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Value of repeated US-guided fine-needle aspiration (US-FNAB) in the follow-up of benign thyroid nodules: a real-life study based on the MoCyThy (Modena’s Cytology of the Thyroid) DATABASE with a revision of the literature

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Abstract

Purpose

The utility of repeating ultrasound-guided fine-needle aspiration (US-FNAB) in the follow-up of benign (THY2) thyroid nodules is still debated. The aim of this study was to retrospectively investigate the diagnostic value of re-biopsy of thyroid nodules following an initially benign result.

Methods

We retrospectively analyzed US-FNABs performed at the Unit of Endocrinology of Modena from 2006 to 2009. The firstly benign cytological result was compared with the cytological results of subsequent US-FNABs (2nd and/or 3rd) executed on the same nodule.

Results

Among 10449 US-FNABs, 6270 (60%) received a THY2 cytological categorization. Of them, 278 (4.43%) underwent a subsequent US-FNAB: 86.7% maintained the same cytology, 32 (11.5%) changed to THY3 (indeterminate) and 5 (1.8%) to THY4 (suspicious of malignancy). Among the 24 nodules addressed to surgery, 9 (37%) were histologically malignant, with an overall miss rate of 3.2%. Male patients had higher risk of discordant results at subsequent US-FNAB (p = 0.005, OR:3.59, 95%CI:1.453–7.769) while dimensional increase above 5 mm was predictive of concordant benign cytology (p = 0.036, OR:0.249, 95%CI:0.068–0.915). Age, suspicious US characteristics, and distance between US-FNABs resulted not predictive.

Conclusions

Re-biopsy of benign nodules confirmed the benign nature in most cases. In case of discordant cytology, relocation in indeterminate category was the most common. The histological diagnosis of cancer occurred in one quarter of nodules surgically removed, with a low overall clinically significant miss rate. Thus, a small percentage of false negatives exists; males and subjects with US suspicious nodules should be carefully followed-up, considering case by case re-biopsy possibility.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. H. Gharib, E. Papini, Thyroid nodules: clinical importance, assessment, and treatment. Endocrinol. Metab. Clin. North Am. 36, 707–735 (2007). vi

    Article  CAS  PubMed  Google Scholar 

  2. D.S. Cooper, G.M. Doherty, B.R. Haugen, R.T. Kloos, S.L. Lee et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19, 1167–1214 (2009)

    Article  PubMed  Google Scholar 

  3. B. Madeo, G. Brigante, A. Ansaloni, E. Taliani, S. Kaleci et al. The added value of operator’s judgement in thyroid nodule ultrasound classification arising from histologically based comparison of different risk stratification systems. Front Endocrinol. 11, 434 (2020)

    Article  Google Scholar 

  4. D.W. Chen, B.H.H. Lang, D.S.A. McLeod, K. Newbold, M.R. Haymart, Thyroid cancer. Lancet 401, 1531–1544 (2023)

    Article  PubMed  Google Scholar 

  5. J. Yang, V. Schnadig, R. Logrono, P.G. Wasserman, Fine-needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations. Cancer 111, 306–315 (2007)

    Article  PubMed  Google Scholar 

  6. B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel 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  PubMed  PubMed Central  Google Scholar 

  7. H. Gharib, E. Papini, R. Paschke, D.S. Duick, R. Valcavi et al. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: executive summary of recommendations. Endocr. Pract. 16, 468–475 (2010)

    Article  PubMed  Google Scholar 

  8. Jasim S., Dean D.S., Gharib H. (2000) Fine-Needle Aspiration of the Thyroid Gland. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, et al. (eds.) Endotext. MDText.com, Inc. Copyright © 2000-2023, MDText.com, Inc., South Dartmouth (MA):

  9. C. Durante, G. Costante, G. Lucisano, R. Bruno, D. Meringolo et al. The natural history of benign thyroid nodules. JAMA 313, 926–935 (2015)

