Specimen Adequacy and Non-diagnostic Thyroid Nodules

  • Pichet Sampatanukul
  • Andrey BychkovEmail author


The assessment of adequacy is the first step in the evaluation of a thyroid fine-needle aspiration (FNA) sample. A specimen with adequate cellularity is a key to the success of thyroid cytology because it assures minimal false-negative rate. The adequacy of a thyroid FNA is defined by both the quantity and quality of the cellular and colloid components. According to the Bethesda system for reporting thyroid cytopathology, a specimen is defined as non-diagnostic if it fails to meet the adequacy criteria (at least 6 groups × 10 benign-appearing, well-visualized follicular cells), with exceptions for thyroiditis, abundant colloid, or any degree of atypia. This chapter discusses cytologic criteria of adequacy along with some controversial or currently evolving topics, such as cyst fluid-only aspirates, adequacy in liquid-based preparations, and proposed modifications of the adequacy criteria. A clinically oriented part is devoted to non-diagnostic thyroid nodules and their management. The last section describes some practical hints and techniques to improve adequacy. The chapter is addressed primarily to cytopathologists; however, it would be useful for each member of the thyroid patient care team, including clinicians (FNA operator and physician in charge) and cytotechnologists.


Cytology Fine-needle aspiration Thyroid Adequacy Non-diagnostic Unsatisfactory Ultrasound-guided FNA Rapid on-site evaluation 


