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Retrospective cytological evaluation of indeterminate thyroid nodules according to the British Thyroid Association 2014 classification and comparison of clinical evaluation and outcomes

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Abstract

The cytology of 130 indeterminate nodules (Thy 3) was retrospectively reviewed according to the British Thyroid Association 2014 classification. Nodules were divided into Thy 3a (atypical features) and Thy 3f (follicular lesion) categories. Histology was available as a reference for 97 nodules. Pre-surgical evaluations comprised biochemical tests, color-Doppler ultrasonography (US), semi-quantitative elastography-US (USE), contrast-enhanced US (CEUS), and mutation analysis from cytological slides. Thyroid malignancy was the final diagnosis for 19% of surgically-treated nodules. No statistically significant difference in the risk of malignancy was found between Thy 3a (26%) and Thy 3f (14%) nodules. Histology of the Thy 3a and Thy 3f nodules showed a higher incidence of Hurtle cell adenomas in Thy 3f (29%) than in Thy 3a (3%) nodules (P=0.01). The only pre-surgical difference concerned the BRAF V600E mutation, which was positive in some Thy 3a but not in any Thy 3f nodules (P=0.04). Receiver-operating characteristic (ROC) analysis was used to obtain cut-off values from US (score), USE (ELX 2/1 strain index), and CEUS (time-topeak index and peak index) data. The cut-off values were similar for Thy 3a and Thy 3f nodules. Data showed that malignancy can be suspected if the US score is >2, ELX 1/2 strain index >1, time-to-peak index >1, and peak index <1. In a sub-group of 24 revised nodules (12 Thy 3a and 12 Thy 3f) with histology as a reference, the diagnostic power of cumulative pre-surgical analysis by means of US, USE, and CEUS showed high positive and negative predictive values (83% and 100%, respectively) for the presence of malignancy in Thy 3a and Thy 3f nodules. In conclusion, in our series of revised Thy 3 nodules, malignancy was low and displayed no significant differences between Thy 3a and Thy 3f categories. The use of cut-offs based on histology as a reference could reduce surgery. Our data support the conviction that, in mutation-negative Thy 3a and Thy 3f nodules, observation should be the first choice when not all instrumental results are suspect.

中文概要

题目

甲状腺不确定结节的回顾性细胞学评估研究

目的

回顾性分析了130 例甲状腺不确定结节的临床评估和预后,以及组织细胞学检测结果,为甲状腺结节的治疗提供合理的治疗方法。

方法

根据英国甲状腺协会2014 年分类,回顾性分析了2011 年1 月至2014 年12 月130 例甲状腺不确定结节(Thy 3)的细胞学检查。将结节分为Thy 3a(非典型特征)和Thy 3f(滤泡病变)两类。比较评估术前生物化学检查、彩色多普勒超声检查(US)、半定量弹性超声成像(USE)、超声造影(CEUS)、细胞学、组织学以及分子生物学突变分析等结果。

结论

Thy 3 结节的恶性肿瘤发生率较低,且在Thy 3a和Thy 3f 之间没有显著差异。使用基于组织学的截取值作为参考可以降低采用手术的治疗方案。在阴性突变的Thy 3a 和Thy 3f 结节中,当不是所有的仪器检测结果都疑是阳性时,组织学观察应该作为首选。

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References

  • Alexander, E.K., Heering, J.P., Benson, C.B., et al., 2002. Assessment of nondiagnostic ultrasound-guided fine needle aspiration of thyroid nodules. J. Clin. Endocrinol. Metab., 87(11): 4924–4927. http://dx.doi.org/10.1210/jc.2002-020865

    Article  CAS  PubMed  Google Scholar 

  • Azizi, G., Keller, J.M., Mayo, M.L., et al., 2015. Thyroid nodules and shear wave elastography: a new tool in thyroid cancer detection. Ultrasound Med. Biol., 41(11): 2855–2865. http://dx.doi.org/10.1016/j.ultrasmedbio.2015.06.021

    Article  PubMed  Google Scholar 

  • Bongiovanni, M., Spitale, A., Faquin, W.C., et al., 2012. The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol., 56(4): 333–339. http://dx.doi.org/10.1159/000339959

    Article  PubMed  Google Scholar 

  • BTA (British Thyroid Association), 2007. Guidelines for the Management of Thyroid Cancer in Adults. Royal College of Physicians, London.

  • BTA (British Thyroid Association), 2014. Guidelines for the Management of Thyroid Cancer. Royal College of Physicians, London.