    Article  CAS  PubMed  Google Scholar 

  10. G. Grani, L. Lamartina, T. Montesano, L. Giacomelli, M. Biffoni et al. Prevalence of thyroid nodules and thyroid cancer in individuals with a first-degree family history of non-medullary thyroid cancer: a cross-sectional study based on sonographic screening. Thyroid 32, 1392–1401 (2022)

    Article  CAS  PubMed  Google Scholar 

  11. A. Lucas, M. Llatjós, I. Salinas, J. Reverter, E. Pizarro et al. Fine-needle aspiration cytology of benign nodular thyroid disease. Value of re-aspiration. Eur. J. Endocrinol. 132, 677–680 (1995)

    Article  CAS  PubMed  Google Scholar 

  12. Z. Baloch, V.A. LiVolsi, P. Jain, R. Jain, I. Aljada et al. Role of repeat fine-needle aspiration biopsy (FNAB) in the management of thyroid nodules. Diagn. Cytopathol. 29, 203–206 (2003)

    Article  PubMed  Google Scholar 

  13. A. Orlandi, A. Puscar, E. Capriata, H. Fideleff, Repeated fine-needle aspiration of the thyroid in benign nodular thyroid disease: critical evaluation of long-term follow-up. Thyroid 15, 274–278 (2005)

    Article  CAS  PubMed  Google Scholar 

  14. A. Belfiore, G.L. La Rosa, Fine-needle aspiration biopsy of the thyroid. Endocrinol. Metab. Clin. North Am. 30, 361–400 (2001)

    Article  CAS  PubMed  Google Scholar 

  15. J.M. Chehade, A.B. Silverberg, J. Kim, C. Case, A.D. Mooradian, Role of repeated fine-needle aspiration of thyroid nodules with benign cytologic features. Endocr. Pract. 7, 237–243 (2001)

    Article  CAS  PubMed  Google Scholar 

  16. F. Illouz, P. Rodien, J.P. Saint-Andre, S. Triau, S. Laboureau-Soares et al. Usefulness of repeated fine-needle cytology in the follow-up of non-operated thyroid nodules. Eur. J. Endocrinol. 156, 303–308 (2007)

    Article  CAS  PubMed  Google Scholar 

  17. V.F. Brauer, P. Eder, K. Miehle, T.D. Wiesner, H. Hasenclever et al. Interobserver variation for ultrasound determination of thyroid nodule volumes. Thyroid 15, 1169–1175 (2005)

    Article  CAS  PubMed  Google Scholar 

  18. J.I. Hamburger, Diagnosis of thyroid nodules by fine needle biopsy: use and abuse. J. Clin. Endocrinol. Metab. 79, 335–339 (1994)

    CAS  PubMed  Google Scholar 

  19. J. van Roosmalen, B. van Hemel, A. Suurmeijer, H. Groen, T. Ruitenbeek et al. Diagnostic value and cost considerations of routine fine-needle aspirations in the follow-up of thyroid nodules with benign readings. Thyroid 20, 1359–1365 (2010)

    Article  PubMed  Google Scholar 

  20. S.H. Merchant, R. Izquierdo, K.K. Khurana, Is repeated fine-needle aspiration cytology useful in the management of patients with benign nodular thyroid disease? Thyroid 10, 489–492 (2000)

    Article  CAS  PubMed  Google Scholar 

  21. M.B. Flanagan, N.P. Ohori, S.E. Carty, J.L. Hunt, Repeat thyroid nodule fine-needle aspiration in patients with initial benign cytologic results. Am. J. Clin. Pathol. 125, 698–702 (2006)

    Article  PubMed  Google Scholar 

  22. Y. Liel, S. Ariad, M. Barchana, Long-term follow-up of patients with initially benign thyroid fine-needle aspirations. Thyroid 11, 775–778 (2001)

    Article  CAS  PubMed  Google Scholar 

  23. P.W. Rosario, S. Purisch, Ultrasonographic characteristics as a criterion for repeat cytology in benign thyroid nodules. Arquivos Bras. Endocrinol. Metab. 54, 52–55 (2010)

