Microcalcification and Irregular Margins as Key Predictors of Thyroid Cancer: Integrated Analysis of EU-TIRADS, Bethesda, and Histopathology

Background and Objectives: Thyroid nodules are common, and distinguishing benign from malignant lesions is essential for clinical decision-making. While EU-TIRADS provides ultrasound-based risk stratification, fine-needle aspiration biopsy (FNAB) and the Bethesda System remain central diagnostic tools. This study aimed to compare the diagnostic performance of EU-TIRADS and Bethesda classifications and to identify ultrasonographic features independently associated with malignancy. Materials and Methods: This retrospective single-center study included 824 patients (1132 nodules) who underwent FNAB between August 2021 and June 2024. All ultrasound examinations and FNAB procedures were performed by the same endocrinologist. Sonographic features, EU-TIRADS categories, Bethesda classes, surgical indications, and histopathology were analyzed. Diagnostic accuracy was assessed using ROC curves, and multivariable logistic regression was applied to determine independent predictors of malignancy. Results: Among all nodules, 51.0% were EU-TIRADS 3, 28.6% were EU-TIRADS 4, and 19.2% were EU-TIRADS 5. Bethesda class II constituted 62.7% of FNAB results. Of the 289 surgically treated nodules, 53.3% were malignant. Malignant nodules were smaller, more often solitary and unilateral, and more frequently located in the upper pole (p < 0.05). Irregular margins (OR = 8.15, p < 0.001) and microcalcifications (OR = 10.01, p = 0.003) were independent predictors of malignancy. Taller-than-wide shape also showed significant association. ROC analyses demonstrated that EU-TIRADS (AUC = 0.808) and Bethesda (AUC = 0.869) were both significant predictors, with Bethesda showing higher specificity. Malignancy rates were 0% in EU-TIRADS II, 4.3% in III, 14.5% in IV, and 37.8% in V. Conclusions: EU-TIRADS is a practical and sensitive non-invasive tool for malignancy risk stratification; however, Bethesda classification remains superior in overall diagnostic accuracy. Microcalcification and irregular margins were the strongest ultrasonographic predictors of malignancy, while macrocalcification, parenchymal heterogeneity, and thyroiditis showed no significant association. These findings support the complementary roles of EU-TIRADS and FNAB and highlight key sonographic markers that enhance malignancy prediction in thyroid nodule evaluation.