Suspicious for Malignancy

  • Helen H. Wang
  • Armando C. Filie
  • Douglas P. Clark
  • Celeste N. Powers


Most primary thyroid malignancies have distinctive cytologic features and are easily recognizable on fine needle aspiration (FNA). The exceptions are follicular and Hürthle cell carcinomas (addressed in Chaps. 5 and 6). Although the cytologic features of papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), and lymphoma are well-established (see Chaps. 8, 9, and 12), in any given specimen they may be quantitatively and/or qualitatively insufficient for a definitive diagnosis. Reasons for diagnostic uncertainty in such cases include suboptimal sampling or preservation, an unusual variant of PTC and MTC, and overlapping cytomorphologic (particularly nuclear) features with other thyroid conditions. The benign follicular cells in some cases of lymphocytic (Hashimoto) thyroiditis (LT) can be difficult to distinguish from those of PTC, and the lymphoid cells of LT can be difficult to distinguish from those of a lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). A category that conveys a strong suspicion for malignancy, therefore, is a necessity for thyroid FNA, and in the Bethesda System, it is called “Suspicious for Malignancy (SFM).” SFM is a heterogeneous category because it includes a variety of different malignancies. Most SFM cases are suspicious for PTC, although in many published series the type of suspected malignancy is not specified. When specified, the percentage of total thyroid FNA cases that fall into the “suspicious for PTC” category ranges from 2.4% to 7.9%. This category should be used judiciously so that patients are managed as appropriately as possible.


