SAGE: Semantic Explainability of Attention-Based Survival Models in Computational Pathology

Attention-based multiple instance learning (ABMIL) is the predominant approach for slide-level prediction in computational pathology, yet its attention maps provide only local explanations: they indicate where a model focuses but not which histological features drive its predictions or how the model behaves across a patient cohort. We present Semantic Attention Global Explanations (SAGE), a post-hoc framework that extracts global, language-grounded explanations from a frozen ABMIL model. Using a pathology vision-language model, SAGE scores image patches against a dictionary of 25 histological concepts, aggregates these scores according to the model's learned attention, and quantifies how each concept relates to prediction risk across a cohort. Applied to survival prediction using seven TCGA cancer cohorts and three foundation models, SAGE recovered established prognostic features, such as the adverse association of necrosis, while revealing cancer-specific biology, including a favorable angiogenic signature in renal cell carcinoma consistent with known molecular subtypes. Ablation studies demonstrated that these associations depend on the model's learned attention rather than concept prevalence alone, and that the concept dictionary captures much of the prognostic information encoded by the foundation model features. Through semantically-grounded explanations, SAGE provides a scalable, model-agnostic framework for understanding what ABMIL survival models learn, enabling pathologists to interpret model behavior at the cohort level and offering the potential for biomarker identification.

Do Pathology Foundation Models Encode Disease Progression? A Pseudotime Analysis of Visual Representations

Vision foundation models trained on discretely sampled images achieve strong performance on classification benchmarks, yet whether their representations encode the continuous processes underlying their training data remains unclear. This question is especially pertinent in computational pathology, where we posit that models whose latent representations implicitly capture continuous disease progression may better reflect underlying biology, support more robust generalization, and enable quantitative analyses of features associated with disease transitions. Using diffusion pseudotime, a method developed to infer developmental trajectories from single-cell transcriptomics, we probe whether foundation models organize disease states along coherent progression directions in representation space. Across four cancer progressions and six models, we find that all pathology-specific models recover trajectory orderings significantly exceeding null baselines, with vision-only models achieving the highest fidelities $(τ> 0.78$ on CRC-Serrated). Model rankings by trajectory fidelity on reference diseases strongly predict few-shot classification performance on held-out diseases ($ρ= 0.92$), and exploratory analysis shows cell-type composition varies smoothly along inferred trajectories in patterns consistent with known stromal remodeling. Together, these results demonstrate that vision foundation models can implicitly learn to represent continuous processes from independent static observations, and that trajectory fidelity provides a complementary measure of representation quality beyond downstream performance. While demonstrated in pathology, this framework could be applied to other domains where continuous processes are observed through static snapshots.