Deep neural networks (DNNs) have significantly advanced diabetic retinopathy (DR) diagnosis, yet their black-box nature limits clinical acceptance due to a lack of interpretability. Concept bottleneck model (CBM) offers a promising solution by enabling concept-level reasoning and test-time intervention, with recent DR studies modeling lesions as concepts and grades as outcomes. However, current methods often ignore relationships between lesion concepts across different DR grades and struggle when fine-grained lesion concepts are unavailable, limiting their interpretability and real-world applicability. To bridge these gaps, we propose VLM-GCR, a vision-language model guided graph concept reasoning framework for interpretable DR diagnosis. VLM-GCR emulates the diagnostic process of ophthalmologists by constructing a grading-aware lesion concept graph that explicitly models the interactions among lesions and their relationships to disease grades. In concept-free clinical scenarios, our method introduces a vision-language guided dynamic concept pseudo-labeling mechanism to mitigate the challenges of existing concept-based models in fine-grained lesion recognition. Additionally, we introduce a multi-level intervention method that supports error correction, enabling transparent and robust human-AI collaboration. Experiments on two public DR benchmarks show that VLM-GCR achieves strong performance in both lesion and grading tasks, while delivering clear and clinically meaningful reasoning steps.

Recent advancements in Large Vision Language Models (LVLMs) show promise for pathological diagnosis, yet their application in clinical settings faces critical challenges of multimodal hallucination and biased responses. While preference alignment methods have proven effective in general domains, acquiring high-quality preference data for pathology remains challenging due to limited expert resources and domain complexity. In this paper, we propose EAGLE (Expert-guided self-enhancement for preference Alignment in patholoGy Large vision-languagE model), a novel framework that systematically integrates medical expertise into preference alignment. EAGLE consists of three key stages: initialization through supervised fine-tuning, self-preference creation leveraging expert prompting and medical entity recognition, and iterative preference following-tuning. The self-preference creation stage uniquely combines expert-verified chosen sampling with expert-guided rejected sampling to generate high-quality preference data, while the iterative tuning process continuously refines both data quality and model performance. Extensive experiments demonstrate that EAGLE significantly outperforms existing pathological LVLMs, effectively reducing hallucination and bias while maintaining pathological accuracy. The source code is available at https://github.com/meidandz/EAGLE. © 2025 Association for Computational Linguistics.

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.

Vision Language Models (VLMs) like CLIP have attracted substantial attention in pathology, serving as backbones for applications such as zero-shot image classification and Whole Slide Image (WSI) analysis. Additionally, they can function as vision encoders when combined with large language models (LLMs) to support broader capabilities. Current efforts to train pathology VLMs rely on pathology image-text pairs from platforms like PubMed, YouTube, and Twitter, which provide limited, unscalable data with generally suboptimal image quality. In this work, we leverage large-scale WSI datasets like TCGA to extract numerous high-quality image patches. We then train a large multimodal model (LMM) to generate captions for extracted images, creating PathGen-1.6M, a dataset containing 1.6 million high-quality image-caption pairs. Our approach involves multiple agent models collaborating to extract representative WSI patches, generating and refining captions to obtain high-quality image-text pairs. Extensive experiments show that integrating these generated pairs with existing datasets to train a pathology-specific CLIP model, PathGen-CLIP, significantly enhances its ability to analyze pathological images, with substantial improvements across nine pathology-related zero-shot image classification tasks and three whole-slide image tasks. Furthermore, we construct 200K instruction-tuning data based on PathGen-1.6M and integrate PathGen-CLIP with the Vicuna LLM to create more powerful multimodal models through instruction tuning. Overall, we provide a scalable pathway for high-quality data generation in pathology, paving the way for next-generation general pathology models. Our dataset, code, and model are open-access at https://github.com/PathFoundation/PathGen-1.6M.