  • Castro, M.R., Gharib, H., 2003. Thyroid fine-needle aspiration biopsy: progress, practice and pitfalls. Endocr. Pract., 9(2): 128–136. http://dx.doi.org/10.4158/EP.9.2.128

    Article  PubMed  Google Scholar 

  • Choi, Y.J., Baek, J.H., Ha, E.J., et al., 2014. Differences in risk of malignancy and management recommendations in subcategories of thyroid nodules with atypia of undetermined significance or follicular lesion of undetermined significance: the role of ultrasound-guided core-needle biopsy. Thyroid, 24(3): 494–501. http://dx.doi.org/10.1089/thy.2012.0635

    Article  PubMed  Google Scholar 

  • Cibas, E.S., Ali, S.Z., 2009. The Bethesda System for Reporting Thyroid Cytopathology. Thyroid, 19(11): 1159–1165. http://dx.doi.org/10.1089/thy.2009.0274

    Article  PubMed  Google Scholar 

  • Cooper, D.S., Doherty, G.M., Haugen, B.R., et al., 2009. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid, 19(11): 1167–1214. http://dx.doi.org/10.1089/thy.2009.0110

    Article  PubMed  Google Scholar 

  • Cuhaci, N., Arpaci, D., Ucler, R., et al., 2014. Malignancy rate of thyroid nodules defined as follicular lesion of undetermined significance and atypia of undetermined significance in thyroid cytopathology and its relation with ultrasonographic features. Endocr. Pathol., 25(3): 248–256. http://dx.doi.org/10.1007/s12022-014-9298-7

    Article  PubMed  Google Scholar 

  • Deandrea, M., Ragazzoni, F., Motta, M., et al., 2010. Diagnostic value of a cytomorphological subclassification of follicular patterned thyroid lesions: a study of 927 consecutive cases with histological correlation. Thyroid, 20(10): 1077–1083. http://dx.doi.org/10.1089/thy.2010.0015

    Article  PubMed  Google Scholar 

  • de Lellis, R.A., Willimas, E.D., 2004. Thyroid and parathyroid tumors. In: de Lellis, R.A., Lloyd, R., Heitz, P.U., et al. (Eds.), World Health Organization Classification of Tumours. Pathology & Genetics of Tumours of Endocrine Organs. JARC Press, Lyon, p.49–97.

    Google Scholar 

  • Deniwar, A., Hambleton, C., Thethi, T., et al., 2015. Examining the Bethesda criteria risk stratification of thyroid nodules. Pathol. Res. Pract., 211(5): 345–348. http://dx.doi.org/10.1016/j.prp.2015.02.005

    Article  PubMed  Google Scholar 

  • Dincer, N., Balci, S., Yazgan, A., et al., 2013. Follow-up of atypia and follicular lesions of undetermined significance in thyroid fine needle aspiration cytology. Cytopathology, 24(6): 385–390. http://dx.doi.org/10.1111/cyt.12021

    Article  CAS  PubMed  Google Scholar 

  • Eszlinger, M., Krogdahl, A., Munz, S., et al., 2014. Impact of molecular screening for point mutation and rearrangements in routine air-dried fine-needle aspiration samples of thyroid nodules. Thyroid, 24(2): 305–313. http://dx.doi.org/10.1089/thy.2013.0278

    Article  CAS  PubMed  Google Scholar 

  • Giusti, M., Orlandi, D., Melle, G., et al., 2013. Is there a real diagnostic impact of elastosonography and contrastenhanced ultrasonography in the management of thyroid nodules? J. Zejiang Univ.-Sci. B (Biomed. & Biotechnol.), 14(3): 195–206. http://dx.doi.org/10.1631/jzus.B1200106

    Article  Google Scholar 

  • Giusti, M., Campomenosi, C., Gay, S., et al., 2014. The use of semi-quantitative ultrasound elastosonography in combination with conventional ultrasonography and contrastenhanced ultrasonography in the assessment of malignancy risk of thyroid nodules with indeterminate cytology. Thyroid Res., 7(1):9. http://dx.doi.org/10.1186/s13044-014-0009-8

    Article  PubMed  PubMed Central  Google Scholar 

  • Haugen, B.R., Alexander, E.K., Bible, K.C., et al., 2016. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid, 26(1): 1–133. http://dx.doi.org/10.1089/thy.2015.0020

    Article  PubMed  PubMed Central  Google Scholar 

  • Ho, A.S., Sarti, E.E., Jain, K.S., et al., 2014. Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS). Thyroid, 24(5): 832–839. http://dx.doi.org/10.1089/thy.2013.0317

    Article  PubMed  PubMed Central  Google Scholar 

  • Horvath, E., Majlis, S., Rossi, R., et al., 2009. An ultrasonogram reporting system for thyroid nodules stratifying cancer risk for clinical management. J. Clin. Endocrinol. Metab., 94(5): 1748–1751. http://dx.doi.org/10.1210/jc.2008-1724

