CARE: A Molecular-Guided Foundation Model with Adaptive Region Modeling for Whole Slide Image Analysis

Foundation models have recently achieved impressive success in computational pathology, demonstrating strong generalization across diverse histopathology tasks. However, existing models overlook the heterogeneous and non-uniform organization of pathological regions of interest (ROIs) because they rely on natural image backbones not tailored for tissue morphology. Consequently, they often fail to capture the coherent tissue architecture beyond isolated patches, limiting interpretability and clinical relevance. To address these challenges, we present Cross-modal Adaptive Region Encoder (CARE), a foundation model for pathology that automatically partitions WSIs into several morphologically relevant regions. Specifically, CARE employs a two-stage pretraining strategy: (1) a self-supervised unimodal pretraining stage that learns morphological representations from 34,277 whole-slide images (WSIs) without segmentation annotations, and (2) a cross-modal alignment stage that leverages RNA and protein profiles to refine the construction and representation of adaptive regions. This molecular guidance enables CARE to identify biologically relevant patterns and generate irregular yet coherent tissue regions, selecting the most representative area as ROI. CARE supports a broad range of pathology-related tasks, using either the ROI feature or the slide-level feature obtained by aggregating adaptive regions. Based on only one-tenth of the pretraining data typically used by mainstream foundation models, CARE achieves superior average performance across 33 downstream benchmarks, including morphological classification, molecular prediction, and survival analysis, and outperforms other foundation model baselines overall.

HistoGym: A Reinforcement Learning Environment for Histopathological Image Analysis

In pathological research, education, and clinical practice, the decision-making process based on pathological images is critically important. This significance extends to digital pathology image analysis: its adequacy is demonstrated by the extensive information contained within tissue structures, which is essential for accurate cancer classification and grading. Additionally, its necessity is highlighted by the inherent requirement for interpretability in the conclusions generated by algorithms. For humans, determining tumor type and grade typically involves multi-scale analysis, which presents a significant challenge for AI algorithms. Traditional patch-based methods are inadequate for modeling such complex structures, as they fail to capture the intricate, multi-scale information inherent in whole slide images. Consequently, there is a pressing need for advanced AI techniques capable of efficiently and accurately replicating this complex analytical process. To address this issue, we introduce HistoGym, an open-source reinforcement learning environment for histopathological image analysis. Following OpenAI Gym APIs, HistoGym aims to foster whole slide image diagnosis by mimicking the real-life processes of doctors. Leveraging the pyramid feature of WSIs and the OpenSlide API, HistoGym provides a unified framework for various clinical tasks, including tumor detection and classification. We detail the observation, action, and reward specifications tailored for the histopathological image analysis domain and provide an open-source Python-based interface for both clinicians and researchers. To accommodate different clinical demands, we offer various scenarios for different organs and cancers, including both WSI-based and selected region-based scenarios, showcasing several noteworthy results.