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.

HAAF: Hierarchical Adaptation and Alignment of Foundation Models for Few-Shot Pathology Anomaly Detection

Precision pathology relies on detecting fine-grained morphological abnormalities within specific Regions of Interest (ROIs), as these local, texture-rich cues - rather than global slide contexts - drive expert diagnostic reasoning. While Vision-Language (V-L) models promise data efficiency by leveraging semantic priors, adapting them faces a critical Granularity Mismatch, where generic representations fail to resolve such subtle defects. Current adaptation methods often treat modalities as independent streams, failing to ground semantic prompts in ROI-specific visual contexts. To bridge this gap, we propose the Hierarchical Adaptation and Alignment Framework (HAAF). At its core is a novel Cross-Level Scaled Alignment (CLSA) mechanism that enforces a sequential calibration order: visual features first inject context into text prompts to generate content-adaptive descriptors, which then spatially guide the visual encoder to spotlight anomalies. Additionally, a dual-branch inference strategy integrates semantic scores with geometric prototypes to ensure stability in few-shot settings. Experiments on four benchmarks show HAAF significantly outperforms state-of-the-art methods and effectively scales with domain-specific backbones (e.g., CONCH) in low-resource scenarios.