SPIO-enhanced MRI for differentiating metastatic from reactive hyperplastic lymph nodes in breast cancer: diagnostic performance and association with VEGF-C expression

Background Accurate assessment of lymph node status is essential for staging and treatment planning in breast cancer. Conventional morphological imaging criteria have limited sensitivity and specificity. Superparamagnetic Iron Oxide (SPIO)-enhanced MRI offers a functional imaging alternative exploiting macrophage-mediated iron uptake. This study evaluated the diagnostic performance of SPIO-enhanced MRI in differentiating metastatic from reactive hyperplastic lymph nodes and explored the association between MRI signal characteristics and Vascular Endothelial Growth Factor C (VEGF-C) expression. Methods Sixty female breast cancer patients (January–May 2024) underwent preoperative plain and SPIO-enhanced MRI (Resovist, 0.2 mL/kg, 12-h delay). Among 112 harvested lymph nodes, Hematoxylin and Eosin staining, Prussian Blue staining, and VEGF-C immunohistochemistry were performed. The Percentage of Signal Intensity Loss (PSIL) was calculated on T2*-weighted images. The primary diagnostic analysis was patient-level using mean PSIL with receiver operating characteristic analysis. Results Of 112 lymph nodes from 60 patients, 47 were metastatic and 65 reactive hyperplastic. Reactive nodes showed marked signal attenuation (mean PSIL 64.7 ± 12.0%) compared with metastatic nodes (11.6 ± 7.8%; p < 0.001). Patient-level ROC analysis yielded an area under the curve of 0.84 (95% CI: 0.73–0.95). At a data-derived optimal cutoff of 42% (Youden index), sensitivity was 83%, specificity 85%, positive predictive value 80.0%, negative predictive value 87.2%, and overall diagnostic accuracy 84.0%. Histopathological Prussian Blue grading supported differential iron uptake patterns between groups. High VEGF-C expression (≥++) was more prevalent in metastatic than hyperplastic nodes (85.1% vs. 12.3%; p < 0.001). PSIL showed a moderate inverse correlation with VEGF-C grade (Spearman r = −0.67; p < 0.001). Conclusion SPIO-enhanced MRI demonstrated favorable diagnostic performance for differentiating metastatic from reactive hyperplastic lymph nodes at the patient level. The imaging characteristics were associated with supportive histopathological findings and VEGF-C expression patterns. These findings warrant validation in larger, multicenter studies using currently available iron oxide agents.