Similar articles

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-to-peak 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.

甲状腺不确定结节的回顾性细胞学评估研究

[1]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.

[2]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.

[3]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.

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

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

[6]Castro, M.R., Gharib, H., 2003. Thyroid fine-needle aspiration biopsy: progress, practice and pitfalls. Endocr. Pract., 9(2):128-136.

[7]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.

[8]Cibas, E.S., Ali, S.Z., 2009. The Bethesda System for Reporting Thyroid Cytopathology. Thyroid, 19(11):1159-1165.

[9]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.

[10]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.

[11]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.

[12]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.

[13]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.

[14]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.

[15]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.

[16]Giusti, M., Orlandi, D., Melle, G., et al., 2013. Is there a real diagnostic impact of elastosonography and contrast-enhanced ultrasonography in the management of thyroid nodules? J. Zejiang Univ.-Sci. B (Biomed. & Biotechnol.), 14(3):195-206.

[17]Giusti, M., Campomenosi, C., Gay, S., et al., 2014. The use of semi-quantitative ultrasound elastosonography in combination with conventional ultrasonography and contrast-enhanced ultrasonography in the assessment of malignancy risk of thyroid nodules with indeterminate cytology. Thyroid Res., 7(1):9.

[18]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.

[19]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.

[20]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.

[21]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.

[22]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.

[23]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.

[24]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.

[25]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.

[26]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.

[27]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.

[28]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.

[29]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.

[30]Mehta, R.S., Carty, S.E., Ohori, N.P., et al., 2013. Nodular size is an independent predictor of malignancy in mutation-negative nodules with follicular lesion of undetermined significance cytology. Surgery, 154(4):730-738.

[31]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.

[32]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.

[33]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.

[34]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.

[35]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.

[36]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.

[37]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.

[38]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.

[39]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.

[40]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.

[41]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.

[42]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.

[43]Yeh, M.W., Demircan, O., Ituarte, P., et al., 2004. False-negative fine needle aspiration cytology results delay treatment and adversely affect outcome in patients with thyroid carcinoma. Thyroid, 14(3):207-215.

[44]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.

[45]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.