Positive Predictive Value Papillary Thyroid Carcinoma Fine Needle Aspiration Medullary Thyroid Carcinoma Malt Lymphoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Wang HH. Reporting thyroid fine-needle aspiration: Literature review and a proposal. Diagn Cytopathol. 2006;34(1):67-76.CrossRefPubMedGoogle Scholar
  2. 2.
    Gharib H, Goellner JR, Johnson DA. Fine-needle aspiration cytology of the thyroid. A 12-year experience with 11, 000 biopsies. Clin Lab Med. 1993;13(3):699-709.PubMedGoogle Scholar
  3. 3.
    Renshaw AA. Accuracy of thyroid fine-needle aspiration using receiver operator characteristic curves. Am J Clin Pathol. 2001;116(4):477-482.CrossRefPubMedGoogle Scholar
  4. 4.
    Tulecke MA, Wang HH. ThinPrep for cytologic evaluation of follicular thyroid lesions: correlation with histologic findings. Diagn Cytopathol. 2004;30(1):7-13.CrossRefPubMedGoogle Scholar
  5. 5.
    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.CrossRefPubMedGoogle Scholar
  6. 6.
    Zhang Y, Fraser JL, Wang HH. Morphologic predictors of papillary carcinoma on fine-needle aspiration of thyroid with ThinPrep preparations. Diagn Cytopathol. 2001;24(6):378-383.CrossRefPubMedGoogle Scholar
  7. 7.
    Weber D, Brainard J, Chen L. Atypical epithelial cells, cannot exclude papillary carcinoma, in fine needle aspiration of the thyroid. Acta Cytol. 2008;52(3):320-324.PubMedGoogle Scholar
  8. 8.
    Faquin WC, Cibas ES, Renshaw AA. “Atypical” cells in fine-needle aspiration biopsy specimens of benign thyroid cysts. Cancer. 2005;105(2):71-79.CrossRefPubMedGoogle Scholar
  9. 9.
    Smejkal V, Smejkalova E, Rosa M, Zeman V, Smetana K. Cytologic changes simulating malignancy in thyrotoxic goiters treated with carbimazole. Acta Cytol. 1985;29:173-178.PubMedGoogle Scholar
  10. 10.
    Granter SR, Cibas ES. Cytologic findings in thyroid nodules after 131iodine treatment of hyperthyroidism. Am J Clin Pathol. 1997;107:20-25.PubMedGoogle Scholar
  11. 11.
    Centeno BA, Szyfelbein WM, Daniels GH, Vickery AL. Fine-needle aspiration biopsy of the thyroid gland in patients with prior Graves’ disease treated with radioactive iodine: morphologic findings and potential pitfalls. Acta Cytol. 1996;40:1189-1197.PubMedGoogle Scholar
  12. 12.
    Liu J, Singh B, Tallini G, et al. Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity. Cancer. 2006;107(6):1255-1264.CrossRefPubMedGoogle Scholar
  13. 13.
    Das DK, Mallik MK, Sharma P, et al. Papillary thyroid carcinoma and its variants in fine needle aspiration smears A cytomorphologic study with special reference to tall cell variant. Acta Cytol. 2004;48(3):325-336.PubMedGoogle Scholar
  14. 14.
    Gupta S, Sodhani P, Jain S, Kumar N. Morphologic spectrum of papillary carcinoma of the thyroid: role of cytology in identifying the variants. Acta Cytol. 2004;48(6):795-800.PubMedGoogle Scholar
  15. 15.
    Ylagan LR, Dehner LP, Huettner PC, Lu D. Columnar cell variant of papillary thyroid carcinoma Report of a case with cytologic findings. Acta Cytol. 2004;48(1):73-77.PubMedGoogle Scholar
  16. 16.
    Goellner JR, Johnson DA. Cytology of cystic papillary carcinoma of the thyroid. Acta Cytol. 1982;26(6):797-808.PubMedGoogle Scholar
  17. 17.
    Renshaw AA. “Histiocytoid” cells in fine-needle aspirations of papillary carcinoma of the thyroid: frequency and significance of an under-recognized cytologic pattern. Cancer. 2002;96(4):240-243.CrossRefPubMedGoogle Scholar
  18. 18.
    Papotti M, Volante M, Giuliano A, et al. RET/PTC activation in hyalinizing trabecular tumors of the thyroid. Am J Surg Pathol. 2000;24(12):1615-1621.CrossRefPubMedGoogle Scholar
  19. 19.
    DeLellis RA, Lloyd RV, Heitz PU, Eng C, eds. World Health Organization classification of tumours. Pathology and genetics of tumours of endocrine organs. Lyon: IARC Press; 2004.Google Scholar
  20. 20.
    Castro-Gomez L, Cordova-Ramirez S, Duarte-Torres R, Alonso de Ruiz P, Hurtado-Lopez LM. Cytologic criteria of cystic papillary carcinoma of the thyroid. Acta Cytol. 2003;47(4):590-594.PubMedGoogle Scholar
  21. 21.
    Cooper DS, Doherty GM, Haugen BR, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006;16(2):109-142.CrossRefPubMedGoogle Scholar
  22. 22.
    Filie AC, Asa SL, Geisinger KR, et al. Utilization of ancillary studies in thyroid fine needle aspirates: a synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. Diagn Cytopathol. 2008;36(6):438-441.CrossRefPubMedGoogle Scholar
  23. 23.
    Giard RW, Hermans J. Use and accuracy of fine-needle aspiration cytology in histologically proven thyroid carcinoma: an audit using a national nathology database. Cancer. 2000;90(6):330-334.CrossRefPubMedGoogle Scholar
  24. 24.
    Papaparaskeva K, Nagel H, Droese M. Cytologic diagnosis of medullary carcinoma of the thyroid gland. Diagn Cytopathol. 2000;22(6):351-358.CrossRefPubMedGoogle Scholar
  25. 25.
    Zeppa P, Marino G, Troncone G, et al. Fine-needle cytology and flow cytometry immunophenotyping and subclassification of non-Hodgkin lymphoma: a critical review of 307 cases with technical suggestions. Cancer. 2004;102(1):55-65.CrossRefPubMedGoogle Scholar
  26. 26.
    Chhieng DC, Cohen JM, Cangiarella JF. Cytology and immunophenotyping of low- and intermediate-grade B-cell non-Hodgkin’s lymphomas with a predominant small-cell component: a study of 56 cases. Diagn Cytopathol. 2001;24(2):90-97.CrossRefPubMedGoogle Scholar
  27. 27.
    Crapanzano JP, Lin O. Cytologic findings of marginal zone lymphoma. Cancer. 2003;99(5):301-309.CrossRefPubMedGoogle Scholar
  28. 28.
    Matsushima AY, Hamele-Bena D, Osborne BM. Fine-needle aspiration biopsy findings in marginal zone B cell lymphoma. Diagn Cytopathol. 1999;20(4):190-198.CrossRefPubMedGoogle Scholar
  29. 29.
    Lerma E, Arguelles R, Rigla M, et al. Comparative findings of lymphocytic thyroiditis and thyroid lymphoma. Acta Cytol. 2003;47(4):575-580.PubMedGoogle Scholar
  30. 30.
    Chen HI, Akpolat I, Mody DR, et al. Restricted kappa/lambda light chain ratio by flow cytometry in germinal center B cells in Hashimoto thyroiditis. Am J Clin Pathol. 2006;125(1):42-48.PubMedGoogle Scholar
  31. 31.
    Hamburger JI, Husain M. Contribution of intraoperative pathology evaluation to surgical management of thyroid nodules. Endocrinol Metab Clin North Am. 1990;19(3):509-522.PubMedGoogle Scholar
  32. 32.
    Lee TI, Yang HJ, Lin SY, et al. The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer. Thyroid. 2002;12(7):619-626.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Helen H. Wang
    • 1
  • Armando C. Filie
    • 2
  • Douglas P. Clark
    • 3
  • Celeste N. Powers
    • 4
  1. 1.Department of PathologyBeth Israel Deaconess Medical Center and Harvard Medical SchoolBostonUSA
  2. 2.Laboratory of PathologyNational Cancer InstituteBethesdaUSA
  3. 3.Department of PathologyThe Johns Hopkins Medical InstitutionsBaltimoreUSA
  4. 4.Department of Pathology, Medical College of Virginia HospitalsVirginia Common wealth University Medical CenterRichmondUSA

Personalised recommendations