Skip to main content

Advertisement

SpringerLink
Log in

Cytology versus calcitonin assay in fine-needle aspiration biopsy wash-out fluid (FNAB-CT) in diagnosis of medullary thyroid microcarcinoma

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Widespread use of sensitive ultrasound examination led to an increasing detection of medullary thyroid microcarcinoma (micro-MTC). This prospective study evaluated the diagnostic accuracy of Fine-needle Aspiration Biopsy Cytology (FNAB-C) and calcitonin assay in Fine-needle Aspiration Biopsy wash-out fluid (FNAB-CT) in thyroid nodules less than 1 cm with elevated serum calcitonin(sCT).

Methods

87 thyroid nodules from 60 patients with elevated sCT (>10 pg/ml) were included and 51 were thyroid nodules less than 1cm. FNAB-CT and FNAB-C were performed to distinguish medullary thyroid carcinoma (MTC) lesions before surgery, histopathologic diagnoses served as main reference standards.

Results

FNAB-CT had a greater performance over FNAB-C for preoperative diagnosis of MTC (diagnostic accuracy: 98.85 vs 61.90%, sensitivity: 98.55 vs 55.07%, specificity: 100 vs 97.44%), especially for micro-MTC: FNAB-C established a sensitivity and diagnostic accuracy of 48.78 and 58% respectively, while FNAB-CT reached 97.56% sensitivity and 98.04% diagnostic accuracy.

Conclusions

FNAB-CT demonstrated high diagnostic accuracy in diagnosing micro-MTC. Patients with microscopic thyroid nodules and elevated sCT level should perform FNAB-CT to exclude the diagnosis of MTC lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this article.

References

  1. L. Ceolin, M. Duval, A.F. Benini, C.V. Ferreira, A.L. Maia, Medullary thyroid carcinoma beyond surgery: advances, challenges, and perspectives. Endocr. Relat. Cancer 26, R499–R518 (2019)

    Article  CAS  Google Scholar 

  2. H.S. Kazaure, S.A. Roman, J.A. Sosa, Medullary thyroid microcarcinoma: a population-level analysis of 310 patients. Cancer 118, 620–7 (2012)

    Article  Google Scholar 

  3. H. Kwon, W.G. Kim, T.Y. Sung, M.J. Jeon, D.E. Song, Y.M. Lee et al. Changing trends in the clinicopathological features and clinical outcomes of medullary thyroid carcinoma. J. Surg. Oncol. 113, 152–8 (2016)

    Article  Google Scholar 

  4. A. Machens, H. Dralle, Surgical cure rates of sporadic medullary thyroid cancer in the era of calcitonin screening. Eur. J. Endocrinol. 175, 219–28 (2016)

    Article  CAS  Google Scholar 

  5. R.W. Randle, C.J. Balentine, G.E. Leverson, J.A. Havlena, R.S. Sippel, D.F. Schneider et al. Trends in the presentation, treatment, and survival of patients with medullary thyroid cancer over the past 30 years. Surgery 161, 137–146 (2017)

    Article  Google Scholar 

  6. F. Torresan, C. Mian, E. Cavedon, M. Iacobone, Cure and survival of sporadic medullary thyroid carcinoma following systematic preoperative calcitonin screening. Langenbecks Arch. Surg. 404, 411–419 (2019)

    Article  Google Scholar 

  7. N. Choi, W.J. Moon, J.H. Lee, J.H. Baek, D.W. Kim, S.W. Park, Ultrasonographic findings of medullary thyroid cancer: differences according to tumor size and correlation with fine needle aspiration results. Acta Radio. 52, 312–6 (2011)

    Article  Google Scholar 

  8. A. Machens, H. Dralle, Biological relevance of medullary thyroid microcarcinoma. J. Clin. Endocrinol. Metab. 97, 1547–53 (2012)

    Article  CAS  Google Scholar 

  9. G.C. Yang, K. Fried, P.H. Levine, Detection of medullary thyroid microcarcinoma using ultrasound-guided fine needle aspiration cytology. Cytopathology 24, 92–8 (2013)

    Article  CAS  Google Scholar 

  10. J.H. Kim, J.S. Pyo, W.J. Cho, Clinicopathological Significance and Prognosis of Medullary Thyroid Microcarcinoma: A Meta-analysis. World J. Surg. 41, 2551–2558 (2017)

    Article  Google Scholar 

  11. R. Elisei, V. Bottici, F. Luchetti, G. Di Coscio, C. Romei, L. Grasso et al. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J. Clin. Endocrinol. Metab. 89, 163–8 (2004)

    Article  CAS  Google Scholar 

  12. G. Costante, D. Meringolo, C. Durante, D. Bianchi, M. Nocera, S. Tumino et al. Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J. Clin. Endocrinol. Metab. 92, 450–5 (2007)

    Article  CAS  Google Scholar 

  13. G. Costante, D. Meringolo, Calcitonin as a biomarker of C cell disease: recent achievements and current challenges. Endocrine 67, 273–280 (2020)