    Article  CAS  PubMed  Google Scholar 

  • Hyeon, J., Ahn, S., Shin, J.H., et al., 2014. The prediction of malignant risk in the category “atypia of undetermined significance/follicular lesion of undetermined significance” of the Bethesda System for Reporting Thyroid Cytopathology using subcategorization and BRAF mutation results. Cancer Cytopathol., 122(5): 368–376. http://dx.doi.org/10.1002/cncy.21396

    Article  CAS  PubMed  Google Scholar 

  • Jo, V.Y., Stelowm, E.B., Dustin, S.M., et al., 2010. Malignancy risk for fine-needle aspiration of thyroid according to the Bethesda System for Reporting Thyroid Cytopathology. Am. J. Clin. Pathol., 134(3): 450–456. http://dx.doi.org/10.1309/AJCP5N4MTHPAFXFB

    Article  PubMed  Google Scholar 

  • Kakudo, K., Kameyama, K., Miyauchi, A., et al., 2014. Introducing the reporting system for thyroid fine-needle aspiration cytology according to the new guidelines of the Japan Thyroid Association. Endocr. J., 61(6): 539–552. http://dx.doi.org/10.1507/endocrj.EJ13-0494

    Article  PubMed  Google Scholar 

  • Kakudo, K., Kameyama, K., Hirokawa, M., et al., 2015. Subclassfication of follicular neoplasms recommended by the Japan Thyroid Association reporting system of thyroid cytology. Int. J. Endocrinol., 2015:938305. http://dx.doi.org/10.1155/2015/938305

    Article  PubMed  PubMed Central  Google Scholar 

  • Kapila, K., Qadan, L., Ali, R.H., et al., 2015. The Bethesda System for Reporting Thyroid fine-needle aspiration cytology: a Kuwaiti experience—a cytohistopathological study of 374 cases. Acta Cytol., 59(2): 133–138. http://dx.doi.org/10.1159/000371538

    Article  CAS  PubMed  Google Scholar 

  • Kim, S.Y., Han, K.H., Moon, H.J., et al., 2014. Thyroid nodules with benign findings at cytology: results of long term follow-up with US. Radiology, 271(1): 272–281. http://dx.doi.org/10.1148/radiol.13131334

    Article  PubMed  Google Scholar 

  • Kocjan, G., Chandra, A., Cross, P.A., et al., 2011. The interobserver reproducibility of thyroid fine-needle aspiration using the UK Royal College of Pathologists’ Classification System. Am. J. Clin. Pathol., 135(6): 852–859. http://dx.doi.org/10.1309/AJCPZ33MVMGZKEWU

    Article  PubMed  Google Scholar 

  • Labourier, E., Shifrin, A., Busseniers, A.E., et al., 2015. Molecular testing for miRNA, and DNA on fine-needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology. J. Clin. Endocrinol. Metab., 100(7): 2743–2750. http://dx.doi.org/10.1210/jc.2015-1158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCoy, K.L., Jabbour, N., Ogilvie, J.B., et al., 2007. The incidence of cancer and rate of false-negative cytology in thyroid nodules greater than or equal to 4 cm in size. Surgery, 142(6): 837–844. http://dx.doi.org/10.1016/j.surg.2007.08.012

    Article  PubMed  Google Scholar 

  • Mehta, R.S., Carty, S.E., Ohori, N.P., et al., 2013. Nodular size is an independent predictor of malignancy in mutationnegative nodules with follicular lesion of undetermined significance cytology. Surgery, 154(4): 730–738. http://dx.doi.org/10.1016/j.surg.2013.05.015

    Article  PubMed  Google Scholar 

  • Mihai, R., Parker, A.J., Roskell, D., et al., 2009. One in four patients with follicular thyroid cytology (THY 3) has a thyroid carcinoma. Thyroid, 19(1): 33–37. http://dx.doi.org/10.1089/thy.2008.0200

    Article  PubMed  Google Scholar 

  • Monti, E., Bovero, M., Mortara, L., et al., 2015. BRAF mutation in an Italian regional population: implications for the therapy of thyroid cancer. Int. J. Endocrinol., 2015:138734. http://dx.doi.org/10.1155/2015/138734

    Article  PubMed  PubMed Central  Google Scholar 

  • Moon, H.J., Kim, E.K., Yonn, J.H., et al., 2015. Malignancy risk stratification in thyroid nodules with nondiagnostic results at cytologic examination: combination of thyroid imaging and data system and the Bethesda system. Radiology, 274(1): 287–295. http://dx.doi.org/10.1148/radiol.14140359

    Article  PubMed  Google Scholar 

  • Moon, W.J., Baek, J.H., Jung, S.L., et al., 2011. Ultrasonography and the ultrasound-based management of thyroid nodules: consensus statement and recommendations.

