Diagnostic Clues for Thyroid Aspiration Cytology

  • Aki TanakaEmail author
  • Ayana Suzuki
  • Miyoko Higuchi
  • Mitsuyoshi Hirokawa


Concerning a diagnosis of thyroid fine needle aspiration cytology (FNAC), we should understand that there is no pathognomonic finding. For instance, it is well known that intranuclear cytoplasmic inclusions are frequently seen in papillary thyroid carcinoma cases and are characteristic of the tumor, but they are also observed in other thyroid conditions, such as hyalinizing trabecular tumor, medullary thyroid carcinoma, anaplastic thyroid carcinoma, and so on. Therefore, practically, we have to find as many diagnostic clues as possible and make a differential diagnosis by analyzing them comprehensively. In this chapter, we introduce diagnostic clues for thyroid FNAC that will be very helpful for beginners.


  1. 1.
    DeMay RM. Thyroid. In: The art and science of cytopathology. 2nd edit. Volume 2, Superficial aspiration cytology. Chicago: ASCP Press; 2012. p. 860–924.Google Scholar
  2. 2.
    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
  3. 3.
    Fadda G, Rossi ED, Raffaelli M, et al. Fine-needle aspiration biopsy of thyroid lesions processed by thin-layer cytology: one-year institutional experience with histologic correlation. Thyroid. 2006;16:975–81.CrossRefGoogle Scholar
  4. 4.
    Löwhagen T, Granberg PO, Lundell G, et al. Aspiration biopsy cytology (ABC) in nodules of the thyroid gland suspected to be malignant. Surg Clin North Am. 1979;9:3–18.CrossRefGoogle Scholar
  5. 5.
    Basu D, Jayaram G. A logistic model for thyroid lesions. Diagn Cytopathol. 1992;8:23–7.CrossRefGoogle Scholar
  6. 6.
    Khurana R, Agarwal A, Bajpai VK, et al. Unraveling the amyloid associated with human medullary thyroid carcinoma. Endocrinology. 2004;145:5465–70.CrossRefGoogle Scholar
  7. 7.
    Albores-Saavedra J, LiVolsi VA, Williams ED. Medullary carcinoma. Semin Diagn Pathol. 1985;2:137–46.PubMedGoogle Scholar
  8. 8.
    Bose S, Kapila K, Verma K. Medullary carcinoma of the thyroid: a cytological, immunocytochemical and ultrastructural study. Diagn Cytopathol. 1992;8:28–32.CrossRefGoogle Scholar
  9. 9.
    Nobuoka Y, Hirokawa M, Kuma S, Takagi N, Higuchi M, Masuoka H, et al. Cytological findings and differential diagnoses of primary thyroid MALT lymphoma with striking plasma cell differentiation and amyloid deposition. Diagn Cytopathol. 2014;42:73–7.CrossRefGoogle Scholar
  10. 10.
    Elsheikh TM. The Bethesda system for reporting thyroid cytopathology, 2nd edit. USA: Springer; 2018. p. 40–8.Google Scholar
  11. 11.
    Layfield LJ, Kakudo K. The Bethesda system for reporting thyroid cytopathology, 2nd edit. USA: Springer; 2018. p. 213–8.Google Scholar
  12. 12.
    Das DK, Mallik MK, Haji BE, et al. Psammoma body and itsprecursors in papillary thyroid carcinoma: a study by fine-needle aspiration cytology. Diagn Cytopathol. 2004;31:380–6.CrossRefGoogle Scholar
  13. 13.
    Johannessen JV, Sobrinho-Simões M. The originand significance of thyroid psammoma bodies. Lab Investig. 1980;43:287–96.PubMedGoogle Scholar
  14. 14.
    Klinck GH, Winship T. Psammomabodiesand thyroid cancer. Cancer. 1959;12:656–62.CrossRefGoogle Scholar
  15. 15.
    Rosai J. Papillary carcinoma. Monogr Pathol. 1993;35:138–65.Google Scholar
  16. 16.
    Das DK, Sheikh ZA, George SS, et al. Papillary thyroid carcinoma: evidence for intracytoplasmic formation of precursor substance for calcification and its release from well-preserved neoplastic cells. Diagn Cytopathol. 2008;36:809–12.CrossRefGoogle Scholar
  17. 17.
    Vikranth V, Sushma C. Infarction of Hürthle cell tumor of thyroid following fine needle aspiration. J Case Rep. 2017;4:338–40.Google Scholar
  18. 18.
    Ali SZ, Cibas ES. The Bethesda system for reporting thyroid cytopathology: Definitions, criteria and explanatory notes. New York: Springer; 2010. p. 15–51.CrossRefGoogle Scholar
  19. 19.
    Harach HR, Soto MS, Zusman SB, et al. Parenchymatous thyroid nodules: a histocytological study of 31 cases from a goitrous area. J Clin Pathol. 1992;45:25–9.CrossRefGoogle Scholar
  20. 20.
    Szporn AH, Yuan S, Wu M, Burstein DE. Cellular swirls in fine needle aspirates of papillary thyroid carcinoma: a new diagnostic criterion. Mod Pathol. 2006;19:1470–3.CrossRefGoogle Scholar
  21. 21.
    Ricardo VL, Robert YO, Günter K, Juan R, et al. WHO classification of tumours of endocrine organs. Lyon: WHO; 2017. p. 87.Google Scholar
  22. 22.
