Thyroid Cancer pp 525-528 | Cite as

Thyroglobulin in Lymph Node Aspirate

  • D. Robert Dufour


Lymph node involvement in patients with differentiated thyroid cancer is an important finding and typically requires further therapy beyond thyroidectomy. While fine-needle aspiration cytology has been considered the gold standard for diagnosis, studies on resected lymph nodes have shown a high rate of false-negative results. Measurement of thyroglobulin in washout fluid from the needle used for aspiration cytology has shown an increased ability to recognize nodal involvement by thyroid cancer. Most studies have used 0.5 mL of saline to wash out the needle, although larger amounts of saline and different fluids have also been used without a discernible difference in diagnostic performance, although matrix effects should be explored. Plain tubes should be used to collect fluid, since false-negative results have been rarely observed with other collection tubes. Since immunometric assays have been used, the possibility of high-dose hook effect causing falsely low results should be evaluated, but has not been to date. Thyroglobulin levels over 1 μg/L (ng/mL) have most commonly been used as the cutoff for considering results indicative of nodal involvement, although there is no consensus on the best cutoff value, and some data suggest that higher cutoff values should be used in lymph node aspirates from patients who have not yet undergone thyroidectomy. The presence of thyroglobulin or heterophile antibodies in serum does not seem to affect results, although this has not been extensively evaluated, and at least two cases with false-negative results revealed after recombinant TSH stimulation have been reported. Diagnostic performance overall typically shows sensitivities and specificities well over 95 %.


Thyroglobulin Thyroglobulin antibodies Heterophile antibodies Immunoassay Interferences Thyroid cancer 


