Skip to main content
Log in

Diagnostic performance of elastography in cytologically indeterminate thyroid nodules

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

Abstract

Cytological examination of material from fine-needle aspiration biopsy is the mainstay of diagnosis of thyroid nodules, thanks to its remarkable accuracy and scarcity of complications. However, follicular lesions (also called indeterminate lesions or Thy3 in the current classification), a heterogeneous group of lesions in which cytology is unable to give a definitive diagnosis to, represent its main limit. Elastography has been proposed as a potential diagnostic tool to define the risk of malignancy in the aforementioned nodules, but at present there is no conclusive data due to the small number of specifically addressed studies and the lack of concordance among them. The objective of our study was to evaluate the role of real-time elastography (RTE) for refining diagnosis of Thy3 nodules, by integrating diagnostic information provided by traditional ultrasound (US). The study included 108 patients with Thy3 nodules awaiting for surgery, which were evaluated by US (considering hypoecogenicity, irregular margins, microcalcifications, halo sign, and intranodular vascularization) and RTE. Nodules were classified at RTE using a four-class color scale. At histologic examination, 75 nodules were benign and 33 malignant. As expected, none of the ultrasound parameters alone was adequate in predicting malignancy or benignity of the nodules; in the presence of at least two US risk factors, we obtained 61 % sensitivity, 83 % specificity, and 77 % accuracy with 6.8 OR (95 % CI 2.4–20.4). RTE scores 3 and 4 showed 76 % sensitivity, 88 % specificity, 74 % PPV, and 89 % NPV with diagnostic accuracy of 84 %; the data are statistically significant (p < 0.0001) with a OR of 21.9 (95 % CI 7.1–76). By combining RTE with US parameters, the presence of at least 2 characters of suspicion had 88 % sensitivity and 94 % NPV with 23.8 OR (95 % CI 7–106.3). The use of combined RTE and US leads to the identification of two patients subpopulations which have a significantly different malignancy risk (6 vs. 63 %); further studies are needed to verify if it is possible to send only the first group to thyroidectomy and the other to follow-up.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. A.S. Can, K. Peker, Comparison of palpation-versus ultrasound-guided fine-needle aspiration biopsies in the evaluation of thyroid nodules. BMC Res. Notes 1, 12 (2008)

    Article  PubMed Central  PubMed  Google Scholar 

  2. H.H.-J. Wu, J.N. Jones, J. Osman, Fine-needle aspiration cytology of the thyroid: ten years experience in a community teaching hospital. Diagn. Cytopathol. 34, 93–96 (2006)

    Article  PubMed  Google Scholar 

  3. D. Caruso, E. Mazzaferri, Fine needle aspiration biopsy in the management of thyroid nodules. Endocrinologist 1, 194–202 (1991)

    Article  Google Scholar 

  4. M.R. Castro, H. Gharib, Thyroid fine-needle aspiration biopsy: progress, practice, and pitfalls. Endocr. Pract. 9, 128–136 (2003)

    Article  PubMed  Google Scholar 

  5. Z.W. Baloch, S. Fleisher, V.A. LiVolsi, P.K. Gupta, Diagnosis of “follicular neoplasm”: a gray zone in thyroid fine-needle aspiration cytology. Diagn. Cytopathol. 26, 41–44 (2002)

    Article  PubMed  Google Scholar 

  6. R.T. Schlinkert, J.A. van Heerden, J.R. Goellner, H. Gharib, S.L. Smith, R.F. Rosales, A.L. Weaver, Factors that predict malignant thyroid lesions when fine-needle aspiration is “suspicious for follicular neoplasm”. Mayo Clin. Proc. 72, 913–916 (1997)

    Article  CAS  PubMed  Google Scholar 

  7. J.Y. Kwak, E.-K. Kim, H.J. Kim, M.J. Kim, E.J. Son, H.J. Moon, How to combine ultrasound and cytological information in decision making about thyroid nodules. Eur. Radiol. 19, 1923–1931 (2009)

