Skip to main content

Advertisement

SpringerLink
Log in

Malignancy is associated with microcalcification and higher AP/T ratio in ultrasonography, but not with Hashimoto’s thyroiditis in histopathology in patients with thyroid nodules evaluated as Bethesda Category III (AUS/FLUS) in cytology

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

Abstract

The predictors of malignancy are important for the decision of appropriate management in nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). Our aim was to determine the ultrasonographical, clinical, and biochemical predictors of malignancy in these patients. A total of 427 patients with cytologically Bethesda Category III (AUS/FLUS) thyroid nodules were included in this retrospective study. We divided the nodules into two subgroups according to the histopathology as benign and malignant, and compared the preoperative ultrasonographical, clinical, and biochemical findings. In overall, 427 patients with 449 AUS/FLUS nodules who had undergone surgery, the rate of malignancy was 23.4 % (105/449). When evaluated separately, the rate of malignancy was 25.8 % in nodules with AUS (82/318) and 17.6 % in nodules with FLUS (23/131) (p = 0.061). The vast majority of malignant specimens in histopathology consisted of papillary thyroid carcinoma (PTC) (n = 91, 86.7 %). Preoperative ultrasonographic features of 105 malignant nodules in histopathology were compared with the 344 benign nodules in histopathology. Anteroposterior/Transverse (AP/T) ratio was significantly higher in malignant group compared to benign group (p = 0.013). In multiple logistic analysis, we found that higher AP/T ratio and microcalcification were independently associated with malignancy (p < 0.05). The malignancy-associated cut-off value of AP/T ratio at maximum sensitivity and specificity was ≥0.81. We did not find any correlation between malignancy and Hashimoto’s thyroiditis in histopathology in multivariate analysis (p > 0.05). In Bethesda Category III nodules with higher AP/T ratio and microcalcification, surgery might be considered as a first therapeutic option instead of repeat fine-needle aspiration biopsy or observation.

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
Fig. 2

Similar content being viewed by others

References

  1. H. Gharib, J.R. Goellner, D.A. Johnson, Fine-needle aspiration cytology of the thyroid: a 12 year experience with 11,000 biopsies. Clin. Lab. Med. 13, 699–709 (1993)

    CAS  PubMed  Google Scholar 

  2. H. Gharib, J.R. Goellner, Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann. Intern. Med. 118, 282–289 (1993)

    Article  CAS  PubMed  Google Scholar 

  3. 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 

  4. S.Z. Ali, E.S. Cibas, The Bethesda system for reporting thyroid cytopathology (Springer, New York, 2010)

    Book  Google Scholar 

  5. M. Bongiovanni, J.F. Krane, E.S. Cibas, W.C. Faquin, The atypical thyroid fine-needle aspiration: past, present, and future. Cancer. Cytopathol. 120, 73–86 (2012)

    Article  PubMed  Google Scholar 

  6. E.S. Cibas, S.Z. Ali, The Bethesda system for reporting thyroid cytopathology. Thyroid. 19, 1159–1165 (2009)

    Article  PubMed  Google Scholar 

  7. A.S. Ho, E.E. Sarti, K.S. Jain, H. Wang, I.J. Nixon, A.R. Shaha, J.P. Shah, D.H. Kraus, R. Ghossein, S.A. Fish, R.J. Wong, O. Lin, L.G. Morris, Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS). Thyroid. 24, 832–839 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  8. P.W. Rosario, Thyroid nodules with atypia or follicular lesions of undetermined significance (Bethesda Category III): importance of ultrasonography and cytological subcategory. Thyroid. 24, 1115–1120 (2014)

    Article  PubMed  Google Scholar 

  9. K.H. Lee, J.H. Shin, Y.L. Oh, S.Y. Hahn, Aytpia of undetermined significance in thyroid fine-needle aspiration cytology: prediction of malignancy by US and comparison of methods for further management. Ann. Surg. Oncol. 21, 2326–2331 (2014)