    Takagi N, Hirokawa M, Nobuoka Y, Higuchi M, Kuma S, et al. Diffuse sclerosing variant of papillary thyroid carcinoma: a study of fine needle aspiration cytology in 20 patients. Cytopathology. 2014;25:199–204.CrossRefGoogle Scholar
  23. 23.
    Lee SH, Jung CK, Bae JS, Jung SL, Choi YJ, et al. Liquid-based cytology improves preoperative diagnostic accuracy of the tall cell variant of papillary thyroid carcinoma. Diagn Cytopathol. 2014;42:23–7.CrossRefGoogle Scholar
  24. 24.
    Hirokawa M, Kanahara T, Habara T, Fujimura N, Horiguchi H, Wakatsuki S, et al. Dilated rough endoplasmic reticulum corresponding to septate cytoplasmic vacuoles in papillary thyroid carcinoma. Diagn Cytopathol. 2000;23:351–3.CrossRefGoogle Scholar
  25. 25.
    Tsuchiya S. Intracytoplasmic lumina of human breast cancer–amicroscopic study and practical application in cytological diagnosis. Acta Pathol Jpn. 1981;31:45–54.PubMedGoogle Scholar
  26. 26.
    Suzuki A, Hirokawa M, Takada N, Masuoka H, Miyauchi A. Thyroid follicular adenoma with numerous intracytoplasmic lumina mimicking yellow bodies: a case report. Cytopathology. 2016;27(6):495–8.CrossRefGoogle Scholar
  27. 27.
    Christ ML, Haja J. Intranuclear cytoplasmic inclusions (invaginations) in thyroid aspirations. Frequency and specificity. Acta Cytol. 1979;23:327–31.PubMedGoogle Scholar
  28. 28.
    Kini SR. Color atlas of differential diagnosis in exfoliative and aspiration cytopathology. Philadelphia: Lippincott Williams & Wilkins; 1999. p. 271.Google Scholar
  29. 29.
    Kini SR. Color atlas of differential diagnosis in exfoliative and aspiration cytopathology. Philadelphia: Lippincott Williams & Wilkins; 1999. p. 251.Google Scholar
  30. 30.
    DeLellis RA. Orphan annie eye nuclei: A historical note. Am J Surg Pathol. 1993;17:1067–72.CrossRefGoogle Scholar
  31. 31.
    Albores-Saavedra J, Wu J. The many faces and mimics of papillary thyroid carcinoma. Endocr Pathol. 2006;17:1–18.CrossRefGoogle Scholar
  32. 32.
    Suzuki A, Hirokawa M, Higuchi M. Cytological characteristics of papillary thyroid carcinoma on LBC specimens, compared with conventional specimens. Diagn Cytopathol. 2015;43:108–13.CrossRefGoogle Scholar
  33. 33.
    Kaneko C, Shamoto M, Niimi H, et al. Studies on intranuclear inclusions and nuclear grooves in papillary thyroid cancer by light, scanning electron and transmission electron microscopy. Acta Cytol. 1996;40:417–22.CrossRefGoogle Scholar
  34. 34.
    Serra S, Asa SL. Controversies in thyroid pathology: the diagnosis of follicular neoplasms. Endocr Pathol. 2008;19:156–65.CrossRefGoogle Scholar
  35. 35.
    Carney JA, Ryan J, Goellner JR. Hyalinizing trabecular adenoma of the thyroid gland. Am J Surg Pathol. 1987;11:583–91.CrossRefGoogle Scholar
  36. 36.
    Solomon A, Gupta PK, LiVolsi VA, et al. Distinguishing tall cell variant of papillary thyroid carcinoma from usual variant of papillary thyroid carcinoma in cytologic specimens. Diagn Cytopathol. 2002;27:143–8.CrossRefGoogle Scholar
  37. 37.
    Das DK. Intranuclear cytoplasmic inclusions in fine-needle aspiration smears of papillary thyroid carcinoma: a study of its morphological forms, association with nuclear grooves, and mode of formation. Diagn Cytopathol. 2005;32:264–8.CrossRefGoogle Scholar
  38. 38.
    Bhambhani S, Kashyap V, Das DK. Nuclear grooves: Valuable diagnostic feature in May-Grünwald-Giemsa-stained fine needle aspirates of papillary carcinoma of the thyroid. Acta Cytol. 1990;34:809–12.PubMedGoogle Scholar
  39. 39.
    Miller TR, Bottles K, Holly E, et al. A stepwise logistic regression analysis of papillary carcinoma of the thyroid. Acta Cytol. 1986;30:285–93.PubMedGoogle Scholar
  40. 40.
    Hirokawa M, Odawara Y, Kanahara T. Cytological findings corresponding to overlapping nuclei seen in histological sections. J Jpn Soc Clin Cytol. 1998;37:10–2. [Jpn].CrossRefGoogle Scholar
  41. 41.
    Kini SR. Color atlas of differential diagnosis in exfoliative and aspiration cytopathology. Philadelphia: Lippincott Williams & Wilkins; 1999. p. 280.Google Scholar
  42. 42.
    Hirokawa M, Maekawa M, Kuma S, et al. Cribriform-morular variant of papillary thyroid carcinoma—cytological and immunocytochemical findings of 18 cases. Diagn Cytopathol. 2010;38:890–6.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Aki Tanaka
    • 1
    Email author
  • Ayana Suzuki
    • 1
  • Miyoko Higuchi
    • 1
  • Mitsuyoshi Hirokawa
    • 2
  1. 1.Department of Clinical LaboratoryKuma HospitalKobeJapan
  2. 2.Department of Diagnostic Pathology and CytologyKuma HospitalKobeJapan

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