Abstract
Purpose
The classification of indeterminate cytopathology at thyroid fine-needle-aspiration (FNA) has been updated to reduce the number of unnecessary surgery; the 2014 Italian classification introduced the low-risk (TIR3A) and high-risk (TIR3B) subcategories. Aim of this study was to identify the ultrasonographic (US), clinical and cytological predictors of malignancy among TIR3B nodules from a single institution.
Methods
A prospective observational study including 1844 patients who underwent thyroid FNA from June 2014 to January 2019. Ultrasonographic, clinical and cytological features were recorded. All TIR3B diagnoses were referred to surgery. According to final histology, patients were divided into thyroid cancer (TC) or benign nodules. Chi-square test, or Fisher exact test when appropriate, were used to compare groups and logistic regression analyses were used to determine independent predictors of malignancy.
Results
Of 1844 FNAs, 96 (5.2%) were TIR3B. Histology report was available in 65. Among them, 25 (38.5%) were TC. Predictors of TC were nodule size < 20 mm [Odds Ratio (OR) = 5.88, 95% CI 1.91–18.11, p = 0.002], absence or weak intralesional flow [OR = 0.3, 95% CI 0.09–0.77, p = 0.015], microcalcifications [OR = 6.5, 95% CI 1.90–21.93, p = 0.003] at US; nuclear inclusions [OR = 25.3, 95% CI 1.34–476.07, p = 0.031] and chromatin clearing [OR = 3.7, 95% CI 1.27–10.99, p = 0.017] at cytopathology. Patients aged < 55 years had a significantly higher risk of TC [OR = 9.7, 95% CI 2.79–34.07, p < 0.001]. In multivariate analysis, age < 55 and nodule size < 20 mm resulted as independent risk factors.
Conclusions
Patients < 55 years receiving a diagnosis TIR3B on nodules < 20 mm, with microcalcifications, showing specific nuclear atypia at cytopathology are more likely to have TC. Combining US, cytological and clinical features could help determining which patients with a TIR3B diagnosis should be referred to surgery.
Similar content being viewed by others
References
Nardi F, Basolo F, Crescenzi A, Fadda G, Frasoldati A, Orlandi F, Palombini L, Papini E, Zini M, Pontecorvi A, Vitti P (2014) Italian consensus for the classification and reporting of thyroid cytology. J Endocrinol Invest 37(6):593–599. https://doi.org/10.1007/s40618-014-0062-0
Kwak JY, Han KH, Yoon JH, Moon HJ, Son EJ, Park SH, Jung HK, Choi JS, Kim BM, Kim EK (2011) Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology 260(3):892–899. https://doi.org/10.1148/radiol.11110206
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L (2016) 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):1–133. https://doi.org/10.1089/thy.2015.0020
Rullo E, Minelli G, Bosco D, Nardi F, Ascoli V (2018) Evaluation of the Italian cytological subclassification of thyroid indeterminate nodules into TIR-3A and TIR-3B: a retrospective study of 290 cases with histological correlation from a single institution. J Endocrinol Invest 41(5):531–538. https://doi.org/10.1007/s40618-017-0763-2
Trimboli P, Crescenzi A, Giovanella L (2018) Performance of Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) in discriminating indeterminate lesions at low and high risk of malignancy. A systematic review and meta-analysis. Endocrine 60(1):31–35. https://doi.org/10.1007/s12020-017-1382-6
Trimboli P, Crescenzi A, Castellana M, Giorgino F, Giovanella L, Bongiovanni M (2019) Italian consensus for the classification and reporting of thyroid cytology: the risk of malignancy between indeterminate lesions at low or high risk. A systematic review and meta-analysis. Endocrine 63(3):430–438. https://doi.org/10.1007/s12020-018-1825-8
Trimboli P, Fulciniti F, Merlo E, Barizzi J, Mazzucchelli L, Giovanella L (2018) Histologic Outcome of Indeterminate Thyroid Nodules Classified at Low or High Risk. Endocr Pathol 29(1):75–79. https://doi.org/10.1007/s12022-018-9517-8
Haugen BR, Sawka AM, Alexander EK, Bible KC, Caturegli P, Doherty GM, Mandel SJ, Morris JC, Nassar A, Pacini F, Schlumberger M, Schuff K, Sherman SI, Somerset H, Sosa JA, Steward DL, Wartofsky L, Williams MD (2017) American Thyroid Association Guidelines on the management of thyroid nodules and differentiated thyroid cancer task force review and recommendation on the proposed renaming of encapsulated follicular variant papillary thyroid carcinoma without invasion to noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Thyroid 27(4):481–483. https://doi.org/10.1089/thy.2016.0628