    Article  PubMed  Google Scholar 

  10. N. Çuhaci, D. Arpaci, R. Üçler, A.K. Yazgan, G. Kıyak, S. Yalçin, P.E. Ersoy, G. Güler, R. Ersoy, B. Çakir, Malignancy rate of thyroid nodules defined as follicular lesion of undetermined significance and atypia of undetermined significance in thyroid pathology and its relation with ultrasonographic features. Endocr. Pathol. 25, 248–256 (2014)

    Article  PubMed  Google Scholar 

  11. N.P. Ohori, K.E. Schoedel, Variability in the atypia of undetermined significance/follicular lesion of undetermined significance diagnosis in the Bethesda system for reporting thyroid cytopathology: sources and recommendations. Acta. Cytol. 55, 492–498 (2011)

    Article  PubMed  Google Scholar 

  12. 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 

  13. R.S. Mehta, S.E. Carty, N.P. Ohori, S.P. Hodak, C. Coyne, S.O. LeBeau, M.E. Tublin, M.T. Stang, J.T. Johnson, K.L. McCoy, M.N. Nikiforova, Y.E. Nikiforov, L. Yip, Nodule size is an independent predictor of malignancy in mutation-negative nodules with follicular lesion of undetermined significance cytology. Surgery. 154, 730–736 (2013)

    Article  PubMed  Google Scholar 

  14. E.K. Alexander, G.C. Kennedy, Z.W. Baloch, E.S. Cibas, D. Chudova, J. Diggans, L. Friedman, R.T. Kloos, V.A. LiVolsi, S.J. Mandel, S.S. Raab, J. Rosai, D.L. Steward, P.S. Walsh, J.I. Wilde, M.A. Zeiger, R.B. Lanman, B.R. Haugen, Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N. Engl. J. Med. 367, 705–715 (2012)

    Article  CAS  PubMed  Google Scholar 

  15. D. Vriens, J.H. de Wilt, G.J. van der Wilt, R.T. Netea-Maier, W.J. Oyen, L.F. de Geus-Oei, The role of [18F]-2-fluoro-2-deoxy-d-glucose-positron emission tomography in thyroid nodules with indeterminate fine-needle aspiration biopsy: systematic review and meta-analysis of the literature. Cancer. 117, 4582–4594 (2011)

    Article  PubMed  Google Scholar 

  16. V. Cantisani, P. Maceroni, V. D’Andrea, G. Patrizi, M. Di Segni, C. De Vito, H. Grazhdani, A.M. Isidori, E. Giannetta, A. Redler, F. Frattaroli, L. Giacomelli, G. Di Rocco, C. Catalano, F. D’Ambrosio, Strain ratio ultrasound elastography increases the accuracy of colour-Doppler ultrasound in the evaluation of Thy-3 nodules. A bi-centre university experience. Eur. Radiol. (2015). doi:10.1007/s00330-015-3956-0

    Google Scholar 

  17. N. Hayashi, N. Tamaki, J. Konishi, Y. Yonekura, M. Senda, K. Kasagi, K. Yamamoto, Y. Iida, T. Misaki, K. Endo, K. Torizuka, T. Mori, Sonography of Hashimoto thyroiditis. J. Clin. Ultrasound 14, 123–126 (1986)

    Article  CAS  PubMed  Google Scholar 

  18. R. Gutekunst, W. Hafermann, T. Mansky, P.C. Scriba, Ultrasonography related to clinical and laboratory findings in lymphocytic thyroiditis. Acta. Endocrinol. (Copenh). 121, 129–135 (1989)

    CAS  PubMed  Google Scholar 

  19. M.E. Dailey, S. Lindsay, R. Skahen, Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. AMA. Arch. Surg. 70, 291–297 (1955)

    Article  CAS  PubMed  Google Scholar 

  20. R.N. Hirabayashi, S. Lindsay, The relation of thyroid carcinoma and chronic thyroiditis. Surg. Gynecol. Obstet. 121, 243–252 (1965)

    CAS  PubMed  Google Scholar 

  21. D.R. Maceri, M.J. Sullivan, K.D. McClatchney, Autoimmune thyroiditis: pathophysiology and relationship to thyroid cancer. Laryngoscope. 96, 82–86 (1986)