    Article  PubMed  Google Scholar 

  8. P. Trimboli, S. Ulisse, M. D’Alò, F. Solari, A. Fumarola, M. Ruggieri, E. De Antoni, A. Catania, S. Sorrenti, F. Nardi, M. D’Armiento, Analysis of clinical, ultrasound and colour flow-Doppler characteristics in predicting malignancy in follicular thyroid neoplasms. Clin. Endocrinol. (Oxf) 69, 342–344 (2008)

    Article  Google Scholar 

  9. P. Trimboli, G. Treglia, L. Guidobaldi, E. Saggiorato, G. Nigri, A. Crescenzi, F. Romanelli, F. Orlandi, S. Valabrega, R. Sadeghi, L. Giovanella, Clinical characteristics as predictors of malignancy in patients with indeterminate thyroid cytology: a meta-analysis. Endocrine 46, 52–59 (2014)

    Article  CAS  PubMed  Google Scholar 

  10. A. Bartolazzi, F. Orlandi, E. Saggiorato, M. Volante, F. Arecco, R. Rossetto, N. Palestini, E. Ghigo, M. Papotti, G. Bussolati, M.P. Martegani, F. Pantellini, A. Carpi, M.R. Giovagnoli, S. Monti, V. Toscano, S. Sciacchitano, G.M. Pennelli, C. Mian, M.R. Pelizzo, M. Rugge, G. Troncone, L. Palombini, G. Chiappetta, G. Botti, A. Vecchione, R. Bellocco, Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study. Lancet Oncol. 9, 543–549 (2008)

    Article  CAS  PubMed  Google Scholar 

  11. M.R. Sapio, D. Posca, A. Raggioli, A. Guerra, V. Marotta, M. Deandrea, M. Motta, P.P. Limone, G. Troncone, A. Caleo, G. Rossi, G. Fenzi, M. Vitale, Detection of RET/PTC, TRK and BRAF mutations in preoperative diagnosis of thyroid nodules with indeterminate cytological findings. Clin. Endocrinol. (Oxf) 66, 678–683 (2007)

    Article  CAS  Google Scholar 

  12. G. Salvatore, R. Giannini, P. Faviana, A. Caleo, I. Migliaccio, J.A. Fagin, Y.E. Nikiforov, G. Troncone, L. Palombini, F. Basolo, M. Santoro, Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 89, 5175–5180 (2004)

    Article  CAS  PubMed  Google Scholar 

  13. F. Nardi, F. Basolo, A. Crescenzi, G. Fadda, A. Frasoldati, F. Orlandi, L. Palombini, E. Papini, M. Zini, A. Pontecorvi, P. Vitti, Italian consensus for the classification and reporting of thyroid cytology. J. Endocrinol. Invest. 37, 593–599 (2014)

    Article  PubMed  Google Scholar 

  14. Z.W. Baloch, V.A. LiVolsi, S.L. Asa, J. Rosai, M.J. Merino, G. Randolph, P. Vielh, R.M. DeMay, M.K. Sidawy, W.J. Frable, Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn. Cytopathol. 36, 425–437 (2008)

    Article  PubMed  Google Scholar 

  15. E.S. Cibas, S.Z. Ali, The Bethesda system for reporting thyroid cytopathology. Am. J. Clin. Pathol. 132, 658–665 (2009)

    Article  PubMed  Google Scholar 

  16. H. Gharib, E. Papini, R. Paschke, D.S. Duick, R. Valcavi, L. Hegedüs, P. Vitti, 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. Endocr. Pract. 16(Suppl 1), 1–43 (2010)

    Article  PubMed  Google Scholar 

  17. N. Nasrollah, P. Trimboli, L. Guidobaldi, D.D. Cicciarella Modica, C. Ventura, G. Ramacciato, S. Taccogna, F. Romanelli, S. Valabrega, A. Crescenzi, Thin core biopsy should help to discriminate thyroid nodules cytologically classified as indeterminate. A new sampling technique. Endocrine 43, 659–665 (2013)

