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Ana Isabel Álvarez-Mancha Department of Medicine, University of Malaga, Malaga, Spain
Department of Pathology, General University Hospital of Ciudad Real, Ciudad Real, Spain

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Isabel Mancha-Doblas Department of Medicine, University of Malaga, Malaga, Spain
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain

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María Molina-Vega Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain
The Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA-BIONAND Platform), University of Malaga, Malaga, Spain

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Diego Fernández-García Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain

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Ana María Gómez-Pérez Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain
The Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA-BIONAND Platform), University of Malaga, Malaga, Spain

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Elena Gallego-Domínguez Department of Medicine, University of Malaga, Malaga, Spain
Department of Pathology, Virgen de la Victoria University Hospital, Málaga, Spain

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María Victoria Ortega-Jiménez Department of Medicine, University of Malaga, Malaga, Spain
Department of Pathology, Virgen de la Victoria University Hospital, Málaga, Spain

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Isabel Hierro-Martín Department of Pathology, Virgen de la Victoria University Hospital, Málaga, Spain

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Francisco J Tinahones Department of Medicine, University of Malaga, Malaga, Spain
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain
The Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA-BIONAND Platform), University of Malaga, Malaga, Spain

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, 6 , 7 , 8 , 9 ). A cytological diagnosis carries a certain risk of malignancy (ROM), which has implications for clinical recommendations. While FNA is an efficient and cost-effective diagnostic procedure, it is important to note that histological

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Alessia Cozzolino Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Tiziana Filardi Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Ilaria Simonelli Service of Medical Statistics and Information Technology, Fatebenefratelli Foundation for Health Research and Education, Rome, Italy
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy

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Giorgio Grani Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Camilla Virili Endocrinology Unit, Department of Medico-Surgical Sciences and Biotechnologies, ‘Sapienza’ University of Rome, Latina, Italy

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Ilaria Stramazzo Endocrinology Unit, Department of Medico-Surgical Sciences and Biotechnologies, ‘Sapienza’ University of Rome, Latina, Italy

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Maria Giulia Santaguida Endocrinology Unit, Department of Medico-Surgical Sciences and Biotechnologies, ‘Sapienza’ University of Rome, Latina, Italy

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Pietro Locantore Endocrinology Unit, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

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Massimo Maurici Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy

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Daniele Gianfrilli Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Andrea M Isidori Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Cosimo Durante Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Carlotta Pozza Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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on behalf of TALENT Group
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on behalf of TALENT Group

observational studies, mostly retrospective, have been conducted to identify the US features associated with the risk of malignancy in pediatric thyroid nodules. In 2016, they have been summarized in a meta-analysis reporting that the presence of internal

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J L Reverter Endocrinology and Nutrition Service, Germans Trias i Pujol Hospital and Research Institute, Badalona, Spain
Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

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L Ferrer-Estopiñan Endocrinology and Nutrition Service, Germans Trias i Pujol Hospital and Research Institute, Badalona, Spain
Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

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F Vázquez Endocrinology and Nutrition Service, Germans Trias i Pujol Hospital and Research Institute, Badalona, Spain
Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

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S Ballesta Endocrinology and Nutrition Service, Germans Trias i Pujol Hospital and Research Institute, Badalona, Spain
Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

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S Batule Endocrinology and Nutrition Service, Germans Trias i Pujol Hospital and Research Institute, Badalona, Spain
Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

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A Perez-Montes de Oca Endocrinology and Nutrition Service, Germans Trias i Pujol Hospital and Research Institute, Badalona, Spain
Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

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C Puig-Jové Endocrinology and Nutrition Service, Germans Trias i Pujol Hospital and Research Institute, Badalona, Spain
Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

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M Puig-Domingo Endocrinology and Nutrition Service, Germans Trias i Pujol Hospital and Research Institute, Badalona, Spain
Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

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nodules has enhanced the need for endocrinologists to be able to define the risk of malignancy as accurately as possible ( 2 ). Ultrasound (US) is the first-line method to identify malignant thyroid nodules with the advantages of accessibility, cost

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Tommaso Piticchio Endocrinology Section, Department of Clinical and Experimental Medicine, Garibaldi Nesima Hospital, University of Catania, Catania, Italy
Servizio di Endocrinologia e Diabetologia, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland

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Gilles Russ Department of Thyroid and Endocrine Tumor Diseases, La Pitie-Salpetriere Hospital, 83 Bd de l’Hopital, Paris, France

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Maija Radzina Riga Stradins University, Radiology Research Laboratory, Riga, Latvia
University of Latvia, Faculty of Medicine, Riga, Latvia

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Francesco Frasca Endocrinology Section, Department of Clinical and Experimental Medicine, Garibaldi Nesima Hospital, University of Catania, Catania, Italy

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Cosimo Durante Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Pierpaolo Trimboli Servizio di Endocrinologia e Diabetologia, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
Facoltà di Scienze Biomediche, Università della Svizzera Italiana (USI), Lugano, Switzerland

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-tiered scoring system (mild, moderate, severe) based on the estimated risk of malignancy. The most renowned TIRADSs from three different continents, specifically ACR-, EU-, and K-TIRADS ( 11 , 12 , 13 ), were evaluated, and their data were directly compared

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Stamatina Ioakim CEDM, Centre of Endocrinology, Diabetes & Metabolism, Limassol, Cyprus
Medical School, University of Milan, Milan, Italy

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Akheel A Syed Department of Diabetes, Endocrinology & Obesity Medicine, Salford Royal NHS Foundation & University Teaching Trust, Salford, UK
Division of Diabetes, Endocrinology & Gastroenterology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK

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George Zavros CEDM, Centre of Endocrinology, Diabetes & Metabolism, Limassol, Cyprus

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Michalis Picolos Alithias Endocrinology Centre, Nicosia, Cyprus

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Luca Persani Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Department of Endocrinology and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy

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Angelos Kyriacou CEDM, Centre of Endocrinology, Diabetes & Metabolism, Limassol, Cyprus
Department of Diabetes, Endocrinology & Obesity Medicine, Salford Royal NHS Foundation & University Teaching Trust, Salford, UK
Medical School, European University of Cyprus, Nicosia, Cyprus

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). Reassuringly, a recent long-term study of a 17,500-patient cohort with nodules greater than 10 mm in size showed an even lower risk of malignancy at 1.1% ( 6 ). The latter study differed from previous studies in that there was less selection bias and papillary

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Maria Mavromati Department of Endocrinology, Diabetology, Nutrition and Therapeutic Education, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva University, Geneva, Switzerland

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Essia Saiji Department of Pathology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Marco Stefano Demarchi Department of Endocrine Surgery, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Vincent Lenoir Department of Radiology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Amanda Seipel Department of Pathology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Paulina Kuczma Department of Endocrine Surgery, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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François R Jornayvaz Department of Endocrinology, Diabetology, Nutrition and Therapeutic Education, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva University, Geneva, Switzerland

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Minerva Becker Department of Radiology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Eugenio Fernandez Department of Oncology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Claudio De Vito Department of Pathology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Frédéric Triponez Department of Endocrine Surgery, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Sophie Leboulleux Department of Endocrinology, Diabetology, Nutrition and Therapeutic Education, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva University, Geneva, Switzerland

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, ultrasound scores are used to determine which nodules should undergo FNAC and the Bethesda classification is used to assess management based on the risk of malignancy ( 7 , 8 ). Suspicious nodules with Bethesda III, Bethesda IV, and Bethesda V cytology

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Laura Fugazzola Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Maurilio Deandrea Endocrinology, Diabetes and Metabolism Department and Center for Thyroid Diseases, Ordine Mauriziano Hospital, Turin, Italy

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Stefano Borgato Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Marco Dell’Acqua Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Francesca Retta Endocrinology, Diabetes and Metabolism Department and Center for Thyroid Diseases, Ordine Mauriziano Hospital, Turin, Italy

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Alberto Mormile Endocrinology, Diabetes and Metabolism Department and Center for Thyroid Diseases, Ordine Mauriziano Hospital, Turin, Italy

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Chiara Carzaniga Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Giacomo Gazzano Pathology Unit, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Gabriele Pogliaghi Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

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Marina Muzza Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Luca Persani Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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( 5 ), nodules classified as atypia of undetermined significance or follicular lesion of undetermined significance – AUS/FLUS, Bethesda III – harbor a risk of malignancy of 22% (range: 13–30%) and the recommended management is to repeat cytology or to

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Cosimo Durante Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Laszlo Hegedüs Department of Endocrinology, Odense University Hospital, Odense, Denmark

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Agnieszka Czarniecka M. Sklodowska-Curie National Research, Institute of Oncology Gliwice Branch, Gliwice, Poland

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Ralf Paschke Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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Gilles Russ Thyroid and Endocrine Tumors Department, Pitié-Salpêtrière Hospital, Sorbonne University GRC N°16, Paris, France

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Fernando Schmitt Faculty of Medicine of University of Porto, CINTESIS@RISE and Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto, Portugal

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Paula Soares Institute of Investigation and Innovation in Health (I3S), Faculty of Medicine of the University of Porto, Porto, Portugal

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Tamas Solymosi Endocrinology and Metabolism Clinic, Bugat Hospital, Gyöngyös, Hungary

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Enrico Papini Department of Endocrine and Metabolic Diseases, Regina Apostolorum Hospital, Albano, Rome, Italy

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-thyroidal extension. CNB, core-needle biopsy; FNA, fine-needle aspiration; ROM, risk of malignancy; US, ultrasound. Table 1 Summary of recommendations. a Initial evaluation Initial evaluation should include personal and family

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Pi-Ling Chiang Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan

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Sheng-Dean Luo Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Yen-Hsiang Chang Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Chen-Kai Chou Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Shun-Yu Chi Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Departments of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

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Yi-Fan Chen Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan

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Wei-Che Lin Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Thyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
Department of Radiology, Jen-Ai Hospital, Dali Branch, Taichung, Taiwan
School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung City, Taiwan

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. Previous studies have reported a consecutive AUS/FLUS diagnosis in 38.5% of patients, while 42.7–63.5% of repeat FNACs were found to be benign ( 13 , 17 ). The risk of malignancy (ROM) in thyroid nodules classified as Bethesda III (AUS/FLUS) is 10

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X Y Hu Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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J Wu Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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P Seal EFW Radiology, Calgary, Alberta, Canada

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S A Ghaznavi Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Department of Medicine, Section of Endocrinology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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C Symonds Department of Medicine, Section of Endocrinology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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S Kinnear Department of Medicine, Section of Endocrinology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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R Paschke Department of Medicine, Section of Endocrinology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Departments of Medicine, Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology, and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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that when a thyroid nodule FNA result is indeterminate, the ATA and ACR-TIRADS risk classification of the nodule can be very useful in estimating the risk of malignancy ( 10 , 11 , 12 , 13 ). Depending on the Bethesda category of the nodule, the

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