Hemodynamic response after preoperative embolization in thymoma-associated myasthenia gravis: associations with necrosis, HIF-1α expression, and CD163-positive macrophages.

BACKGROUND: Thymoma-associated myasthenia gravis is a distinct clinicopathological setting in which thymic epithelial tumor biology, autoimmunity, and perioperative neurological risk overlap. In selected hypervascular thymomas, preoperative transarterial embolization is used before surgical resection, but the tissue-level correlates of the angiographic response remain unclear. METHODS: This single-center retrospective translational cohort study included 64 patients with thymoma-associated myasthenia gravis who underwent clinically indicated preoperative embolization followed by thymectomy between January 2018 and June 2025. The primary exposure was angiographic tumor blush reduction measured on digital subtraction angiography. Primary outcomes were tumor necrosis proportion, HIF-1α H-score, and CD163-positive macrophage density. Patients were descriptively stratified into low-, intermediate-, and high-response groups according to tumor blush reduction, while continuous blush reduction was retained for regression analyses. RESULTS: Among 214 screened patients with thymic epithelial tumors, 64 met the eligibility criteria. Median tumor blush reduction was 56.2%. Tumor necrosis proportion increased across the low-, intermediate-, and high-response groups, with values of 30.6% ± 19.4%, 40.2% ± 23.5%, and 56.1% ± 24.6%, respectively (P = 0.003; FDR q = 0.036). HIF-1α H-score showed a similar pattern (111.4 ± 51.6, 134.8 ± 60.3, and 169.5 ± 61.0; P = 0.008; FDR q = 0.048). CAIX and CD163-positive macrophage density showed unadjusted between-group differences, whereas VEGF-A, CD8-positive T-cell density, FOXP3-positive T-cell density, PD-L1 tumor proportion score, CD8/FOXP3 ratio, and the composite immune-enriched phenotype showed broader overlap across groups. Exploratory CD20 and CXCL13 analyses did not show a graded increase across hemodynamic response strata. In multivariable analyses, each 10% increase in tumor blush reduction was associated with greater necrosis proportion and higher HIF-1α H-score. The association between blush reduction and HIF-1α H-score was attenuated after adjustment for necrosis proportion. Exploratory postoperative MG outcomes did not show a clear graded association with angiographic response. CONCLUSION: In embolized thymoma-associated myasthenia gravis, greater angiographic devascularization was associated mainly with ischemic necrosis and HIF-1α expression. Immune findings were heterogeneous, with CD163-positive macrophage density showing an exploratory signal rather than a uniform immune shift. These results support an association-based interpretation and require prospective validation.