Jigsaw Regularization in Whole-Slide Image Classification

Whole slide images, with their gigapixel-scale panoramas of tissue samples, are pivotal for precise disease diagnosis. However, their analysis is hindered by immense data size and scarce annotations. Existing MIL methods face challenges due to the fundamental imbalance where a single bag-level label must guide the learning of numerous patch-level features. This sparse supervision makes it difficult to reliably identify discriminative patches during training, leading to unstable optimization and suboptimal solutions. We propose a spatially regularized MIL framework that leverages inherent spatial relationships among patch features as label-independent regularization signals. Our approach learns a shared representation space by jointly optimizing feature-induced spatial reconstruction and label-guided classification objectives, enforcing consistency between intrinsic structural patterns and supervisory signals. Experimental results on multiple public datasets demonstrate significant improvements over state-of-the-art methods, offering a promising direction.

Whole slide image (WSI) analysis in computational pathology follows a multiple instance learning (MIL) pipeline where patch embeddings are extracted independently and aggregated for slide-level prediction, but within-slide variance from staining, scanner, and local texture can overwhelm the discriminative signal. We propose Masked Feature Encoding for Multiple Instance Learning (MFE-MIL), a feature-space masking framework that trains a lightweight MLP adapter jointly with a window-based masked reconstruction branch and a MIL classification head. The two objectives are complementary. Classification guides the adapter to suppress within-slide patch variance, while window-based masked reconstruction provides an auxiliary regularizer for the adapted features without using patch coordinates, coordinate graphs, or segmentation preprocessing. The raster patch-extraction order is used only as a weak implicit prior. At inference, the decoder is removed, leaving only the adapter and MIL head. Across CAMELYON16/17, PANDA, and TCGA-BRCA with four diverse encoders, MFE-MIL improves ACC/F1 for nearly all tested aggregator-encoder settings and AUC in most, outperforms coordinate-based spatial methods (CAMIL), and achieves higher AUC than 2DMamba on three of four datasets (UNI). On five TCGA survival cohorts it improves the average concordance index for every aggregator tested, its most consistent gain. Code is available at https://github.com/AtlasAnalyticsLab/MFE-MIL.

Accurate analysis of histopathological images is critical for disease diagnosis and treatment planning. Whole-slide images (WSIs), which digitize tissue specimens at gigapixel resolution, are fundamental to this process but require aggregating thousands of patches for slide-level predictions. Multiple Instance Learning (MIL) tackles this challenge with a two-stage paradigm, decoupling tile-level embedding and slide-level prediction. However, most existing methods implicitly embed patch representations in homogeneous Euclidean spaces, overlooking the hierarchical organization and regional heterogeneity of pathological tissues. This limits current models' ability to capture global tissue architecture and fine-grained cellular morphology. To address this limitation, we introduce a hybrid hyperbolic-Euclidean representation that embeds WSI features in dual geometric spaces, enabling complementary modeling of hierarchical tissue structures and local morphological details. Building on this formulation, we develop BatMIL, a WSI classification framework that leverages both geometric spaces. To model long-range dependencies among thousands of patches, we employ a structured state space sequence model (S4) backbone that encodes patch sequences with linear computational complexity. Furthermore, to account for regional heterogeneity, we introduce a chunk-level mixture-of-experts (MoE) module that groups patches into regions and dynamically routes them to specialized subnetworks, improving representational capacity while reducing redundant computation. Extensive experiments on seven WSI datasets spanning six cancer types demonstrate that BatMIL consistently outperforms state-of-the-art MIL approaches in slide-level classification tasks. These results indicate that geometry-aware representation learning offers a promising direction for next-generation computational pathology.