    Article  CAS  PubMed  Google Scholar 

  22. C. Cipolla, L. Sandonato, G. Graceffa, S. Fricano, A. Torcivia, S. Vieni, S. Latteri, M.A. Latteri, Hashimoto thyroiditis coexistent with papillary thyroid carcinoma. Am. Surg. 71, 874–878 (2005)

    PubMed  Google Scholar 

  23. M.L. Shih, J.A. Lee, C.B. Hsieh, J.C. Yu, H.D. Liu, E. Kebebew, O.H. Clark, Q.Y. Duh, Thyroidectomy for Hashimoto’s thyroiditis: complications and associated cancers. Thyroid. 18, 729–734 (2008)

    Article  PubMed  Google Scholar 

  24. C. Anil, S. Goksel, A. Gursoy, Hashimoto’s thyroiditis is not associated with increased risk of thyroid cancer in patients with thyroid nodules: a single-center prospective study. Thyroid. 20, 601–606 (2010)

    Article  PubMed  Google Scholar 

  25. K. Gul, A. Dirikoc, G. Kiyak, P.E. Ersoy, N.S. Ugras, R. Ersoy, B. Cakir, The association between thyroid carcinoma and Hashimoto’s thyroiditis: the ultrasonographic and histopathologic characteristics of malignant nodules. Thyroid. 20, 873–878 (2009)

    Article  Google Scholar 

  26. B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov, F. Pacini, G.W. Randolph, A.M. Sawka, M. Schlumberger, K. Schuff, S.I. Sherman, J.A. Sosa, D.L. Steward, R.M. Tuttle, L. Wartofsky, American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. (2015). doi:10.1089/thy.2015.0020

    Google Scholar 

  27. I. Kholova, M. Ludvıkova, Thyroid atypia of undetermined significance or follicular lesion of undetermined significance: an indispensable Bethesda 2010 diagnostic category or waste carbage? Acta. Cytol. 58, 319–329 (2014)

    Article  PubMed  Google Scholar 

  28. J.Y. Park, H.J. Lee, H.W. Jang, H.K. Kim, J.H. Yi, W. Lee, S.H. Kim, A proposal for a thyroid imaging reporting and data system for ultrasound features of thyroid carcinoma. Thyroid. 19, 1257–1264 (2009)

    Article  PubMed  Google Scholar 

  29. J.Y. Kwak, K.H. Han, J.H. Yoon, H.J. Moon, E.J. Son, S.H. Park, H.K. Jung, J.S. Choi, B.M. Kim, E.K. Kim, Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology. 260, 892–899 (2011)

    Article  PubMed  Google Scholar 

  30. H.M. Gweon, E.J. Son, J.H. Youk, J.A. Kim, Thyroid nodules with Bethesda system III cytology: Can ultrasonography guide the next step? Ann. Surg. Oncol. 20, 3083–3088 (2013)

    Article  PubMed  Google Scholar 

  31. W.S. Yoo, H.S. Choi, S.W. Cho, J.H. Moon, K.W. Kim, H.J. Park, S.Y. Park, S.I. Choi, S.H. Choi, S. Lim, K.H. Yi, J. do Park, H.C. Jang, Y.J. Park, The role of ultrasound findings in the management of thyroid nodules with atypia or follicular lesions of undetermined significance. Clin. Endocrinol. (Oxf). 80, 735–742 (2014)

    Article  PubMed  Google Scholar 

  32. R. Carr, B. Ustun, D. Chhieng, K. Schofield, C. Theoharis, L. Hammers, A.J. Adeniran, Radiologic and clinical predictors of malignancy in the follicular lesion of undetermined significance of the thyroid. Endocr. Pathol. 24, 62–68 (2013)

    Article  PubMed  Google Scholar 

  33. S.W. Lee, H.J. Lee, H.J. Kim, J. Lee, J.Y. Park, S.H. Kim, J. Kim, Combined categorical reporting systems of US and cytology findings for thyroid nodules: guidance on repeat fine-needle aspiration cytology. Radiology. 266, 956–963 (2013)