Grani G, Lamartina L, Ascoli V, Bosco D, Nardi F, D'Ambrosio F, Rubini A, Giacomelli L, Biffoni M, Filetti S, Durante C, Cantisani V (2017) Ultrasonography scoring systems can rule out malignancy in cytologically indeterminate thyroid nodules. Endocrine 57(2):256–261. https://doi.org/10.1007/s12020-016-1148-6
Ulisse S, Bosco D, Nardi F, Nesca A, D'Armiento E, Guglielmino V, De Vito C, Sorrenti S, Pironi D, Tartaglia F, Arcieri S, Catania A, Monti M, Filippini A, Ascoli V (2017) thyroid imaging reporting and data system score combined with the New Italian Classification for Thyroid Cytology improves the clinical management of indeterminate nodules. Int J Endocrinol 2017:9692304. https://doi.org/10.1155/2017/9692304
Campanella P, Ianni F, Rota CA, Corsello SM, Pontecorvi A (2014) Quantification of cancer risk of each clinical and ultrasonographic suspicious feature of thyroid nodules: a systematic review and meta-analysis. Eur J Endocrinol 170(5):R203–211. https://doi.org/10.1530/EJE-13-0995
Ianni F, Campanella P, Rota CA, Prete A, Castellino L, Pontecorvi A, Corsello SM (2016) A meta-analysis-derived proposal for a clinical, ultrasonographic, and cytological scoring system to evaluate thyroid nodules: the "CUT" score. Endocrine 52(2):313–321. https://doi.org/10.1007/s12020-015-0785-5
Garino F, Deandrea M, Motta M, Mormile A, Ragazzoni F, Palestini N, Freddi M, Gasparri G, Sgotto E, Pacchioni D, Limone PP (2015) Diagnostic performance of elastography in cytologically indeterminate thyroid nodules. Endocrine 49(1):175–183. https://doi.org/10.1007/s12020-014-0438-0
Cipolletta Campanile A, Malzone MG, Losito NS, Botti G, Chiofalo MG, Faggiano A, Siciliano R, Colao A, Pezzullo L, Fulciniti F (2017) Accuracy of fine needle cytology in histological prediction of papillary thyroid carcinoma variants: a prospective study. Endocr Pathol 28(3):187–197. https://doi.org/10.1007/s12022-017-9488-1
Rago T, Scutari M, Latrofa F, Loiacono V, Piaggi P, Marchetti I, Romani R, Basolo F, Miccoli P, Tonacchera M, Vitti P (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 a more cumbersome cancer disease. J Clin Endocrinol Metabol 99(10):3700–3707. https://doi.org/10.1210/jc.2013-4401
Fadda G, Basolo F, Bondi A, Bussolati G, Crescenzi A, Nappi O, Nardi F, Papotti M, Taddei G, Palombini L, Group S.-I.I.C.W. (2010) Cytological classification of thyroid nodules Proposal of the SIAPEC-IAP Italian Consensus Working Group. Pathologica 102(5):405–408
Rullo E, Minelli G, Bosco D, Nardi F, Grani G, Durante C, Ascoli V (2019) Indeterminate thyroid nodules (TIR3A/TIR3B) according to the new Italian Reporting System for Thyroid Cytology: a cytomorphological study. Cytopathology. https://doi.org/10.1111/cyt.12732
Sparano C, Parenti G, Cilotti A, Bencini L, Calistri M, Mannucci E, Biagini C, Vezzosi V, Mannelli M, Forti G, Petrone L (2019) Clinical impact of the new SIAPEC-IAP classification on the indeterminate category of thyroid nodules. J Endocrinol Invest 42(1):1–6. https://doi.org/10.1007/s40618-018-0871-7
Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 295(18):2164–2167. https://doi.org/10.1001/jama.295.18.2164
Straccia P, Santoro A, Rossi ED, Brunelli C, Mosseri C, Musarra T, Pontecorvi A, Lombardi CP, Fadda G (2017) Incidence, malignancy rates of diagnoses and cyto-histological correlations in the new Italian Reporting System for Thyroid Cytology: an institutional experience. Cytopathology 28(6):503–508. https://doi.org/10.1111/cyt.12455
Rago T, Vitti P (2014) Diagnostic role of ultrasound and elastosonography in nodular goiter. Best practice and research. Clin Endocrinol Metabol 28(4):519–529. https://doi.org/10.1016/j.beem.2014.02.003
Moon HJ, Kwak JY, Kim MJ, Son EJ, Kim EK (2010) Can vascularity at power Doppler US help predict thyroid malignancy? Radiology 255(1):260–269. https://doi.org/10.1148/radiol.09091284
