Shortcut Learning in Glomerular AI: Adversarial Penalties Hurt, Entropy Helps

Glomerular pathology is central to the diagnosis and prognosis of renal diseases, yet the heterogeneity of glomerular morphology and fine-grained lesion patterns remain challenging for current AI approaches. We present GloPath, an entity-centric foundation model trained on over one million glomeruli extracted from 14,049 renal biopsy specimens using multi-scale and multi-view self-supervised learning. GloPath addresses two major challenges in nephropathology: glomerular lesion assessment and clinicopathological insights discovery. For lesion assessment, GloPath was benchmarked across three independent cohorts on 52 tasks, including lesion recognition, grading, few-shot classification, and cross-modality diagnosis-outperforming state-of-the-art methods in 42 tasks (80.8%). In the large-scale real-world study, it achieved an ROC-AUC of 91.51% for lesion recognition, demonstrating strong robustness in routine clinical settings. For clinicopathological insights, GloPath systematically revealed statistically significant associations between glomerular morphological parameters and clinical indicators across 224 morphology-clinical variable pairs, demonstrating its capacity to connect tissue-level pathology with patient-level outcomes. Together, these results position GloPath as a scalable and interpretable platform for glomerular lesion assessment and clinicopathological discovery, representing a step toward clinically translatable AI in renal pathology.

Fine-grained glomerular subtyping is essential for kidney biopsy interpretation, yet it presents a harder setting than the broad organ- or disease-level recognition tasks commonly used in vision-language model (VLM) evaluation. In this task, all categories arise within the same renal microanatomic unit, and clinically meaningful subtypes often differ by subtle, overlapping, and continuum-like morphological cues. Clinically valuable labels are also scarce, making fully supervised image-only paradigms difficult to translate to practice. Although VLMs are promising for data-efficient pathology learning, it remains unclear how their cross-modal representations should be adapted and evaluated for such within-structure discrimination under realistic few-shot constraints. To our knowledge, this study establishes the first fine-grained renal pathology benchmark for few-shot VLM adaptation and systematically examines how supervision level, model design, and adaptation strategy shape both classification performance and multimodal representation structure. Beyond accuracy, AUC, and F1, we assess image-text alignment, positive-negative similarity separation, embedding geometry, and calibration (ECE), asking when performance gains reflect more reliable cross-modal understanding. Across renal pathology cohorts, additional supervision consistently improves discrimination, but reliable adaptation is not explained by alignment alone; stronger performance is associated with larger class separation, more coherent embedding organization, and better awareness of confidence-related failure modes under domain variation. Within this retrospective two-cohort evaluation, these findings move assessment beyond coarse classification and accuracy alone and provide comparative evidence to inform model selection and future translational validation. Code: https://github.com/ddrrnn123/glo-vlms

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 $93.9\% \pm 1.6\%$ slide-level accuracy -- outperforming HED-strong ($88.4\% \pm 7.3\%$), RandStainNA ($85.2\% \pm 6.7\%$), and ERM ($63.9\% \pm 11.3\%$) -- with the highest worst-group accuracy ($84.9\% \pm 0.9\%$) among all 10 compared methods.