Transformation Behavior of Images in Latent Space

Magnification shift is a major obstacle to robust histopathology classification, because models trained on one imaging scale often generalize poorly to another. Here, we evaluated this problem on the BreaKHis dataset using a strict patient-disjoint leave-one-magnification-out protocol, comparing supervised baseline, baseline augmented with DCGAN-generated patches, and a gradient-reversal domain-general model designed to preserve discriminative information while suppressing magnification-specific variation. Across held-out magnifications, the domain-general model achieved the strongest overall discrimination and its clearest gain was observed when 200X was held out. By contrast, GAN augmentation produced inconsistent effects, improving some folds but degrading others, particularly at 400X. The domain-general model also yielded the lowest Brier score at 0.063 vs 0.089 at baseline. Sparse embedding analysis further revealed that domain-general training reduced average signature size more than three-fold (306 versus 1,074 dimensions) while preserving equivalent predictive performance (AUC: 0.967 vs 0.965; F1: 0.930 vs 0.931). It also increased cross-fold signature reproducibility from near-zero Jaccard overlap in the baseline to 0.99 between the 100X and 200X folds. These findings show that calibrated, compact, and transferable representations can be learned without added architectural complexity, with clear implications for the reliable deployment of computational pathology models across heterogeneous acquisition settings.

Synthetic histopathology image generation addresses critical challenges in computational pathology, including patient privacy and the growing need for large-scale training data for foundation models. Latent diffusion models have dominated the image generation domain, with recent works emphasizing that the choice of latent space is critical to the quality of generated images. Existing state-of-the-art generative models in histopathology use pretrained Vision Foundation Models (VFMs) as conditioning signals, and we observe that this leads to "conditioning collapse," where the conditioning signal dominates the latent space and lowers the quality and diversity of generated samples. Therefore, we instead use pretrained histopathology VFMs as the latent space itself, leveraging their patch-token features that encode rich semantic information. We empirically show that these features are $\ell_2$-normalized and lie on the unit hypersphere $\mathcal{S}^{d-1}$ with strong angular dominance and intrinsic curvature, making them naturally suited for a Riemannian formulation. We therefore present STREAM, the first framework to apply Riemannian flow matching in the pathology domain. STREAM consists of two stages: 1) a bridge-type stochastic perturbation that establishes per-token rectifiability on $\mathcal{S}^{d-1}$ for training a Diffusion Transformer (DiT) in latent space, and 2) a novel anisotropic decoder that allocates robustness to low-energy directions of the velocity-field Jacobian while preserving fidelity along its high-energy directions. Together, STREAM achieves state-of-the-art reconstruction and generation performance on breast and colorectal cancer datasets. The code will be publicly released upon acceptance.

Pathology foundation models improve transferable representation learning for histopathology, but recent gains often rely on encoders with hundreds of millions of parameters and high inference cost. We propose TAP-Path, a task-adaptive compression framework that directly restructures a pretrained Virchow2 encoder rather than distilling it into a separate student. TAP-Path combines validation-driven transformer-block selection, physical removal of redundant blocks, input-adaptive patch-token pruning, multi-depth feature recovery, and a lightweight gated task head. The final model retains 24 of 32 transformer blocks and 70% of patch tokens after pruning, reducing encoder parameters by 24.96% (631.24M to 473.70M) and analytical encoder compute by 35.20% (340.13G to 220.40G FLOPs). Across three task-head optimization seeds, TAP-Path achieved $87.98 \pm 0.067$ test accuracy, $81.26 \pm 0.49$ balanced accuracy, and $82.38 \pm 0.48$ macro-F1 on a 32-class histopathology benchmark, compared with 86.89% for full Virchow2 and 87.67% for UNI2-h. TAP-Path achieved a Brier score of $0.1800 \pm 0.0005$ and failure-detection AUROC of $0.9047 \pm 0.0060$. A validation-only rare-aware objective improved rare-class balanced accuracy in a secondary operating analysis. Frozen external evaluation on 433 CPTAC samples yielded $91.22 \pm 0.83$ accuracy and $91.10 \pm 0.81$ balanced accuracy. These results show that task-adaptive structural and token sparsification can improve the accuracy-efficiency trade-off of large pathology foundation models while preserving reliability under internal and external evaluation.