Pretraining Multiple Instance Learning Networks with Multi-Teacher Distillation from Pathology Slide Foundation Models

Multiple instance learning (MIL) has become the main paradigm for whole-slide image (WSI) analysis in computational pathology. However, existing MIL aggregators are still typically trained from scratch for each downstream task, relying on limited slide-level labels to learn both aggregation mechanisms and downstream discriminative representations simultaneously. As a result, they often suffer from unstable optimization, overfitting, and limited transferability. Similar to pretrained ResNet and Vision Transformer models in natural image learning, MIL also requires reusable pretrained initialization. However, high-quality slide-level pretraining data remain scarce, and MIL models are usually lightweight and weakly supervised, making large-scale pretraining difficult in practice. To address this challenge, we propose a distillation-based pretraining framework for MIL, which leverages two slide-level foundation models, TITAN and CARE, as teachers to transfer their representational knowledge into a diverse set of MIL architectures. To effectively balance supervision from different teachers, we further introduce an angular dispersion normalized distillation loss. The distilled weights are then used as initialization for downstream adaptation. We conduct systematic evaluations on 15 benchmark datasets under both linear probing and full-parameter fine-tuning, and further validate its advantages in few-shot scenarios. Experimental results show that pretraining generally improves MIL aggregators over from scratch training, especially in linear-probing and few-shot settings, while maintaining the computational efficiency of lightweight MIL models. Code is available at https://github.com/fu0201/MIL_Pretrained.

ALICE: Learning a General-Purpose Pathology Foundation Model from Vision, Vision-Language, and Slide-Level Experts

Foundation models are reshaping computational pathology, yet their capabilities remain shaped by pretraining objectives, data sources, and spatial scales, fragmenting complementary expertise across separate backbones. Here we present ALICE, a unified foundation model trained through multi-stage agglomerative distillation that sequentially distills eight vision-only, vision-language, and slide-level teacher models into dedicated modules of a single backbone. ALICE is pretrained on 24,985,184 tile-level pathology images and 155,604 high-resolution images, and evaluated across 21 task scenarios, 96 downstream tasks, and 48 data sources, spanning region-of-interest tissue analysis, vision-language multimodal evaluation, and whole-slide clinical assessment. In all three evaluation settings, ALICE achieved the best average rank among task-matched pathology foundation models. These results demonstrate that agglomerative distillation can consolidate complementary capabilities from specialized models into a unified backbone for broad computational pathology applications. The model is available at https://github.com/WonderLandxD/ALICE.

To What Extent Do Token-Level Representations from Pathology Foundation Models Improve Dense Prediction?

Pathology foundation models (PFMs) have rapidly advanced and are becoming a common backbone for downstream clinical tasks, offering strong transferability across tissues and institutions. However, for dense prediction (e.g., segmentation), practical deployment still lacks a clear, reproducible understanding of how different PFMs behave across datasets and how adaptation choices affect performance and stability. We present PFM-DenseBench, a large-scale benchmark for dense pathology prediction, evaluating 17 PFMs across 18 public segmentation datasets. Under a unified protocol, we systematically assess PFMs with multiple adaptation and fine-tuning strategies, and derive insightful, practice-oriented findings on when and why different PFMs and tuning choices succeed or fail across heterogeneous datasets. We release containers, configs, and dataset cards to enable reproducible evaluation and informed PFM selection for real-world dense pathology tasks. Project Website: https://m4a1tastegood.github.io/PFM-DenseBench

Multimodal Prototype Alignment for Semi-supervised Pathology Image Segmentation

Pathological image segmentation faces numerous challenges, particularly due to ambiguous semantic boundaries and the high cost of pixel-level annotations. Although recent semi-supervised methods based on consistency regularization (e.g., UniMatch) have made notable progress, they mainly rely on perturbation-based consistency within the image modality, making it difficult to capture high-level semantic priors, especially in structurally complex pathology images. To address these limitations, we propose MPAMatch - a novel segmentation framework that performs pixel-level contrastive learning under a multimodal prototype-guided supervision paradigm. The core innovation of MPAMatch lies in the dual contrastive learning scheme between image prototypes and pixel labels, and between text prototypes and pixel labels, providing supervision at both structural and semantic levels. This coarse-to-fine supervisory strategy not only enhances the discriminative capability on unlabeled samples but also introduces the text prototype supervision into segmentation for the first time, significantly improving semantic boundary modeling. In addition, we reconstruct the classic segmentation architecture (TransUNet) by replacing its ViT backbone with a pathology-pretrained foundation model (Uni), enabling more effective extraction of pathology-relevant features. Extensive experiments on GLAS, EBHI-SEG-GLAND, EBHI-SEG-CANCER, and KPI show MPAMatch's superiority over state-of-the-art methods, validating its dual advantages in structural and semantic modeling.

Deformable Attention Graph Representation Learning for Histopathology Whole Slide Image Analysis

Accurate classification of Whole Slide Images (WSIs) and Regions of Interest (ROIs) is a fundamental challenge in computational pathology. While mainstream approaches often adopt Multiple Instance Learning (MIL), they struggle to capture the spatial dependencies among tissue structures. Graph Neural Networks (GNNs) have emerged as a solution to model inter-instance relationships, yet most rely on static graph topologies and overlook the physical spatial positions of tissue patches. Moreover, conventional attention mechanisms lack specificity, limiting their ability to focus on structurally relevant regions. In this work, we propose a novel GNN framework with deformable attention for pathology image analysis. We construct a dynamic weighted directed graph based on patch features, where each node aggregates contextual information from its neighbors via attention-weighted edges. Specifically, we incorporate learnable spatial offsets informed by the real coordinates of each patch, enabling the model to adaptively attend to morphologically relevant regions across the slide. This design significantly enhances the contextual field while preserving spatial specificity. Our framework achieves state-of-the-art performance on four benchmark datasets (TCGA-COAD, BRACS, gastric intestinal metaplasia grading, and intestinal ROI classification), demonstrating the power of deformable attention in capturing complex spatial structures in WSIs and ROIs.

Subspecialty-Specific Foundation Model for Intelligent Gastrointestinal Pathology

Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis, heavily reliant on the subjective interpretation of pathologists, suffers from limited reproducibility and diagnostic variability. To overcome these limitations and address the lack of pathology-specific foundation models for GI diseases, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on more than 353 million image patches from over 200,000 hematoxylin and eosin-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, molecular prediction, gene mutation prediction, and prognosis evaluation, particularly in diagnostically ambiguous cases and resolution-agnostic tissue classification.We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.6% sensitivity across 9 independent medical institutions nationwide. The outstanding performance of Digepath highlights its potential to bridge critical gaps in histopathological practice. This work not only advances AI-driven precision pathology for GI diseases but also establishes a transferable paradigm for other pathology subspecialties.