    Article  PubMed  Google Scholar 

  34. 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 

  35. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice Guidelines in Oncology: Thyroid Carcinoma version2. NCCN, Fort Washington, PA. Available at: www.nccn.org (2013)

  36. P.W. Rosario, L.S. Ward, G.A. Carvalho, H. Graf, R.M. Maciel, L.M. Maciel, A.L. Maia, M. Vaisman, Thyroid nodules and differentiated thyroid cancer: Update on the Brazilian consensus. Arq. Bras. Endocrinol. Metabol. 57, 240–264 (2013)

    Article  PubMed  Google Scholar 

  37. Y.J. Choi, J.H. Baek, E.J. Ha, H.K. Lim, J.H. Lee, J.K. Kim, D.E. Song, Y.K. Shong, S.J. Hong, Different risk of malignancy and management recommendations in subcategories of thyroid nodules with atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS): The role of US-guided core-needle biopsy (CNB). Thyroid. 24, 494–501 (2014)

    Article  PubMed  Google Scholar 

  38. D.G. Na, J.H. Kim, J.Y. Sung, J.H. Baek, K.C. Jung, H. Lee, H. Yoo, Core- needle biopsy is more useful than repeat fine-needle aspiration in thyroid nodules read as nondiagnostic or atypia of undetermined significance by the Bethesda System for reporting thyroid cytopathology. Thyroid. 22, 468–475 (2012)

    Article  PubMed  Google Scholar 

  39. 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 

  40. M.T. Olson, D.P. Clark, Y.S. Erozan, S.Z. Ali, Spectrum of risk of malignancy in subcategories of atypia of undetermined significance. Acta. Cytol. 55, 518–525 (2011)

    Article  PubMed  Google Scholar 

  41. K.T. Park, S.H. Ahn, J.H. Mo, Y.J. Park, J. do Park, S.I. Choi, S.Y. Park, Role of core needle biopsy and ultrasonographic finding in the management of indeterminate thyroid nodules. Head Neck 33, 160–165 (2011)

    Article  PubMed  Google Scholar 

  42. S.S. Nagarkatti, W.C. Faquin, C.C. Lubitz, D.M. Garcia, G. Barbesino, D.S. Ross, R.A. Hodin, G.H. Daniels, S. Parangi, Management of thyroid nodules with atypical cytology on fine-needle aspiration biopsy. Ann. Surg. Oncol. 20, 60–65 (2013)

    Article  PubMed  Google Scholar 

  43. 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 

  44. P. Trimboli, N. Nasrollah, S. Amendola, F. Rossi, G. Ramacciato, F. Romanelli, P. Aurella, A. Crescenzi, O. Laurenti, E. Condorelli, C. Ventura, S. Valabrega, Should we use ultrasound features associated with papillary thyroid cancer in diagnosing medullary thyroid cancer? Endocr. J. 59, 503–508 (2012)

    Article  PubMed  Google Scholar 

  45. J.Y. Kwak, K.H. Han, J.H. Yoon, H.J. Moon, E.J. Son, S.H. Park, H.K. Jung, J.S. Choi, B.M. Kim, E.K. Kim, Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology. 260, 892–899 (2011)

    Article  PubMed  Google Scholar 

  46. H.J. Moon, J.M. Sung, E.K. Kim, J.H. Yoon, J.H. Youk, J.Y. Kwak, Diagnostic performance of gray-scale US and elastography in solid thyroid nodules. Radiology. 262, 1002–1013 (2012)

    Article  PubMed  Google Scholar 

  47. A. Ozel, S.M. Erturk, A. Ercan, B. Yılmaz, T. Basak, V. Cantisani, M. Basak, Z. Karpat, The diagnostic efficiency of ultrasound in characterization for thyroid nodules: how many criteria are required to predict malignancy? Med. Ultrason. 14, 24–28 (2012)