    Article  CAS  PubMed  Google Scholar 

  18. D. Cosgrove, F. Piscaglia, J. Bamber, J. Bojunga, J.-M. Correas, O.H. Gilja, A.S. Klauser, I. Sporea, F. Calliada, V. Cantisani, M. D’Onofrio, E.E. Drakonaki, M. Fink, M. Friedrich-Rust, J. Fromageau, R.F. Havre, C. Jenssen, R. Ohlinger, A. Săftoiu, F. Schaefer, C.F. Dietrich, EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 2: Clinical applications. Ultraschall Med. 34, 238–253 (2013)

    Article  CAS  PubMed  Google Scholar 

  19. C. Asteria, A. Giovanardi, A. Pizzocaro, L. Cozzaglio, A. Morabito, F. Somalvico, A. Zoppo, US-elastography in the differential diagnosis of benign and malignant thyroid nodules. Thyroid 18, 523–531 (2008)

    Article  PubMed  Google Scholar 

  20. T. Rago, F. Santini, M. Scutari, A. Pinchera, P. Vitti, Elastography: new developments in ultrasound for predicting malignancy in thyroid nodules. J. Clin. Endocrinol. Metab. 92, 2917–2922 (2007)

    Article  CAS  PubMed  Google Scholar 

  21. L. Rubaltelli, S. Corradin, A. Dorigo, M. Stabilito, A. Tregnaghi, S. Borsato, R. Stramare, Differential diagnosis of benign and malignant thyroid nodules at elastosonography. Ultraschall Med. 30, 175–179 (2009)

    Article  CAS  PubMed  Google Scholar 

  22. S. Merino, J. Arrazola, A. Cárdenas, M. Mendoza, P. De Miguel, C. Fernández, T. Ganado, Utility and interobserver agreement of ultrasound elastography in the detection of malignant thyroid nodules in clinical care. AJNR Am. J. Neuroradiol. 32, 2142–2148 (2011)

    Article  CAS  PubMed  Google Scholar 

  23. F. Ragazzoni, M. Deandrea, A. Mormile, M.J. Ramunni, F. Garino, G. Magliona, M. Motta, B. Torchio, R. Garberoglio, P. Limone, High diagnostic accuracy and interobserver reliability of real-time elastography in the evaluation of thyroid nodules. Ultrasound Med. Biol. 38, 1154–1162 (2012)

    Article  PubMed  Google Scholar 

  24. B. Raggiunti, F. Capone, A. Franchi, G. Fiore, S. Filipponi, V. Colagrande, M. Di Nicola, R. Mangifesta, E. Ballone, Ultrasoundelastography: can it provide valid information for differentiation of benign and malignant thyroid nodules? J. Ultrasound 14, 136–141 (2011)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. U. Unlütürk, M.F. Erdoğan, O. Demir, S. Güllü, N. Başkal, Ultrasound elastography is not superior to grayscale ultrasound in predicting malignancy in thyroid nodules. Thyroid 22, 1031–1038 (2012)

    Article  PubMed  Google Scholar 

  26. G. Azizi, J. Keller, M. Lewis Pa, D.W. Puett, K. Rivenbark, C.D. Malchoff, Performance of elastography for the evaluation of thyroid nodules: a prospective study. Thyroid 23, 734–740 (2012)

    Article  Google Scholar 

  27. P. Trimboli, R. Guglielmi, S. Monti, I. Misischi, F. Graziano, N. Nasrollah, S. Amendola, S.N. Morgante, M.G. Deiana, S. Valabrega, V. Toscano, E. Papini, Ultrasound sensitivity for thyroid malignancy is increased by real-time elastography: a prospective multicenter study. J. Clin. Endocrinol. Metab. 97, 4524–4530 (2012)