    Article  Google Scholar 

  24. P.W. Rosario, M.R. Calsolari, What Is the best criterion for repetition of fine-needle aspiration in thyroid nodules with initially benign cytology? Thyroid 25, 1115–1120 (2015)

    Article  PubMed  Google Scholar 

  25. G. Brigante, M.L. Monzani, M. Locaso, V.L. Gnarini, L. Graziadei et al. De novo lesions frequently develop in adult normal thyroid over almost six years. Front Endocrinol. (Lausanne) 11, 18 (2020)

    Article  PubMed  Google Scholar 

  26. K. Asanuma, S. Kobayashi, K. Shingu, Y. Hama, S. Yokoyama et al. The rate of tumour growth does not distinguish between malignant and benign thyroid nodules. Eur. J. Surg. 167, 102–105 (2001)

    Article  CAS  PubMed  Google Scholar 

  27. Dean D.S., Gharib H. (2000) Fine-Needle Aspiration Biopsy of the Thyroid Gland. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, et al. (eds.) Endotext. MDText.com, Inc., South Dartmouth (MA):

  28. P.A. VanderLaan, E. Marqusee, J.F. Krane, Clinical outcome for atypia of undetermined significance in thyroid fine-needle aspirations: should repeated fna be the preferred initial approach? Am. J. Clin. Pathol. 135, 770–775 (2011)

    Article  PubMed  Google Scholar 

  29. M. Marino, M.L. Monzani, G. Brigante, K. Cioni, B. Madeo et al. High-resolution melting is a sensitive, cost-effective, time-saving technique for BRAF V600E detection in thyroid FNAB washing liquid: a prospective cohort study. Eur. thyroid J. 4, 73–81 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. C. Diazzi, B. Madeo, E. Taliani, L. Zirilli, S. Romano 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, 769–779 (2013)

    Article  Google Scholar 

  31. P. Perros, K. Boelaert, S. Colley, C. Evans, R.M. Evans et al. Guidelines for the management of thyroid cancer. Clin. Endocrinol. 81(Suppl 1), 1–122 (2014)

    Article  CAS  Google Scholar 

  32. E.K. Alexander, S. Hurwitz, J.P. Heering, C.B. Benson, M.C. Frates et al. Natural history of benign solid and cystic thyroid nodules. Ann. Intern. Med. 138, 315–318 (2003)

    Article  PubMed  Google Scholar 

  33. L.Y. Huang, Y.L. Lee, P. Chou, W.Y. Chiu, D. Chu, Thyroid fine-needle aspiration biopsy and thyroid cancer diagnosis: a nationwide population-based study. PLoS One 10, e0127354 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  34. N. Glynn, M.J. Hannon, S. Lewis, P. Hillery, M. Al-Mousa et al. Utility of repeat cytological assessment of thyroid nodules initially classified as benign: clinical insights from multidisciplinary care in an Irish tertiary referral centre. BMC Endocr. Disord. 16, 45 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  35. H.M. Zia-Ul-Hussnain, O. Kgosidialwa, C. Kennedy, M. Quinn, E. Dolan et al. Is repeat fine needle aspiration required in thyroid nodules with initial benign cytology? Results from a large Irish series. BMC Endocr. Disord. 22, 102 (2022)

    Article  PubMed  PubMed Central  Google Scholar 

  36. E. Papini, A. Crescenzi, A. D’Amore, M. Deandrea, A. De Benedictis et al. Italian Guidelines for the Management of Non-Functioning Benign and Locally Symptomatic Thyroid Nodules. Endocr. Metab. Immune Disord. Drug Targets 23, 876–885 (2023)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. F. Maino, A. Bufano, G. Dalmazio, M. Campanile, T. Pilli et al. Validation of American Thyroid Association Ultrasound Risk-Adapted Approach for Repeating Cytology in Benign Thyroid Nodules. Thyroid 31, 446–451 (2021)