  1. 1.
    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov Y, Pacini F, Randolph G, Sawka A, Shepard D, Sosa J, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Available online at Thyroid 25: DOI:10.1089/thy.2015.0020; print version in Thyroid 26:1–133, 2016.Google Scholar
  2. 2.
    Pacini F, Schlumberger M, Dralle H, et al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol. 2006;154(6):787–803.CrossRefPubMedGoogle Scholar
  3. 3.
    Costante G, Filetti S. Diagnosis: thyroglobulin in fine-needle aspirates-a clue to metastasis? Nat Rev Endocrinol. 2009;5(5):249–50.CrossRefPubMedGoogle Scholar
  4. 4.
    Pacini F, Fugazzola L, Lippi F, et al. Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: a clue to the diagnosis of metastatic differentiated thyroid cancer. J Clin Endocrinol Metab. 1992;74(6):1401–4.PubMedGoogle Scholar
  5. 5.
    Frasoldati A, Toschi E, Zini M, et al. Role of thyroglobulin measurement in fine-needle aspiration biopsies of cervical lymph nodes in patients with differentiated thyroid cancer. Thyroid. 1999;9(2):105–11.CrossRefPubMedGoogle Scholar
  6. 6.
    Venkatraman L, Maxwell P, McCluggage W. Thyroglobulin immunoreactivity in lymph node histiocytes: a potential diagnostic pitfall. J Clin Pathol. 2001;54(4):314–6.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Boi F, Baghino G, Atzeni F, Lai M, Faa G, Mariotti S. The diagnostic value for differentiated thyroid carcinoma metastases of thyroglobulin (Tg) measurement in washout fluid from fine-needle aspiration biopsy of neck lymph nodes is maintained in the presence of circulating anti-Tg antibodies. J Clin Endocrinol Metab. 2006;91(4):1364–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Kim D, Jeon S, Kim C. Usefulness of thyroglobulin measurement in needle washouts of fine-needle aspiration biopsy for the diagnosis of cervical lymph node metastases from papillary thyroid cancer before thyroidectomy. Endocrine. 2012;42(2):399–403.CrossRefPubMedGoogle Scholar
  9. 9.
    Jung JY, Shin JH, Han B-K, Ko EY. Optimized cutoff value and indication for washout thyroglobulin level according to ultrasound findings in patients with well-differentiated thyroid cancer. Am J Neuroradiol. 2013. doi: 10.3174/ajnr.A3687.Google Scholar
  10. 10.
    Suh YJ, Son EJ, Moon HJ, Kim E-K, Han KH, Kwak JY. Utility of thyroglobulin measurements in fine-needle aspirates of space occupying lesions in the thyroid bed after thyroid cancer operations. Thyroid. 2013;23(3):280–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Giovanella L, Ceriani L, Suriano S, Crippa S. Thyroglobulin measurement on fine-needle washout fluids: influence of sample collection methods. Diagn Cytopathol. 2009;37(1):42–4.CrossRefPubMedGoogle Scholar
  12. 12.
    Salmaslıoğlu A, Erbil Y, Çıtlak G, et al. Diagnostic value of thyroglobulin measurement in fine-needle aspiration biopsy for detecting metastatic lymph nodes in patients with papillary thyroid carcinoma. Langenbecks Arch Surg. 2011;396(1):77–81.CrossRefPubMedGoogle Scholar
  13. 13.
    Borel A, Boizel R, Faure P, et al. Significance of low levels of thyroglobulin in fine needle aspirates from cervical lymph nodes of patients with a history of differentiated thyroid cancer. Eur J Endocrinol. 2008;158:691–8.CrossRefPubMedGoogle Scholar
  14. 14.
    St-Jean E, Blain F, Comtois R. High prolactin levels may be missed by immunoradiometric assay in patients with macroprolactinomas. Clin Endocrinol (Oxf). 1996;44(3):305–9.CrossRefGoogle Scholar
  15. 15.
    Giovanella L, Bongiovanni M, Trimboli P. Diagnostic value of thyroglobulin assay in cervical lymph node fine-needle aspirations for metastatic differentiated thyroid cancer. Curr Opin Oncol. 2013;25(1):6–13.CrossRefPubMedGoogle Scholar
  16. 16.
    Cunha N, Rodrigues F, Curado F, et al. Thyroglobulin detection in fine-needle aspirates of cervical lymph nodes: a technique for the diagnosis of metastatic differentiated thyroid cancer. Eur J Endocrinol. 2007;157(1):101–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Sigstad E, Heilo A, Paus E, et al. The usefulness of detecting thyroglobulin in fine-needle aspirates from patients with neck lesions using a sensitive thyroglobulin assay. Diagn Cytopathol. 2007;35(12):761–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Cappelli C, Pirola I, De Martino E, et al. Thyroglobulin measurement in fine-needle aspiration biopsy of metastatic lymph nodes after rhTSH stimulation. Head Neck. 2013;35(1):E21–3.CrossRefPubMedGoogle Scholar
  19. 19.