    Article  CAS  PubMed  Google Scholar 

  28. G. Russ, B. Royer, C. Bigorgne, A. Rouxel, M. Bienvenu-Perrard, L. Leenhardt, Prospective evaluation of thyroid imaging reporting and data system on 4550 nodules with and without elastography. Eur. J. Endocrinol. 168, 649–655 (2013)

    Article  CAS  PubMed  Google Scholar 

  29. J. Bojunga, E. Herrmann, G. Meyer, S. Weber, S. Zeuzem, M. Friedrich-Rust, Real-time elastography for the differentiation of benign and malignant thyroid nodules: a meta-analysis. Thyroid 20, 1145–1150 (2010)

    Article  PubMed  Google Scholar 

  30. M. Andrioli, L. Persani, Elastographic techniques of thyroid gland: current status. Endocrine 46, 455–461 (2014)

    Article  CAS  PubMed  Google Scholar 

  31. P.V. Lippolis, S. Tognini, G. Materazzi, A. Polini, R. Mancini, C.E. Ambrosini, A. Dardano, F. Basolo, M. Seccia, P. Miccoli, F. Monzani, Is elastography actually useful in the presurgical selection of thyroid nodules with indeterminate cytology? J. Clin. Endocrinol. Metab. 96, E1826–E1830 (2011)

    Article  CAS  PubMed  Google Scholar 

  32. M.C. Frates, C.B. Benson, J.W. Charboneau, E.S. Cibas, O.H. Clark, B.G. Coleman, J.J. Cronan, P.M. Doubilet, D.B. Evans, J.R. Goellner, I.D. Hay, B.S. Hertzberg, C.M. Intenzo, R.B. Jeffrey, J.E. Langer, P.R. Larsen, S.J. Mandel, W.D. Middleton, C.C. Reading, S.I. Sherman, F.N. Tessler, Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Radiology 237, 794–800 (2005)

    Article  PubMed  Google Scholar 

  33. F. Tranquart, A. Bleuzen, P. Pierre-Renoult, C. Chabrolle, M. Sam Giao, P. Lecomte, [Elastosonography of thyroid lesions]. J. Radiol. 89, 35–39 (2008)

    Article  CAS  PubMed  Google Scholar 

  34. M. Schlumberger, F. Pacini, Thyroid Tumors (Editions Nucleon, Paris, 2003)

    Google Scholar 

  35. M. Bongiovanni, A. Spitale, W.C. Faquin, L. Mazzucchelli, Z.W. Baloch, The Bethesda system for reporting thyroid cytopathology: a meta-analysis. Acta Cytol. 56, 333–339 (2012)

    Article  PubMed  Google Scholar 

  36. T. Rago, M. Scutari, F. Santini, V. Loiacono, P. Piaggi, G. Di Coscio, F. Basolo, P. Berti, A. Pinchera, P. Vitti, Real-time elastosonography: useful tool for refining the presurgical diagnosis in thyroid nodules with indeterminate or nondiagnostic cytology. J. Clin. Endocrinol. Metab. 95, 5274–5280 (2010)

    Article  CAS  PubMed  Google Scholar 

  37. T. Rago, G. Di Coscio, F. Basolo, M. Scutari, R. Elisei, P. Berti, P. Miccoli, R. Romani, P. Faviana, A. Pinchera, P. Vitti, Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: results from a series of 505 consecutive patients. Clin. Endocrinol. (Oxf) 66, 13–20 (2007)

    CAS  Google Scholar 

  38. H. De Nicola, J. Szejnfeld, A.F. Logullo, A.M.B. Wolosker, L.R.M.F. Souza, V. Chiferi, Flow pattern and vascular resistive index as predictors of malignancy risk in thyroid follicular neoplasms. J. Ultrasound Med. 24, 897–904 (2005)