  1. 1.
    Nguyen GK, Ginsberg J, Crockford PM. Fine-needle aspiration biopsy cytology of the thyroid. Its value and limitations in the diagnosis and management of solitary thyroid nodules. Pathol Annu. 1991;26(Pt 1):63–91.PubMedGoogle Scholar
  2. 2.
    Clark DP, Faquin WC. In: Rosenthal DL, editor. Thyroid cytopathology. Boston, MA: Springer; 2010. 200 p.CrossRefGoogle Scholar
  3. 3.
    Yeh MW, Demircan O, Ituarte P, Clark OH. False-negative fine-needle aspiration cytology results delay treatment and adversely affect outcome in patients with thyroid carcinoma. Thyroid. 2004;14:207–15. Scholar
  4. 4.
    Kini SR. Thyroid cytopathology: an Atlas and text. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. 513 p.Google Scholar
  5. 5.
    Crothers BA, Henry MR, Firat P, Frates MC, Rossi ED. Nondiagnostic/unsatisfactory. In: Ali SZ, Cibas ES, editors. The Bethesda system for reporting thyroid cytopathology: definitions, criteria, and explanatory notes. 2nd ed. New York: Springer; 2018. p. 7–18.CrossRefGoogle Scholar
  6. 6.
    Pitman MB, Abele J, Ali SZ, Duick D, Elsheikh TM, Jeffrey RB, et al. Techniques for thyroid FNA: a synopsis of the National cancer institute thyroid fine-needle aspiration state of the science conference. Diagn Cytopathol. 2008;36:407–24. Scholar
  7. 7.
    Pusztaszeri M, Rossi ED, Auger M, Baloch Z, Bishop J, Bongiovanni M, et al. The Bethesda system for reporting thyroid cytopathology: proposed modifications and updates for the second edition from an international panel. Acta Cytol. 2016;60:399–405. Scholar
  8. 8.
    Goellner JR, Gharib H, Grant CS, Johnson DA. Fine needle aspiration cytology of the thyroid, 1980 to 1986. Acta Cytol. 1987;31:587–90.PubMedGoogle Scholar
  9. 9.
    Mazzaferri EL, de los Santos ET, Rofagha-Keyhani S. Solitary thyroid nodule: diagnosis and management. Med Clin North Am. 1988;72:1177–211.CrossRefGoogle Scholar
  10. 10.
    Hamburger JI, Husain M. Semiquantitative criteria for fine-needle biopsy diagnosis: reduced false-negative diagnoses. Diagn Cytopathol. 1988;4:14–7.CrossRefGoogle Scholar
  11. 11.
    Cibas ES, Ali SZ. The 2017 Bethesda system for reporting thyroid cytopathology. Thyroid. 2017;27:1341–6. Scholar
  12. 12.
    Suen K. Guidelines of The Papanicolaou Society of Cytopathology for the examination of fine-needle aspiration specimens from thyroid nodules: the Papanicolaou Society of Cytopathology Task Force on Standards of Practice. Diagn Cytopathol. 1996;15:84–9.<84::AID-DC18>3.0.CO;2-8.CrossRefGoogle Scholar
  13. 13.
    Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda system for reporting thyroid cytopathology: a meta-analysis. Acta Cytol. 2012;56:333–9. Scholar
  14. 14.
    Sheffield BS, Masoudi H, Walker B, Wiseman SM. Preoperative diagnosis of thyroid nodules using the Bethesda system for reporting thyroid cytopathology: a comprehensive review and meta-analysis. Expert Rev Endocrinol Metab. 2014;9:97–110. Scholar
  15. 15.
    Straccia P, Rossi ED, Bizzarro T, Brunelli C, Cianfrini F, Damiani D, et al. A meta-analytic review of the Bethesda system for reporting thyroid cytopathology: has the rate of malignancy in indeterminate lesions been underestimated? Cancer Cytopathol. 2015;123:713–22. Scholar
  16. 16.
    Ocal IT, Ghofrani M. The Bethesda system for reporting thyroid cytopathology (BSRTC). In: Roman SA, Sosa JA, Solorzano CC, editors. Management of thyroid nodules and differentiated thyroid cancer: a practical guide. 2nd ed. New York: Springer; 2017. p. 59–92.CrossRefGoogle Scholar
  17. 17.
    Satoh S, Yamashita H, Kakudo K. Thyroid cytology: the Japanese system and experience at Yamashita Thyroid Hospital. J Pathol Transl Med. 2017;51:548–54. Scholar
  18. 18.
    Garcia-Pascual L, Barahona MJ, Balsells M, del Pozo C, Anglada-Barcelo J, Casalots-Casado J, et al. Complex thyroid nodules with nondiagnostic fine needle aspiration cytology: histopathologic outcomes and comparison of the cytologic variants (cystic vs. acellular). Endocrine. 2011;39:33–40. Scholar
  19. 19.
    Poller DN, Baloch ZW, Fadda G, Johnson SJ, Bongiovanni M, Pontecorvi A, et al. Thyroid FNA: new classifications and new interpretations. Cancer Cytopathol. 2016;124:457–66. Scholar
  20. 20.
    Michael CW, Pang Y, Pu RT, Hasteh F, Griffith KA. Cellular adequacy for thyroid aspirates prepared by ThinPrep: how many cells are needed? Diagn Cytopathol. 2007;35:792–7. Scholar
  21. 21.
    Afify AM, Liu J, Al-Khafaji BM. Cytologic artifacts and pitfalls of thyroid fine-needle aspiration using ThinPrep: a comparative retrospective review. Cancer. 2001;93:179–86.CrossRefGoogle Scholar
  22. 22.
    Liu X, Cai Y, Wang Z, Cui D, Fan H, Jiang L, et al. Adequacy rate comparison between liquid-based cytology using SurePath versus conventional smears in detecting thyroid malignancies. Int J Clin Exp Pathol. 2016;9:4448–54.Google Scholar