    Jeon MJ, Park JW, Han JM, et al. Serum antithyroglobulin antibodies interfere with thyroglobulin detection in fine-needle aspirates of metastatic neck nodes in papillary thyroid carcinoma. J Clin Endocrinol Metab. 2013;98(1):153–60.CrossRefPubMedGoogle Scholar
  20. 20.
    Giovanella L, Ghelfo A. Undetectable serum thyroglobulin due to negative interference of heterophile antibodies in relapsing thyroid carcinoma. Clin Chem. 2007;53(10):1871–2.CrossRefPubMedGoogle Scholar
  21. 21.
    Giovanella L. Lymph nodes thyroglobulin measurement after rhTSH stimulation. Head Neck. 2013;35(1):146.CrossRefPubMedGoogle Scholar
  22. 22.
    Lee M, Ross D, Mueller P, Daniels G, Dawson S, Simeone J. Fine-needle biopsy of cervical lymph nodes in patients with thyroid cancer: a prospective comparison of cytopathologic and tissue marker analysis. Radiology. 1993;187(3):851–4.CrossRefPubMedGoogle Scholar
  23. 23.
    Cignarelli M, Ambrosi A, Marino A, et al. Diagnostic utility of thyroglobulin detection in fine-needle aspiration of cervical cystic metastatic lymph nodes from papillary thyroid cancer with negative cytology. Thyroid. 2003;13(12):1163–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Uruno T, Miyauchi A, Shimizu K, et al. Usefulness of thyroglobulin measurement in fine-needle aspiration biopsy specimens for diagnosing cervical lymph node metastasis in patients with papillary thyroid cancer. World J Surg. 2005;29(4):483–5.CrossRefPubMedGoogle Scholar
  25. 25.
    Mikosiński S, Pomorski L, Oszukowska L, et al. The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer. Endokrynol Pol. 2006;57(4):392–5.PubMedGoogle Scholar
  26. 26.
    Snozek C, Chambers E, Reading C, et al. Serum thyroglobulin, high-resolution ultrasound, and lymph node thyroglobulin in diagnosis of differentiated thyroid carcinoma nodal metastases. J Clin Endocrinol Metab. 2007;92(11):4278–81.CrossRefPubMedGoogle Scholar
  27. 27.
    Jeon S, Kim E, Park J, et al. Diagnostic benefit of thyroglobulin measurement in fine-needle aspiration for diagnosing metastatic cervical lymph nodes from papillary thyroid cancer: correlations with US features. Korean J Radiol. 2009;10(2):106–11.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Kim M, Kim E, Kim B, et al. Thyroglobulin measurement in fine-needle aspirate washouts: the criteria for neck node dissection for patients with thyroid cancer. Clin Endocrinol (Oxf). 2009;70(1):145–51.CrossRefGoogle Scholar
  29. 29.
    Bournaud C, Charrié A, Nozières C, et al. Thyroglobulin measurement in fine-needle aspirates of lymph nodes in patients with differentiated thyroid cancer: a simple definition of the threshold value, with emphasis on potential pitfalls of the method. Clin Chem Lab Med. 2010;48(8):1171–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Lee Y, Seo H, Suh S, et al. Cut-off value for needle washout thyroglobulin in athyrotropic patients. Laryngoscope. 2010;120(6):1120–74.PubMedGoogle Scholar
  31. 31.
    Zanella A, Meyer E, Balzan L, et al. Thyroglobulin measurements in washout of fine needle aspirates in cervical lymph nodes for detection of papillary thyroid cancer metastases. Arq Bras Endocrinol Metabol. 2010;54(6):550–4.CrossRefPubMedGoogle Scholar
  32. 32.
    Giovanella L, Ceriani L, Suriano S. Lymph node thyroglobulin measurement in diagnosis of neck metastases of differentiated thyroid carcinoma. J Thyroid Res. 2011. doi: 10.4061/2011/621839.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Sohn Y, Kim M, Kim E, Kwak J. Diagnostic performance of thyroglobulin value in indeterminate range in fine needle aspiration washout fluid from lymph nodes of thyroid cancer. Yonsei Med J. 2012;53(1):126–31.CrossRefPubMedGoogle Scholar
  34. 34.
    Moon JH, Kim YI, Lim JA, et al. Thyroglobulin in washout fluid from lymph node fine-needle aspiration biopsy in papillary thyroid cancer: large-scale validation of the cutoff value to determine malignancy and evaluation of discrepant results. J Clin Endocrinol Metab. 2013;98(3):1061–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Li QK, Nugent SL, Straseski J, et al. Thyroglobulin measurements in fine‐needle aspiration cytology of lymph nodes for the detection of metastatic papillary thyroid carcinoma. Cancer Cytopathol. 2013;121(8):440–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Baldini E, Sorrenti S, Di Gioia C, et al. Cervical lymph node metastases from thyroid cancer: does thyroglobulin and calcitonin measurement in fine needle aspirates improve the diagnostic value of cytology? BMC Clin Pathol. 2013;13(1):7.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Clinical PathologyVeterans Affairs Medical CenterWashington, DCUSA

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