    Article  CAS  PubMed  Google Scholar 

  38. J.Y. Kwak, H. Koo, J.H. Youk, M.J. Kim, H.J. Moon et al. Value of US correlation of a thyroid nodule with initially benign cytologic results. Radiology 254, 292–300 (2010)

    Article  PubMed  Google Scholar 

  39. F.F. Maia, P.S. Matos, E.J. Pavin, J. Vassallo, D.E. Zantut-Wittmann, Value of repeat ultrasound-guided fine-needle aspiration in thyroid nodule with a first benign cytologic result: impact of ultrasound to predict malignancy. Endocrine 40, 290–296 (2011)

    Article  CAS  PubMed  Google Scholar 

  40. Y.C. Oertel, L. Miyahara-Felipe, M.G. Mendoza, K. Yu, Value of repeated fine needle aspirations of the thyroid: an analysis of over ten thousand FNAs. Thyroid 17, 1061–1066 (2007)

    Article  PubMed  Google Scholar 

  41. M.F. Erdoğan, N. Kamel, D. Aras, A. Akdoğan, N. Başkal et al. Value of re-aspirations in benign nodular thyroid disease. Thyroid 8, 1087–1090 (1998)

    Article  PubMed  Google Scholar 

  42. L. Scappaticcio, P. Trimboli, S. Iorio, M.I. Maiorino, M. Longo et al. Repeat thyroid FNAC: Inter-observer agreement among high- and low-volume centers in Naples metropolitan area and correlation with the EU-TIRADS. Front Endocrinol. 13, 1001728 (2022)

    Article  Google Scholar 

  43. J.H. Shin, B.K. Han, K. Ko, Y.H. Choe, Y.L. Oh, Value of repeat ultrasound-guided fine-needle aspiration in nodules with benign cytological diagnosis. Acta Radiol. 47, 469–473 (2006)

    Article  CAS  PubMed  Google Scholar 

  44. S.R. Chung, J.H. Baek, H.S. Park, Y.J. Choi, T.Y. Sung et al. Ultrasound-pathology discordant nodules on core-needle biopsy: malignancy risk and management strategy. Thyroid 27, 707–713 (2017)

    Article  CAS  PubMed  Google Scholar 

  45. F. Gabalec, J. Cáp, A. Ryska, T. Vasátko, V. Ceeová, Benign fine-needle aspiration cytology of thyroid nodule: to repeat or not to repeat? Eur. J. Endocrinol. 161, 933–937 (2009)

    Article  CAS  PubMed  Google Scholar 

  46. J.H. Park, H.K. Kim, S.W. Kang, J.J. Jeong, K.H. Nam et al. Second opinion in thyroid fine-needle aspiration biopsy by the Bethesda system. Endocr. J. 59, 205–212 (2012)

    Article  PubMed  Google Scholar 

  47. M. Kizilgul, R. Shrestha, A. Radulescu, M.R. Evasovich, L.A. Burmeister, Thyroid nodules over 4 cm do not have higher malignancy or benign cytology false-negative rates. Endocrine 66, 249–253 (2019)

    Article  CAS  PubMed  Google Scholar 

  48. M.E. Sencar, M. Calapkulu, H. Bostan, D. Sakiz, S. Hepsen et al. Effect of thyroid nodule size on cytology reliability and incidence of malignancy: A large cohort of 1205 patients from a single center. Ann. Endocrinol. 84, 238–241 (2023)

    Article  Google Scholar 

  49. L. Hegedus, Clinical practice. The thyroid nodule. N. Engl. J. Med. 351, 1764–1771 (2004)

    Article  PubMed  Google Scholar 

  50. J.C. Furlan, Y.C. Bedard, I.B. Rosen, Single versus sequential fine-needle aspiration biopsy in the management of thyroid nodular disease. Can. J. Surg. 48, 12–18 (2005)