    Article  CAS  Google Scholar 

  14. H. Vierhapper, B. Niederle, C. Bieglmayer, K. Kaserer, S. Baumgartner-Parzer, Early diagnosis and curative therapy of medullary thyroid carcinoma by routine measurement of serum calcitonin in patients with thyroid disorders. Thyroid 15, 1267–72 (2005)

    Article  CAS  Google Scholar 

  15. S.A. Wells, S.L. Asa, H. Dralle, R. Elisei, D.B. Evans, R.F. Gagel et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25, 567–610 (2015)

    Article  Google Scholar 

  16. I.M. Boschin, F. Torresan, A. Toniato, M. Zane, E.C. Ide, G. Pennelli et al. Incidental medullary thyroid microcarcinoma revealed by mild increase of preoperative serum calcitonin levels: therapeutic implications. Endocrine 45, 448–53 (2014)

    Article  CAS  Google Scholar 

  17. H. Kwon, W.G. Kim, Y.M. Choi, E.K. Jang, M.J. Jeon, D.E. Song et al. A cut-off value of basal serum calcitonin for detecting macroscopic medullary thyroid carcinoma. Clin. Endocrinol. (Oxf.) 82, 598–603 (2015)

    Article  CAS  Google Scholar 

  18. C. Colombo, U. Verga, C. Mian, S. Ferrero, M. Perrino, L. Vicentini et al. Comparison of calcium and pentagastrin tests for the diagnosis and follow-up of medullary thyroid cancer. J. Clin. Endocrinol. Metab. 97, 905–13 (2012)

    Article  CAS  Google Scholar 

  19. M.B. Niederle, C. Scheuba, P. Riss, A. Selberherr, O. Koperek, B. Niederle, Early diagnosis of medullary thyroid cancer: are calcitonin stimulation tests still indicated in the era of highly sensitive calcitonin immunoassays? Thyroid 30, 974–984 (2020)

    Article  CAS  Google Scholar 

  20. C. Nozières, L. Chardon, B. Goichot, F. Borson-Chazot, V. Hervieu, K. Chikh et al. Neuroendocrine tumors producing calcitonin: characteristics, prognosis and potential interest of calcitonin monitoring during follow-up. Eur. J. Endocrinol. 174, 335–41 (2016)

    Article  Google Scholar 

  21. P. Trimboli, G. Treglia, L. Guidobaldi, F. Romanelli, G. Nigri, S. Valabrega et al. Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis. Clin. Endocrinol. (Oxf.) 82, 280–5 (2015)

    Article  Google Scholar 

  22. C.Y. Liu, A. Bychkov, S. Agarwal, Y. Zhu, J.F. Hang, C.R. Lai et al. Cytologic diagnosis of medullary thyroid carcinoma in the Asia-Pacific region. Diagn. Cytopathol. 49, 60–69 (2021)

    Article  Google Scholar 

  23. M.P. Pusztaszeri, M. Bongiovanni, W.C. Faquin, Update on the cytologic and molecular features of medullary thyroid carcinoma. Adv. Anat. Pathol. 21, 26–35 (2014)

    Article  Google Scholar 

  24. K.S. Dyhdalo, D.J. Chute, Barriers to the recognition of medullary thyroid carcinoma on FNA: Implications relevant to the new American Thyroid Association guidelines. Cancer Cytopathol. 126, 397–405 (2018)

    Article  CAS  Google Scholar 

  25. H.J. Moon, E. Son, E.K. Kim, J.H. Yoon, J.Y. Kwak, The diagnostic values of ultrasound and ultrasound-guided fine needle aspiration in subcentimeter-sized thyroid nodules. Ann. Surg. Oncol. 19, 52–9 (2012)

    Article  Google Scholar 

  26. C. Colombo, U. Verga, C. Mian, S. Ferrero, M. Perrino, L. Vicentini et al. Comparison of calcium and pentagastrin tests for the diagnosis and follow-up of medullary thyroid cancer. J. Clin. Endocrinol. Metab. 97, 905–13 (2012)

    Article  CAS  Google Scholar 

  27. F. Boi, I. Maurelli, G. Pinna, F. Atzeni, M. Piga, M.L. Lai et al. Calcitonin measurement in wash-out fluid from fine needle aspiration of neck masses in patients with primary and metastatic medullary thyroid carcinoma. J. Clin. Endocrinol. Metab. 92, 2115–8 (2007)

    Article  CAS  Google Scholar 

  28. T. Kudo, A. Miyauchi, Y. Ito, Y. Takamura, N. Amino, M. Hirokawa, Diagnosis of medullary thyroid carcinoma by calcitonin measurement in fine-needle aspiration biopsy specimens. Thyroid 17, 635–8 (2007)

    Article  Google Scholar 

  29. P. Trimboli, F. Rossi, R. Baldelli, O. Laurenti, G. Nigri, C. Ventura et al. Measuring calcitonin in washout of the needle in patients undergoing fine needle aspiration with suspicious medullary thyroid cancer. Diagn. Cytopathol. 40, 394–8 (2012)

