Calcitonin measurement in fine-needle washout fluids in detecting medullary thyroid cancer

BACKGROUND: The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy wash-out fluid is a promising tool in the diagnosis of medullary thyroid cancer.

AIMS: We assessed the potential usefulness and the diagnostic significance of Ct-FNAB alone in comparison with cytology in the diagnosis and localization of primary or metastatic MTC.

MATERIALS AND METHODS: For this purpose, we retrospectively examined data from 67 patients with suspicious thyroid nodules and/or lymph nodes who ultimately underwent surgical treatment at the Endocrinology Research Centre in 2015–2020. The primary endpoint of the study was to evaluate the diagnostic accuracy of Ct-FNAB when compared to cytological examination. The secondary endpoint was to determine the optimal diagnostic level for use in clinical practice.

RESULTS: The obtained results showed that high Ct-FNAB concentrations were present in all histologically proven MTC, either in thyroid gland (sensitivity 92.5%, specificity 100%) or neck masses (sensitivity 88.5%, specificity 100%). The optimal diagnostic threshold for Ct-FNAB values from thyroid nodes was > 122 pg/ml, from lymph nodes >35.8 pg/ml.

CONCLUSIONS: Our findings suggest that Ct-FNAB is a highly reliable diagnostic procedure to identify primary and recurrent/metastatic MTC. The actual relevance of this technique in the management of MTC needs further longitudinal studies in a larger number of patients.

1. Bel’cevich DG, Mudunov AM, Vanushko VJe, et al. Medulljarnyj rak shhitovidnoj zhelezy. Klinicheskie rekomendacii. 2020. (In Russ.). Доступно по: https://rae-org.ru/system/files/documents/pdf/medullyarnyy_rak_shchitovidnoy_zhelezy.pdf Ссылка активна на 24.02.2022.

2. Jiménez C, Hu MI-N, Gagel RF. Management of medullary thyroid carcinoma. Endocrinol Metab Clin North Am. 2008;37(2):481-496. doi: https://doi.org/10.1016/j.ecl.2008.03.001

3. Wells SA, Asa SL, Dralle H, et al. Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma. Thyroid. 2015;25(6):567-610. doi: https://doi.org/10.1089/thy.2014.0335

4. Machens A, Hinze R, Thomusch O, Dralle H. Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg. 2002;26(1):22-28. doi: https://doi.org/10.1007/s00268-001-0176-3

5. Scheuba C, Kaserer K, Moritz A, et al. Sporadic hypercalcitoninemia: clinical and therapeutic consequences. Endocr Relat Cancer. 2009;16(1):243-253. doi: https://doi.org/10.1677/ERC-08-0059

6. Costante G, Durante C, Francis Z, et al. Determination of calcitonin levels in C-cell disease: clinical interest and potential pitfalls. Nat Clin Pract Endocrinol Metab. 2009;5(1):35-44. doi: https://doi.org/10.1038/ncpendmet1023

7. Borchhardt KA, Hörl WH, Sunder-Plassmann G. Reversibility of ′secondary hypercalcitoninemia′ after kidney transplantation. Am J Transplant. 2005;5(7):1757-1763. doi: https://doi.org/10.1111/j.1600-6143.2005.00908.x

8. Bevilacqua M, Dominguez LJ, Righini V, et al. Dissimilar PTH, gastrin, and calcitonin responses to oral calcium and peptones in hypocalciuric hypercalcemia, primary hyperparathyroidism, and normal subjects: A useful tool for differential diagnosis. J Bone Miner Res. 2005;21(3):406-412. doi: https://doi.org/10.1359/JBMR.051210

9. Schuetz M, Duan H, Wahl K, et al. T lymphocyte cytokine production patterns in Hashimoto patients with elevated calcitonin levels and their relationship to tumor initiation. Anticancer Res. 2006;26:4591-4596.

10. Trimboli P, Treglia G, Guidobaldi L, et al. Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis. Clin Endocrinol (Oxf). 2015;82(2):280-285. doi: https://doi.org/10.1111/cen.12563

11. Pusztaszeri MP, Bongiovanni M, Faquin WC. Update on the cytologic and molecular features of medullary thyroid carcinoma. Adv Anat Pathol. 2014;21(1):26-35. doi: https://doi.org/10.1097/PAP.0000000000000004

12. Trimboli P, Rossi F, Baldelli R, et al. Measuring calcitonin in washout of the needle in patients undergoing fine needle aspiration with suspicious medullary thyroid cancer. Diagn Cytopathol. 2012;40(5):394-398. doi: https://doi.org/10.1002/dc.21731

13. Boi F, Maurelli I, Pinna G, 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. 2007;92(6):2115-2118. doi: https://doi.org/10.1210/jc.2007-0326

14. Trimboli P, Cremonini N, Ceriani L, 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). 2014;80(1):135-140. doi: https://doi.org/10.1111/cen.12234

15. Kudo T, Miyauchi A, Ito Y, et al. Diagnosis of medullary thyroid carcinoma by calcitonin measurement in fine-needle aspiration biopsy specimens. Thyroid. 2007;17(7):635-638. doi: https://doi.org/10.1089/thy.2006.0338

16. de Crea C, Raffaelli M, Maccora D, et al. Calcitonin measurement in fine-needle aspirate washouts vs. cytologic examination for diagnosis of primary or metastatic medullary thyroid carcinoma. Acta Otorhinolaryngol Ital. 2014;34(6):399-405.

17. Giovanella L, Ceriani L, Bongiovanni M. Calcitonin measurement on fine needle washouts: preanalytical issues and normal reference values. Diagn Cytopathol. 2013;41(3):226-229. doi: https://doi.org/10.1002/dc.22804

18. Preissner CM, Dodge LA, O’Kane DJ, et al. Prevalence of heterophilic antibody interference in eight automated tumor marker immunoassays. Clin Chem. 2005;51(1):208-210. doi: https://doi.org/10.1373/clinchem.2004.040501

19. Leboeuf R, Langlois M-F, Martin M, et al. “Hook Effect” in calcitonin immunoradiometric assay in patients with metastatic medullary thyroid carcinoma: case report and review of the literature. J Clin Endocrinol Metab. 2006;91(2):361-364. doi: https://doi.org/10.1210/jc.2005-1429

20. Boot CS, Mahon BS, Bramhall SR, Clark PM. Validity of carcinoembryonic antigen and carbohydrate antigen 19-9 measurements in pancreatic cyst fluid with a serum-based immunoassay. Clin Chem. 2010;56(8):1351-1352. doi: https://doi.org/10.1373/clinchem.2010.146373