Antibody-Stratified FNA-Thyroglobulin Cut-Off Values for Preoperative Lymph Node Assessment in Differentiated Thyroid Cancer.

Background: Fine-needle aspiration thyroglobulin (FNA-Tg) is widely used to detect lymph node metastases in differentiated thyroid cancer (DTC), but optimal cut-off values remain controversial. Anti-thyroglobulin antibodies (anti-Tg), present in 25-40% of DTC patients, may interfere with FNA-Tg measurements. This study aimed to evaluate whether anti-Tg status necessitates different FNA-Tg diagnostic thresholds in the preoperative setting. Methods: We retrospectively analyzed 605 cervical lymph nodes from 393 preoperative DTC patients who underwent ultrasound-guided fine-needle aspiration (FNA) with concurrent FNA-Tg measurement (February 2019-April 2025). All lymph nodes had histopathological or cytological confirmation. Patients were stratified by anti-Tg status (>4.5 IU/mL). Receiver operating characteristic curve analysis determined optimal FNA-Tg cut-offs, and areas under the curve (AUCs) were compared using the DeLong test. Results: FNA-Tg demonstrated excellent overall diagnostic accuracy (AUC 0.963, 95% CI 0.946-0.980) with an optimal cut-off of 84.0 ng/mL (sensitivity 91.6%, specificity 95.3%). Anti-Tg-positive patients had significantly lower FNA-Tg levels in malignant lymph nodes compared to anti-Tg-negative patients (median 9872 vs. 22,327 ng/mL, p = 0.001). Subgroup analysis revealed superior performance in anti-Tg-negative patients (AUC 0.983, cut-off 84.4 ng/mL) compared to anti-Tg-positive patients (AUC 0.923, cut-off 65.7 ng/mL; p = 0.008). No significant correlation was observed between anti-Tg levels and FNA-Tg (ρ = -0.03, p = 0.501). Conclusions: Anti-Tg status influenced measured FNA-Tg levels and receiver operating characteristic (ROC) derived optimal thresholds in the preoperative setting. However, because malignant lymph nodes generally showed FNA-Tg values well above the benign range, the clinical impact of this difference appears limited in most clearly positive cases. These findings may still help refine interpretation in selected borderline cases.