    Article  CAS  Google Scholar 

  30. P. Trimboli, G. Nigri, F. Romanelli, D.D. Cicciarella Modica, A. Crescenzi, S. Valabrega et al. Medullary thyroid nodules by measurement of calcitonin (Ct) in aspiration needle washout in patients with multinodular goiter and moderately elevated serum Ct. Exp. Clin. Endocrinol. Diabetes 120, 234–7 (2012)

    Article  CAS  Google Scholar 

  31. C. Diazzi, B. Madeo, E. Taliani, L. Zirilli, S. Romano, A.R. Granata et al. The diagnostic value of calcitonin measurement in wash-out fluid from fine-needle aspiration of thyroid nodules in the diagnosis of medullary thyroid cancer. Endocr. Pr. 19, 769–79 (2013)

    Article  Google Scholar 

  32. U. Mousa, A. Gursoy, H. Ozdemir, G. Moray, Medullary thyroid carcinoma in a patient with Hashimoto’s thyroiditis diagnosed by calcitonin washout from a thyroid nodule. Diagn. Cytopathol. 41, 644–6 (2013)

    Article  Google Scholar 

  33. P. Trimboli, N. Cremonini, L. Ceriani, E. Saggiorato, L. Guidobaldi, F. Romanelli et al. Calcitonin measurement in aspiration needle washout fluids has higher sensitivity than cytology in detecting medullary thyroid cancer: a retrospective multicentre study. Clin. Endocrinol. (Oxf.) 80, 135–40 (2014)

    Article  CAS  Google Scholar 

  34. C. de Crea, M. Raffaelli, D. Maccora, C. Carrozza, G. Canu, G. Fadda et al. Calcitonin measurement in fine-needle aspirate washouts vs. cytologic examination for diagnosis of primary or metastatic medullary thyroid carcinoma. Acta Otorhinolaryngol. Ital. 34, 399–405 (2014)

    PubMed  Google Scholar 

  35. A. Suzuki, M. Hirokawa, N. Takada, M. Higuchi, A. Ito, N. Yamao et al. Fine-needle aspiration cytology for medullary thyroid carcinoma: a single institutional experience in Japan. Endocr. J. 64, 1099–1104 (2017)

    Article  CAS  Google Scholar 

  36. B. Marques, N. Cunha, R.G. Martins, A.R. Elvas, J. Couto, J. Santos et al. Lymph node metastases of medullary thyroid cancer: role of calcitonin in the washout fluid of fine-needle aspiration. Int J. Endocrinol. 2020, 9267972 (2020)

    Article  Google Scholar 

  37. P.M. Bossuyt, J.B. Reitsma, D.E. Bruns, C.A. Gatsonis, P.P. Glasziou, L. Irwig et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ 351, h5527 (2015)

    Article  Google Scholar 

  38. J.Y. Kwak, K.H. Han, J.H. Yoon, H.J. Moon, E.J. Son, S.H. Park et al. Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology 260, 892–9 (2011)

    Article  Google Scholar 

  39. E.S. Cibas, S.Z. Ali, The 2017 Bethesda system for reporting thyroid cytopathology. Thyroid 27, 1341–1346 (2017)

    Article  Google Scholar 

  40. B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov 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 26, 1–133 (2016)

    Article  Google Scholar 

Download references

Funding

This study was sponsored by the grants from The National Key Research and Development Program of China (2016YFC0901503), National Science Foundation of China (81770782, 81700686). Foundation of Health and Family planning Commission of Shanghai (20174Y0204), State Project for Essential Drug Research and Development from Ministry of Science and Technology (2017ZX09304007002).

Author information

Author notes

  1. These authors contributed equally: Ziyuan Liu, Wenzhong Zhou

Authors and Affiliations

  1. Shanghai Clinical Center for Endocrine & Metabolic Diseases, Department of Endocrine & Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

    Ziyuan Liu, Jie Zhang, Haorong Li, Zhihan Wan, Liyun Shen, Yulin Zhou, Shu Wang & Lei Ye

  2. Shanghai Institute of Endocrine & Metabolic Diseases, Shanghai, China

    Wenzhong Zhou, Rulai Han & Yan Jin

  3. Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

    Wei Zhou

  4. Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

    Xi Chen

Authors
  1. Ziyuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenzhong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rulai Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Haorong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhihan Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yan Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Liyun Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yulin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Xi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Lei Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xi Chen or Lei Ye.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval

This study was approved by the board of medical ethics of Ruijin Hospital, Shanghai Jiaotong University.

Consent to participate

Written informed consents were obtained from all participates included in the study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Z., Zhou, W., Han, R. et al. Cytology versus calcitonin assay in fine-needle aspiration biopsy wash-out fluid (FNAB-CT) in diagnosis of medullary thyroid microcarcinoma. Endocrine 74, 340–348 (2021). https://doi.org/10.1007/s12020-021-02759-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-021-02759-1

Keywords

Search

Navigation