATE THYROID NODULES: AN ONCOLOGIC PERSPECTIVE. Endocr Pract. 2017; 23(4): 442–450.
  68. Tysarowski A, Szumera-Ciećkiewicz A, Marszałek A, et al. Molecular diagnostics of cancers – practical approach. Nowotwory. Journal of Oncology. 2023; 73(3): 174–186.
  69. Ferraz C. Molecular testing for thyroid nodules: Where are we now? Rev Endocr Metab Disord. 2024; 25(1): 149–159.
  70. Trimboli P, Scappaticcio L, Treglia G, et al. Testing for BRAF (V600E) Mutation in Thyroid Nodules with Fine-Needle Aspiration (FNA) Read as Suspicious for Malignancy (Bethesda V, Thy4, TIR4): a Systematic Review and Meta-analysis. Endocr Pathol. 2020; 31(1): 57–66.
  71. Rivera M, Ricarte-Filho J, Knauf J, et al. Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns. Mod Pathol. 2010; 23(9): 1191–1200.
  72. Agarwal S, Bychkov A, Jung CK. Emerging Biomarkers in Thyroid Practice and Research. Cancers (Basel). 2021; 14(1).
  73. Giordano TJ. Genomic Hallmarks of Thyroid Neoplasia. Annu Rev Pathol. 2018; 13: 141–162.
  74. Fagin JA, Wells SA. Biologic and Clinical Perspectives on Thyroid Cancer. N Engl J Med. 2016; 375(11): 1054–1067.
  75. Patel KN, Yip L, Lubitz CC, et al. The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults. Ann Surg. 2020; 271(3): e21–e93.
  76. Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism. JAMA Surg. 2016; 151(10): 959–968.
  77. Ha HJ, Kim EJu, Kim JS, et al. Major Clues and Pitfalls in the Differential Diagnosis of Parathyroid and Thyroid Lesions Using Fine Needle Aspiration Cytology. Medicina (Kaunas). 2020; 56(11).
  78. Heo I, Park S, Jung CW, et al. Fine needle aspiration cytology of parathyroid lesions. Korean J Pathol. 2013; 47(5): 466–471.
  79. Agarwal AM, Bentz JS, Hungerford R, et al. Parathyroid fine-needle aspiration cytology in the evaluation of parathyroid adenoma: cytologic findings from 53 patients. Diagn Cytopathol. 2009; 37(6): 407–410.
  80. Cho M, Oweity T, Brandler TC, et al. Distinguishing parathyroid and thyroid lesions on ultrasound-guided fine-needle aspiration: A correlation of clinical data, ancillary studies, and molecular analysis. Cancer Cytopathol. 2017; 125(9): 674–682.
  81. Layfield LJ. Fine needle aspiration cytology of cystic parathyroid lesions. A cytomorphologic overlap with cystic lesions of the thyroid. Acta Cytol. 1991; 35(4): 447–450.
  82. Domingo RP, Ogden LL, Been LC, et al. Identification of parathyroid tissue in thyroid fine-needle aspiration: A combined approach using cytology, immunohistochemical, and molecular methods. Diagn Cytopathol. 2017; 45(6): 526–532.
  83. Owens CL, Rekhtman N, Sokoll L, et al. Parathyroid hormone assay in fine-needle aspirate is useful in differentiating inadvertently sampled parathyroid tissue from thyroid lesions. Diagn Cytopathol. 2008; 36(4): 227–231.
  84. Dimashkieh H, Krishnamurthy S. Ultrasound guided fine needle aspiration biopsy of parathyroid gland and lesions. Cytojournal. 2006; 3: 6.
  85. Paker I, Yilmazer D, Yandakci K, et al. Intrathyroidal oncocytic parathyroid adenoma: a diagnostic pitfall on fine-needle aspiration. Diagn Cytopathol. 2010; 38(11): 833–836.
  86. Abati A, Skarulis MC, Shawker T, et al. Ultrasound-guided fine-needle aspiration of parathyroid lesions: a morphological and immunocytochemical approach. Hum Pathol. 1995; 26(3): 338–343.
  87. Erdogan-Durmus S, Ramazanoglu SR, Barut HY. Diagnostic significance of GATA 3, TTF-1, PTH, chromogranin expressions in parathyroid fine needle aspirations via immuonocytochemical method. Diagn Cytopathol. 2023; 51(7): 449–454.
  88. Shi Y, Brandler TC, Yee-Chang M, et al. Application of GATA 3 and TTF-1 in differentiating parathyroid and thyroid nodules on cytology specimens. Diagn Cytopathol. 2020; 48(2): 128–137.
  89. Knezević-Obad A, Tomić-Brzac H, Zarković K, et al. Diagnostic pitfalls in parathyroid gland cytology. Coll Antropol. 2010; 34(1): 25–29.
  90. Trimboli P, D'Aurizio F, Tozzoli R, et al. Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids. Clin Chem Lab Med. 2017; 55(7): 914–925.
  91. Gökçay Canpolat A, Şahin M, Ediboğlu E, et al. Diagnostic accuracy of parathyroid hormone levels in washout samples of suspicious parathyroid adenomas: A single-centre retrospective cohort study. Clin Endocrinol (Oxf). 2018; 89(4): 489–495.

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