Abstract
INTRODUCTION: Considering the importance of differentiating between benign and malignant thyroid nodules, this study explores the individual predictors of malignancy. Recent research has focused on individual predictors of isolation, but a comprehensive assessment of these predictors is essential to improve diagnostic accuracy and patient outcomes. METHODS: This comprehensive systematic review included seven articles after a rigorous screening of PubMed, PubMed Central, and MEDLINE databases and thus analyzed 1419 patients with indeterminate thyroid nodules using different determinants, such as genetic, biochemical, clinical, radiological, and cytological. RESULTS: Numerous independent indicators, such as a history of Hashimoto's thyroiditis, multinodular goiter, and past malignant history, were revealed as the strong clinical predictors of malignancy. Ultrasound (US) predictors such as neck lymphadenopathy, heterogeneity of internal echogenicity, long axis size ≥1.93 cm, and small-to-long axis ratio ≥ 0.64 are strong radiological indicators. Integrating cytology with elevated serum thyroglobulin levels has emerged as a strong cytological and biochemical indicator of malignancy. Other predictors, such as molecular testing, dual-spectral CT (DLCT), and the combination of US Thyroid Imaging Reporting And Data System (TI-RADS) and new US scoring systems were also identified. CONCLUSION: A multimodal diagnostic strategy has the potential to significantly improve diagnostic accuracy. While US and cytology remain the cornerstones of diagnosis, serum markers, molecular markers, and advanced imaging techniques, such as DLCT, can further enhance diagnostic accuracy. These independent characteristics warrant a risk stratification system, which could significantly improve diagnostic accuracy and patient outcomes.