  23. 23.
    Nagarajan N, Schneider EB, Ali SZ, Zeiger MA, Olson MT. How do liquid-based preparations of thyroid fine-needle aspiration compare with conventional smears? An analysis of 5475 specimens. Thyroid. 2015;25:308–13. Scholar
  24. 24.
    Vivero M, Renshaw AA, Krane JF. Adequacy criteria for thyroid FNA evaluated by ThinPrep slides only. Cancer Cytopathol. 2017;125:534–43. Scholar
  25. 25.
    Tulecke MA, Wang HH. ThinPrep for cytologic evaluation of follicular thyroid lesions: correlation with histologic findings. Diagn Cytopathol. 2004;30:7–13. Scholar
  26. 26.
    Biscotti CV, Hollow JA, Toddy SM, Easley KA. ThinPrep versus conventional smear cytologic preparations in the analysis of thyroid fine-needle aspiration specimens. Am J Clin Pathol. 1995;104:150–3.CrossRefGoogle Scholar
  27. 27.
    Renshaw AA. Histologic follow-up of nondiagnostic thyroid fine needle aspirations: implications for adequacy criteria. Diagn Cytopathol. 2012;40(Suppl 1):E13–5. Scholar
  28. 28.
    Wise O, Howard MR. Thyroid cytology: a review of current international reporting systems and emerging developments. Cytopathology. 2016;27:161–7. Scholar
  29. 29.
    Limlunjakorn P, Keelawat S, Bychkov A. Evaluation of thyroid fine needle aspiration cytology by the Bethesda reporting system: a retrospective analysis of rates and outcomes from the King Chulalongkorn Memorial Hospital. J Med Assoc Thail. 2017;100:783–92.Google Scholar
  30. 30.
    Keelawat S, Rangdaeng S, Koonmee S, Jitpasutham T, Bychkov A. Current status of thyroid fine-needle aspiration practice in Thailand. J Pathol Transl Med. 2017;51:565–70. Scholar
  31. 31.
    Abelardo AD. Thyroid fine-needle aspiration practice in the Philippines. J Pathol Transl Med. 2017;51:555–9. Scholar
  32. 32.
    Kim MM, Park HJ, Min HS, Kwon HJ, Jung CK, Chae SW, et al. The use of the Bethesda system for reporting thyroid cytopathology in Korea: a nationwide multicenter survey by the Korean Society of Endocrine Pathologists. J Pathol Transl Med. 2017;51(4):410–7. Scholar
  33. 33.
    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, 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. Scholar
  34. 34.
    Nguyen GK, Lee MW, Ginsberg J, Wragg T, Bilodeau D. Fine-needle aspiration of the thyroid: an overview. Cytojournal. 2005;2:12. Scholar
  35. 35.
    Levine RA, Interlandi J. The procedure of ultrasound-guided percutaneous biopsy of thyroid and cervical lymph nodes: technical steps, pitfalls, and pearls. In: Milas M, Mandel SJ, Langer JE, editors. Advanced thyroid and parathyroid ultrasound. New York: Springer; 2017. p. 309–22.CrossRefGoogle Scholar
  36. 36.
    Horton M, Been L, Starling C, Traweek ST. The utility of cellient cell blocks in low-cellularity thyroid fine needle aspiration biopsies. Diagn Cytopathol. 2016;44:737–41. Scholar
  37. 37.
    Suh CH, Baek JH, Park C, Choi YJ, Lee JH. The role of core needle biopsy for thyroid nodules with initially indeterminate results on previous fine-needle aspiration: a systematic review and meta-analysis. AJNR Am J Neuroradiol. 2017;38:1421–6. Scholar
  38. 38.
    Layfield LJ, Abrams J, Cochand-Priollet B, Evans D, Gharib H, Greenspan F, et al. Post-thyroid FNA testing and treatment options: a synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. Diagn Cytopathol. 2008;36:442–8. Scholar
  39. 39.
    Alexander EK. Improving the approach to non-diagnostic aspirates: learning from each other. Endocrine. 2015;49:575–6. Scholar
  40. 40.
    Yoon JH, Kim EK, Kwak JY, Moon HJ. Non-diagnostic thyroid nodules after application of the Bethesda system: a study evaluating the interval for repeat aspiration for non-diagnostic results. Acta Radiol. 2018;59:305–12. Scholar
  41. 41.
    Brito JP, Castro MR, Dean DS, Fatourechi V, Stan M. Survey of current approaches to non-diagnostic fine-needle aspiration from solid thyroid nodules. Endocrine. 2015;49:745–51. Scholar
  42. 42.
    Orija IB, Hamrahian AH, Reddy SS. Management of nondiagnostic thyroid fine-needle aspiration biopsy: survey of endocrinologists. Endocr Pract. 2004;10:317–23. Scholar
  43. 43.
    Hermansen C, Skovgaard Poulsen H, Jensen J, Langfeldt B, Steenskov V, Frederiksen P, et al. Diagnostic reliability of combined physical examination, mammography, and fine-needle puncture (“triple-test”) in breast tumors. A prospective study. Cancer. 1987;60:1866–71.CrossRefGoogle Scholar
  44. 44.
    Haas S, Trujillo A, Kunstle J. Fine needle aspiration of thyroid nodules in a rural setting. Am J Med. 1993;94:357–61.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Faculty of Medicine, Department of PathologyChulalongkorn UniversityBangkokThailand
  2. 2.Department of PathologyKameda Medical CenterKamogawaJapan

Personalised recommendations