Physics-Grounded Adversarial Stain Augmentation with Calibrated Coverage Guarantees

Stain variation across hospitals degrades histopathology models at deployment. Existing augmentation methods perturb color spaces with arbitrary hyperparameters, lacking both a principled budget and coverage guarantees for unseen centers. We propose Calibrated Adversarial Stain Augmentation (CASA), which performs adversarial augmentation in the Macenko stain parameter space with a budget calibrated from multi-center statistics via the DKW inequality. On Camelyon17-WILDS (5 seeds), CASA achieves 93.9% ± 1.6% slide-level accuracy -- outperforming HED-strong (88.4% ± 7.3%), RandStainNA (85.2% ± 6.7%), and ERM (63.9% ± 11.3%) -- with the highest worst-group accuracy (84.9% ± 0.9%) among all 10 compared methods.