Presepsin Outperforms Conventional Inflammatory Markers in Distinguishing Malignant from Benign Cervical Lymphadenopathy

<b>Objectives:</b> This study aimed to evaluate the diagnostic value of presepsin in differentiating benign and malignant causes of cervical lymphadenopathy and to compare its performance with conventional inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil-to-lymphocyte ratio (NLR). <b>Methods:</b> A total of 76 individuals were enrolled, including 52 patients who underwent excisional biopsy for cervical lymphadenopathy and 24 healthy controls. Serum presepsin, CRP, ESR, and complete blood count parameters were measured preoperatively. Patients were classified according to histopathological diagnosis as reactive, granulomatous, or malignant lymphadenopathy. Correlation and receiver operating characteristic (ROC) analyses were performed to assess the diagnostic performance of biomarkers. <b>Results:</b> Median presepsin, CRP, ESR, NLR, and monocyte-to-lymphocyte ratio (MLR) levels were significantly higher in the patient group compared with controls (all <i>p</i> < 0.001). Presepsin levels correlated positively with CRP (<i>r</i> = 0.42), ESR (<i>r</i> = 0.38), and NLR (<i>r</i> = 0.36). Although subgroup analysis revealed no statistically significant differences in presepsin levels among reactive, granulomatous, and malignant cases (<i>p</i> = 0.50), ROC analysis demonstrated the highest diagnostic accuracy for presepsin (AUC = 0.85), followed by CRP (AUC = 0.78), ESR (AUC = 0.74), and NLR (AUC = 0.72). A presepsin threshold of >210 pg/mL predicted malignancy with 82.4% sensitivity and 78.6% specificity. <b>Conclusions:</b> Presepsin provides an objective and noninvasive tool that complements traditional inflammatory markers in the diagnostic evaluation of cervical lymphadenopathy. Its superior diagnostic performance for malignancy prediction suggests potential utility in guiding biopsy decisions and avoiding unnecessary surgical procedures in benign cases.