Validation of Diagnostic Utility of Washout CYFRA 21-1 in Lymph Node Metastasis of Thyroid Cancer

PURPOSE: Traditional methods, fine-needle aspiration cytology (FNAC), and washout thyroglobulin (Tg) do not always provide sufficient accuracy for diagnosing lymph node (LN) metastasis in thyroid cancer. This study aimed to validate the diagnostic performance of washout cytokeratin fragment 21-1 (CYFRA 21-1) as a complementary biomarker for diagnosing metastatic LN in thyroid cancer and to explore its relationship with molecular analysis and distant metastasis. EXPERIMENTAL DESIGN: In this retrospective cohort study involving 230 LN in 224 patients with papillary thyroid carcinoma, FNAC, washout Tg, and washout CYFRA 21-1 levels were measured in suspicious LN. The final LN outcomes were confirmed by surgical histology. RESULTS: Among the 230 LN, 145 (63.0%) were benign and 85 (37.0%) were metastatic. The optimal cutoff value for washout CYFRA 21-1 was established at 1.12 ng/mL (AUC, 0.959; 95% confidence interval, 0.936-0.982) with sensitivity of 93.4% and specificity of 97.8%. The cutoff value for washout Tg was 12.61 ng/mL (AUC, 0.832; 95% confidence interval, 0.772-0.892). The diagnostic performance of CYFRA 21-1 remained consistent across the preoperative (1.14 ng/mL) and postoperative assessment (1.10 ng/mL). The combination of FNAC and washout CYFRA 21-1 showed higher sensitivity (92.5%), specificity (95.9%), negative predictive value (93.7%), and diagnostic accuracy (95.1%) than the combination of FNAC and washout Tg. The washout CYFRA 21-1 level was associated with TERT mutations (OR, 3.35; P < 0.001), LN metastasis (OR, 5.43; P = 0.019), and distant metastasis (OR, 4.27; P = 0.019). CONCLUSIONS: Incorporating washout CYFRA 21-1 into the diagnostic process improves the accuracy of metastatic LN detection in thyroid cancer.