Frates MC, Benson CB, Doubilet PM, Cibas ES, Marqusee E (2003) Can color Doppler sonography aid in the prediction of malignancy of thyroid nodules? J Ultrasound Med 22(2):127–131. https://doi.org/10.7863/jum.2003.22.2.127
Papini E, Guglielmi R, Bianchini A, Crescenzi A, Taccogna S, Nardi F, Panunzi C, Rinaldi R, Toscano V, Pacella CM (2002) Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features. J Clin Endocrinol Metabol 87(5):1941–1946. https://doi.org/10.1210/jcem.87.5.8504
Brunese L, Romeo A, Iorio S, Napolitano G, Fucili S, Biondi B, Vallone G, Sodano A (2008) A new marker for diagnosis of thyroid papillary cancer: B-flow twinkling sign. J Ultrasound Med 27(8):1187–1194. https://doi.org/10.7863/jum.2008.27.8.1187
Frates MC, Benson CB, Charboneau JW, Cibas ES, Clark OH, Coleman BG, Cronan JJ, Doubilet PM, Evans DB, Goellner JR, Hay ID, Hertzberg BS, Intenzo CM, Jeffrey RB, Langer JE, Larsen PR, Mandel SJ, Middleton WD, Reading CC, Sherman SI, Tessler FN, Society of Radiologists in, U (2005) Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Radiology 237(3):794–800. https://doi.org/10.1148/radiol.2373050220
Rago T, Vitti P, Chiovato L, Mazzeo S, De Liperi A, Miccoli P, Viacava P, Bogazzi F, Martino E, Pinchera A (1998) Role of conventional ultrasonography and color flow-doppler sonography in predicting malignancy in 'cold' thyroid nodules. Eur J Endocrinol 138(1):41–46. https://doi.org/10.1530/eje.0.1380041
Iannuccilli JD, Cronan JJ, Monchik JM (2004) Risk for malignancy of thyroid nodules as assessed by sonographic criteria: the need for biopsy. J Ultrasound Med 23(11):1455–1464. https://doi.org/10.7863/jum.2004.23.11.1455
Vickery AL (1983) Thyroid papillary carcinoma. Pathological and philosophical controversies. Am J Surg Pathol 7(8):797–807
Ross DS (1991) Evaluation of the thyroid nodule. J Nucl Med 32(11):2181–2192
Sabel MS, Haque D, Velasco JM, Staren ED (1998) Use of ultrasound-guided fine needle aspiration biopsy in the management of thyroid disease. Am Surg 64(8):738–741
Macerola E, Rago T, Proietti A, Basolo F, Vitti P (2019) The mutational analysis in the diagnostic work-up of thyroid nodules: the real impact in a center with large experience in thyroid cytopathology. J Endocrinol Invest 42(2):157–166. https://doi.org/10.1007/s40618-018-0895-z
Castagna MG, Marzocchi C, Pilli T, Forleo R, Pacini F, Cantara S (2019) MicroRNA expression profile of thyroid nodules in fine-needle aspiration cytology: a confirmatory series. J Endocrinol Invest 42(1):97–100. https://doi.org/10.1007/s40618-018-0880-6
Cantisani V, Maceroni P, D'Andrea V, Patrizi G, Di Segni M, De Vito C, Grazhdani H, Isidori AM, Giannetta E, Redler A, Frattaroli F, Giacomelli L, Di Rocco G, Catalano C, D'Ambrosio F (2016) 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 26(5):1441–1449. https://doi.org/10.1007/s00330-015-3956-0
Magri F, Chytiris S, Chiovato L (2016) The role of elastography in thyroid ultrasonography. Curr Opin Endocrinol Diabetes Obes 23(5):416–422. https://doi.org/10.1097/MED.0000000000000274
Acknowledgements
The authors wish to thank Daniela Bosco for providing cytopathology diagnosis and the staff at the Interdepartmental Experimental and Molecular Medicine Library (bmedsper) of Sapienza University of Rome for their help in the bibliographic search.
Funding
This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by AC, RP, AP, CP, ER and ES. All authors drafted the article and revised it critically for important intellectual content and final approval of the version to be published.
Corresponding author
Ethics declarations
Conflict of interest
The authors report no conflict of interests that could be perceived as prejudicing the impartiality of the research reported.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional ethics committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent
All patients provided written informed consent for their participation.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Cozzolino, A., Pozza, C., Pofi, R. et al. Predictors of malignancy in high-risk indeterminate (TIR3B) cytopathology thyroid nodules. J Endocrinol Invest 43, 1115–1123 (2020). https://doi.org/10.1007/s40618-020-01200-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-020-01200-0