    PubMed  Google Scholar 

  39. M.C. Frates, C.B. Benson, P.M. Doubilet, E.S. Cibas, E. Marqusee, Can color Doppler sonography aid in the prediction of malignancy of thyroid nodules? J. Ultrasound Med. 22, 127–131 (2003). quiz 132–4

    PubMed  Google Scholar 

  40. M. Andrioli, M. Scacchi, C. Carzaniga, G. Vitale, M. Moro, L. Poggi, L.M. Fatti, F. Cavagnini, Thyroid nodules in acromegaly: the role of elastography. J. Ultrasound 13, 90–97 (2010)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. M. Andrioli, R. Valcavi, The peculiar ultrasonographic and elastographic features of thyroid nodules after treatment with laser or radiofrequency: similarities and differences. Endocrine (2014). doi:10.1007/s12020-014-0241-y

    Google Scholar 

  42. M. Andrioli, L. Persani, Elastographic presentation of synchronous renal cell carcinoma metastasis to the thyroid gland. Endocrine (2013). doi:10.1007/s12020-013-0124-7

    Google Scholar 

  43. M. Andrioli, P. Trimboli, S. Amendola, S. Valabrega, N. Fukunari, M. Mirella, L. Persani, Elastographic presentation of medullary thyroid carcinoma. Endocrine 45, 153–155 (2014)

    Article  CAS  PubMed  Google Scholar 

  44. C. Vorländer, J. Wolff, S. Saalabian, R.H. Lienenlüke, R.A. Wahl, Real-time ultrasound elastography—a noninvasive diagnostic procedure for evaluating dominant thyroid nodules. Langenbecks Arch. Surg. 395, 865–871 (2010)

    Article  PubMed  Google Scholar 

  45. B. Cakir, C. Aydin, B. Korukluoğlu, D. Ozdemir, I.C. Sisman, D. Tüzün, A. Oguz, G. Güler, G. Güney, A. Kuşdemir, S.Y. Sanisoglu, R. Ersoy, Diagnostic value of elastosonographically determined strain index in the differential diagnosis of benign and malignant thyroid nodules. Endocrine 39, 89–98 (2011)

    Article  CAS  PubMed  Google Scholar 

  46. M. Friedrich-Rust, A. Sperber, K. Holzer, J. Diener, F. Grünwald, K. Badenhoop, S. Weber, S. Kriener, E. Herrmann, W.O. Bechstein, S. Zeuzem, J. Bojunga, Real-time elastography and contrast-enhanced ultrasound for the assessment of thyroid nodules. Exp. Clin. Endocrinol. Diabetes 118, 602–609 (2010)

    Article  CAS  PubMed  Google Scholar 

  47. V. Cantisani, H. Grazhdani, P. Ricci, K. Mortele, M. Di Segni, V. D’Andrea, A. Redler, G. Di Rocco, L. Giacomelli, E. Maggini, C. Chiesa, S.M. Erturk, S. Sorrenti, C. Catalano, F. D’Ambrosio, Q-elastosonography of solid thyroid nodules: assessment of diagnostic efficacy and interobserver variability in a large patient cohort. Eur. Radiol. 24, 143–150 (2014)

    Article  PubMed  Google Scholar 

  48. V. Cantisani, S. Ulisse, E. Guaitoli, C. De Vito, R. Caruso, R. Mocini, V. D’Andrea, V. Ascoli, A. Antonaci, C. Catalano, F. Nardi, A. Redler, P. Ricci, E. De Antoni, S. Sorrenti, Q-elastography in the presurgical diagnosis of thyroid nodules with indeterminate cytology. PLoS ONE 7, e50725 (2012)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was partially supported by Compagnia di San Paolo di Torino.

Disclosure

No competing financial interests exist.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Francesca Garino.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garino, F., Deandrea, M., Motta, M. et al. Diagnostic performance of elastography in cytologically indeterminate thyroid nodules. Endocrine 49, 175–183 (2015). https://doi.org/10.1007/s12020-014-0438-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-014-0438-0

Keywords

Navigation