  • Korean J. Radiol., 12(1): 1–14. http://dx.doi.org/10.3348/kjr.2011.12.1.1

  • Nakamura, H., Hirokawa, M., Ota, H., et al., 2015. Is an increase in thyroid nodule volume a risk factor for malignancy? Thyroid, 25(7): 804–811. http://dx.doi.org/10.1089/thy.2014.0567

  • Nikiforov, Y.E., Carty, S.E., Chiosea, S.I., et al., 2014. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer, 120(23): 3627–3634. http://dx.doi.org/10.1002/cncr.29038

    Article  CAS  PubMed  Google Scholar 

  • Nou, E., Kwong, N., Alexander, L.K., et al., 2014. Determination of optimal time interval for repeat evaluation following a benign thyroid nodule aspiration. J. Clin. Endocorinol. Metab., 99(2): 510–516. http://dx.doi.org/10.1210/jc.2013-3160

    Article  CAS  Google Scholar 

  • Ohori, N.P., Wolfe, J., Hodak, S.P., et al., 2013. “Colloid-rich” follicular neoplasm/suspicious for follicular neoplasm thyroid fine-needle aspiration specimens: cytologic, histologic, and molecular basis for considering an alternate view. Cancer Cytopathol., 121(12): 718–728. http://dx.doi.org/10.1002/cncy.21333

    Article  PubMed  Google Scholar 

  • Rago, T., Scutari, M., Latrofa, F., et al., 2014. The large majority of 1520 patients with indeterminate thyroid nodule at cytology have a favorable outcome and a clinical risk score has a high negative predictive value for more cumbersome cancer disease. J. Clin. Endocrinol. Metab., 99(10): 3700–3707. http://dx.doi.org/10.1210/jc.2013-4401

    Article  CAS  PubMed  Google Scholar 

  • Rosario, P.W., 2014. Thyroid nodules with atypia or follicular lesions of undetermined significance (Bethesda category III): importance of ultrasonography and cytological subcategory. Thyroid, 24(7): 1115–1120. http://dx.doi.org/10.1089/thy.2013.0650

    Article  PubMed  Google Scholar 

  • Trimboli, P., Bongiovanni, M., Rossi, F., et al., 2015. Differentiated thyroid cancer patients with previous indeterminate (Thy 3) cytology have a better prognosis than those with suspicious or malignant FNAC reports. Endocrine, 49(1): 191–195. http://dx.doi.org/10.1007/s12020-014-0453-1

    Article  CAS  PubMed  Google Scholar 

  • Wharry, L.I., McCoy, K.L., Stang, M.T., et al., 2014. Thyroid nodules (>4 cm): can ultrasound and cytology reliably exclude cancer? World J. Surg., 38(3): 614–621. http://dx.doi.org/10.1007/s00268-013-2261-9

    Google Scholar 

  • Yeh, M.W., Demircan, O., Ituarte, P., et al., 2004. Falsenegative fine needle aspiration cytology results delay treatment and adversely affect outcome in patients with thyroid carcinoma. Thyroid, 14(3): 207–215. http://dx.doi.org/10.1089/105072504773297885

    Article  PubMed  Google Scholar 

  • Yoo, M.R., Gweon, H.M., Parkm, A.Y., et al., 2015. Repeat diagnoses of Bethesda category III thyroid nodules: what to do next? PLoS ONE, 10(6): e0130138. http://dx.doi.org/10.1371/journal.pone.0130138

  • Yoon, J.H., Lee, H.S., Kim, E.K., et al., 2014. A nomogram for predicting malignancy in thyroid nodules diagnosed as atypia of undetermined significance/follicular lesions if undetermined significance on fine needle aspiration. Surgery, 155(6): 1006–1013. http://dx.doi.org/10.1016/j.surg.2013.12.035

    Article  PubMed  Google Scholar 

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Correspondence to Massimo Giusti.

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ORCID: Massimo GIUSTI, http://orcid.org/0000-0002-1269-8376

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Giusti, M., Massa, B., Balestra, M. et al. Retrospective cytological evaluation of indeterminate thyroid nodules according to the British Thyroid Association 2014 classification and comparison of clinical evaluation and outcomes. J. Zhejiang Univ. Sci. B 18, 555–566 (2017). https://doi.org/10.1631/jzus.B1600075

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