Xinheng Lyu

Yuxuan Sun, Hao Wu, Chenglu Zhu et al.

The emergence of large multimodal models has unlocked remarkable potential in AI, particularly in pathology. However, the lack of specialized, high-quality benchmark impeded their development and precise evaluation. To address this, we introduce PathMMU, the largest and highest-quality expert-validated pathology benchmark for Large Multimodal Models (LMMs). It comprises 33,428 multimodal multi-choice questions and 24,067 images from various sources, each accompanied by an explanation for the correct answer. The construction of PathMMU harnesses GPT-4V's advanced capabilities, utilizing over 30,000 image-caption pairs to enrich captions and generate corresponding Q&As in a cascading process. Significantly, to maximize PathMMU's authority, we invite seven pathologists to scrutinize each question under strict standards in PathMMU's validation and test sets, while simultaneously setting an expert-level performance benchmark for PathMMU. We conduct extensive evaluations, including zero-shot assessments of 14 open-sourced and 4 closed-sourced LMMs and their robustness to image corruption. We also fine-tune representative LMMs to assess their adaptability to PathMMU. The empirical findings indicate that advanced LMMs struggle with the challenging PathMMU benchmark, with the top-performing LMM, GPT-4V, achieving only a 49.8% zero-shot performance, significantly lower than the 71.8% demonstrated by human pathologists. After fine-tuning, significantly smaller open-sourced LMMs can outperform GPT-4V but still fall short of the expertise shown by pathologists. We hope that the PathMMU will offer valuable insights and foster the development of more specialized, next-generation LMMs for pathology.

Jinyue Li, Yuci Liang, Qiankun Li et al.

Computational pathology demands both visual pattern recognition and dynamic integration of structured domain knowledge, including taxonomy, grading criteria, and clinical evidence. In practice, diagnostic reasoning requires linking morphological evidence with formal diagnostic and grading criteria. Although multimodal large language models (MLLMs) demonstrate strong vision language reasoning capabilities, they lack explicit mechanisms for structured knowledge integration and interpretable memory control. As a result, existing models struggle to consistently incorporate pathology-specific diagnostic standards during reasoning. Inspired by the hierarchical memory process of human pathologists, we propose PathMem, a memory-centric multimodal framework for pathology MLLMs. PathMem organizes structured pathology knowledge as a long-term memory (LTM) and introduces a Memory Transformer that models the dynamic transition from LTM to working memory (WM) through multimodal memory activation and context-aware knowledge grounding, enabling context-aware memory refinement for downstream reasoning. PathMem achieves SOTA performance across benchmarks, improving WSI-Bench report generation (12.8% WSI-Precision, 10.1% WSI-Relevance) and open-ended diagnosis by 9.7% and 8.9% over prior WSI-based models.

Yuci Liang, Xinheng Lyu, Wenting Chen et al.

Recent advancements in computational pathology have produced patch-level Multi-modal Large Language Models (MLLMs), but these models are limited by their inability to analyze whole slide images (WSIs) comprehensively and their tendency to bypass crucial morphological features that pathologists rely on for diagnosis. To address these challenges, we first introduce WSI-Bench, a large-scale morphology-aware benchmark containing 180k VQA pairs from 9,850 WSIs across 30 cancer types, designed to evaluate MLLMs' understanding of morphological characteristics crucial for accurate diagnosis. Building upon this benchmark, we present WSI-LLaVA, a novel framework for gigapixel WSI understanding that employs a three-stage training approach: WSI-text alignment, feature space alignment, and task-specific instruction tuning. To better assess model performance in pathological contexts, we develop two specialized WSI metrics: WSI-Precision and WSI-Relevance. Experimental results demonstrate that WSI-LLaVA outperforms existing models across all capability dimensions, with a significant improvement in morphological analysis, establishing a clear correlation between morphological understanding and diagnostic accuracy.

Jiaqi Yang, Wenting Chen, Xiaohan Xing et al.

Multimodal learning that integrates histopathology images and genomic data holds great promise for cancer survival prediction. However, existing methods face key limitations: 1) They rely on multimodal mapping and metrics in Euclidean space, which cannot fully capture the hierarchical structures in histopathology (among patches from different resolutions) and genomics data (from genes to pathways). 2) They discretize survival time into independent risk intervals, which ignores its continuous and ordinal nature and fails to achieve effective optimization. 3) They treat censorship as a binary indicator, excluding censored samples from model optimization and not making full use of them. To address these challenges, we propose HySurvPred, a novel framework for survival prediction that integrates three key modules: Multimodal Hyperbolic Mapping (MHM), Angle-aware Ranking-based Contrastive Loss (ARCL) and Censor-Conditioned Uncertainty Constraint (CUC). Instead of relying on Euclidean space, we design the MHM module to explore the inherent hierarchical structures within each modality in hyperbolic space. To better integrate multimodal features in hyperbolic space, we introduce the ARCL module, which uses ranking-based contrastive learning to preserve the ordinal nature of survival time, along with the CUC module to fully explore the censored data. Extensive experiments demonstrate that our method outperforms state-of-the-art methods on five benchmark datasets. The source code is to be released.

Guolin Huang, Wenting Chen, Jiaqi Yang et al.

Survival analysis is critical for cancer prognosis and treatment planning, yet existing methods lack the transparency essential for clinical adoption. While recent pathology agents have demonstrated explainability in diagnostic tasks, they face three limitations for survival prediction: inability to integrate multimodal data, ineffective region-of-interest exploration, and failure to leverage experiential learning from historical cases. We introduce SurvAgent, the first hierarchical chain-of-thought (CoT)-enhanced multi-agent system for multimodal survival prediction. SurvAgent consists of two stages: (1) WSI-Gene CoT-Enhanced Case Bank Construction employs hierarchical analysis through Low-Magnification Screening, Cross-Modal Similarity-Aware Patch Mining, and Confidence-Aware Patch Mining for pathology images, while Gene-Stratified analysis processes six functional gene categories. Both generate structured reports with CoT reasoning, storing complete analytical processes for experiential learning. (2) Dichotomy-Based Multi-Expert Agent Inference retrieves similar cases via RAG and integrates multimodal reports with expert predictions through progressive interval refinement. Extensive experiments on five TCGA cohorts demonstrate SurvAgent's superority over conventional methods, proprietary MLLMs, and medical agents, establishing a new paradigm for explainable AI-driven survival prediction in precision oncology.

Xinheng Lyu, Yuci Liang, Wenting Chen et al.

Whole slide images (WSIs) are vital in digital pathology, enabling gigapixel tissue analysis across various pathological tasks. While recent advancements in multi-modal large language models (MLLMs) allow multi-task WSI analysis through natural language, they often underperform compared to task-specific models. Collaborative multi-agent systems have emerged as a promising solution to balance versatility and accuracy in healthcare, yet their potential remains underexplored in pathology-specific domains. To address these issues, we propose WSI-Agents, a novel collaborative multi-agent system for multi-modal WSI analysis. WSI-Agents integrates specialized functional agents with robust task allocation and verification mechanisms to enhance both task-specific accuracy and multi-task versatility through three components: (1) a task allocation module assigning tasks to expert agents using a model zoo of patch and WSI level MLLMs, (2) a verification mechanism ensuring accuracy through internal consistency checks and external validation using pathology knowledge bases and domain-specific models, and (3) a summary module synthesizing the final summary with visual interpretation maps. Extensive experiments on multi-modal WSI benchmarks show WSI-Agents's superiority to current WSI MLLMs and medical agent frameworks across diverse tasks.