    PubMed  PubMed Central  Google Scholar 

  51. K. Kuma, F. Matsuzuka, T. Yokozawa, A. Miyauchi, M. Sugawara, Fate of untreated benign thyroid nodules: results of long-term follow-up. World J. Surg. 18, 495–498 (1994). discussion 499

    Article  CAS  PubMed  Google Scholar 

  52. E. Menéndez Torre, J. Pineda Arribas, J.P. Martínez de Esteban, M.T. López Carballo, C. de Miguel et al. Value of repeated fine needle aspiration cytology in patients with nodular goiter. Acta Cytol. 51, 850–852 (2007)

    Article  PubMed  Google Scholar 

  53. B.T. Muldoon, M. Gage, M. Shrestha, A. Stojadinovic, H.B. Burch, An assessment of the outcome of repeat thyroid fine-needle aspiration in nodules previously found to have a benign cytologyThe Endocrine Society’s 95th Annual Meeting and Expo, June 15–18, 2013 – San Francisco. Endocr. Rev. 34, 30 (2019)

    Google Scholar 

  54. J.K. Hoang, W.D. Middleton, A.E. Farjat, J.E. Langer, C.C. Reading et al. Reduction in thyroid nodule biopsies and improved accuracy with American College of Radiology Thyroid Imaging Reporting and Data System. Radiology 287, 185–193 (2018)

    Article  PubMed  Google Scholar 

  55. P. Trimboli, M. Castellana, A. Piccardo, F. Romanelli, G. Grani et al. The ultrasound risk stratification systems for thyroid nodule have been evaluated against papillary carcinoma. A meta-analysis. Rev. Endocr. Metab. Disord. 22, 453–460 (2021)

    Article  PubMed  Google Scholar 

  56. J.K. Hoang, W.D. Middleton, F.N. Tessler, Update on ACR TI-RADS: Successes, challenges, and future directions, from the AJR special series on radiology reporting and data systems. AJR Am. J. Roentgenol. 216, 570–578 (2021)

    Article  PubMed  Google Scholar 

  57. B. Abou Shaar, M. Meteb, G. Awad El-Karim, Y. Almalki, Reducing the number of unnecessary thyroid nodule biopsies With the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS). Cureus 14, e23118 (2022)

    PubMed  PubMed Central  Google Scholar 

  58. G. Grani, L. Lamartina, V. Ascoli, D. Bosco, M. Biffoni et al. Reducing the number of unnecessary thyroid biopsies while improving diagnostic accuracy: toward the “Right” TIRADS. J. Clin. Endocrinol. Metab. 104, 95–102 (2019)

    Article  PubMed  Google Scholar 

  59. X. Chen, Q. Zhou, F. Wang, F. Zhang, H. Du et al. Value of BRAF V600E in high-risk thyroid nodules with benign cytology results. AJNR Am. J. Neuroradiol. 39, 2360–2365 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are grateful to Dr. Katia Cioni and Prof. Cesare Carani (Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena & Reggio Emilia, Modena ItalyUnit of Endocrinology, Department of Medical Specialties, Azienza Ospedaliero-Universitaria of Modena, Ospedale Civile of Baggiovara, Modena, Italy) for their contribution in the realization of the MoCyThy database.

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by S.D.V. and V.R. The first draft of the manuscript was written by S.D.V., G.B., and V.R. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Correspondence to Vincenzo Rochira.

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In view of the retrospective nature of the study, Informed Consent was waived by the Institutional Review Board of Azienda USL Modena.

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The present study was approved by the Institutional Review Board of Azienda USL Modena on October 28, 2013.

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De Vincentis, S., Brigante, G., Ansaloni, A. et al. Value of repeated US-guided fine-needle aspiration (US-FNAB) in the follow-up of benign thyroid nodules: a real-life study based on the MoCyThy (Modena’s Cytology of the Thyroid) DATABASE with a revision of the literature. Endocrine 84, 193–202 (2024). https://doi.org/10.1007/s12020-023-03641-y

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