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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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Graphical abstract

Abstract

Objective

The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods.

Methods

In total, 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006–2008, 2012–2014, 2017–2019). The distribution of diagnostic cytology, risk of malignancy, diagnostic performance indices of fine needle aspiration (FNA), and cytologic–histologic correlation in indeterminate cytology were analyzed.

Results

Only 2.2% of cytology tests were insufficient for a diagnosis. About 86.9% cytology was benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006–2008), 10.1% (2012–2014), and 10% (2017–2019). Surgery was performed in 13% of benign cytology, resulting in malignant histology in 2.7%. All malignant and suspicious cytology underwent surgery, with malignancy confirmed in 98% and 77% of cases, respectively.

All ‘indeterminate with atypia’ cytology (2006–2008) and Bethesda IV (2012–2014; 2017–2019) underwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the ‘indeterminate without atypia’ category (2006–2008) and Bethesda III (2012–2014; 2017–2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6%, with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods.

Conclusion

The Bethesda system reduces indeterminate cytology and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.

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