    PubMed  Google Scholar 

  48. J.H. Yoon, H.J. Kwon, E.K. Kim, H.J. Moon, J.Y. Kwak, Subcategorization of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS): a study applying Thyroid Imaging Reporting and Data System (TIRADS). Clin. Endocrinol. (2016). doi:10.1111/cen.12987

    Google Scholar 

  49. N.D. Banks, J. Kowalski, H.L. Tsai, H. Somervell, R. Tufano, A.P. Dackiw, M.R. Marohn, D.P. Clark, C.B. Umbricht, M.A. Zeiger, A diagnostic predictive model for indeterminate or suspicious thyroid FNA samples. Thyroid. 18, 933–941 (2008)

    Article  CAS  PubMed  Google Scholar 

  50. J. Jonklaas, H. Nsouli-Maktabi, S.J. Soldin, Endogenous thyrotropin and triiodothyronine concentrations in individuals with thyroid cancer. Thyroid. 18, 943–952 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. K. Gul, D. Ozdemir, A. Dirikoc, A. Oguz, D. Tuzun, H. Baser, R. Ersoy, B. Cakir, Are endogenously lower serum thyroid hormones new predictors for thyroid malignancy in addition to higher serum thyrotropin? Endocrine. 37(2), 253–260 (2010)

    Article  CAS  PubMed  Google Scholar 

  52. E. Fiore, T. Rago, M.A. Provenzale, M. Scutari, C. Ugolini, F. Basolo, G. Di Coscio, P. Berti, L. Grasso, R. Elisei, A. Pinchera, P. Vitti, Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocr. Relat. Cancer 16, 1251–1260 (2009)

    Article  CAS  PubMed  Google Scholar 

  53. J. Zhang, M.A. Lazar, The mechanism of action of thyroid hormones. Annu. Rev. Physiol. 62, 439–466 (2000)

    Article  CAS  PubMed  Google Scholar 

  54. E.L. de Souza Meyer, J.M. Dora, M.S. Wagner, A.L. Maia, Decreased type 1 iodothyronine deiodinase expression might be an early and discrete event in thyroid cell dedifferentation towards papillary carcinoma. Clin. Endocrinol. 62, 672–678 (2005)

    Article  CAS  Google Scholar 

  55. H. Baser, D. Ozdemir, N. Cuhaci, C. Aydin, R. Ersoy, A. Kilicarslan, B. Cakir, Hashimoto’s thyroiditis does not affect ultrasonographical, cytological, and histopathological features in patients with papillary thyroid carcinoma. Endocr. Pathol. 26, 356–364 (2015)

    Article  PubMed  Google Scholar 

  56. J.H. Lee, Y. Kim, J.W. Choi, Y.S. Kim, The association between papillary thyroid carcinoma and histologically proven Hashimoto’s thyroiditis: a meta-analysis. Eur. J. Endocrinol. 168, 343–349 (2013)

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University School of Medicine, Ankara, Turkey

    Oya Topaloglu, Fatma Neslihan Cuhaci, Reyhan Ersoy & Bekir Cakir

  2. Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Ankara, Turkey

    Husniye Baser

  3. Department of Pathology, Ankara Yildirim Beyazit University School of Medicine, Ankara, Turkey

    Nuran Sungu

  4. Department of General Surgery, Ankara Yildirim Beyazit University School of Medicine, Ankara, Turkey

    Abdussamed Yalcin

Authors
  1. Oya Topaloglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Husniye Baser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fatma Neslihan Cuhaci
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nuran Sungu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abdussamed Yalcin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Reyhan Ersoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bekir Cakir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oya Topaloglu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Topaloglu, O., Baser, H., Cuhaci, F.N. et al. Malignancy is associated with microcalcification and higher AP/T ratio in ultrasonography, but not with Hashimoto’s thyroiditis in histopathology in patients with thyroid nodules evaluated as Bethesda Category III (AUS/FLUS) in cytology. Endocrine 54, 156–168 (2016). https://doi.org/10.1007/s12020-016-0982-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-016-0982-x

Keywords

Search

Navigation