Yizhi Wang

Xitong Ling, Minxi Ouyang, Yizhi Wang et al. · tsinghua

Histopathology analysis is the gold standard for medical diagnosis. Accurate classification of whole slide images (WSIs) and region-of-interests (ROIs) localization can assist pathologists in diagnosis. The gigapixel resolution of WSI and the absence of fine-grained annotations make direct classification and analysis challenging. In weakly supervised learning, multiple instance learning (MIL) presents a promising approach for WSI classification. The prevailing strategy is to use attention mechanisms to measure instance importance for classification. However, attention mechanisms fail to capture inter-instance information, and self-attention causes quadratic computational complexity. To address these challenges, we propose AMD-MIL, an agent aggregator with a mask denoise mechanism. The agent token acts as an intermediate variable between the query and key for computing instance importance. Mask and denoising matrices, mapped from agents-aggregated value, dynamically mask low-contribution representations and eliminate noise. AMD-MIL achieves better attention allocation by adjusting feature representations, capturing micro-metastases in cancer, and improving interpretability. Extensive experiments on CAMELYON-16, CAMELYON-17, TCGA-KIDNEY, and TCGA-LUNG show AMD-MIL's superiority over state-of-the-art methods.

Fang Yan, Jianfeng Wu, Jiawen Li et al.

The complexity and variability inherent in high-resolution pathological images present significant challenges in computational pathology. While pathology foundation models leveraging AI have catalyzed transformative advancements, their development demands large-scale datasets, considerable storage capacity, and substantial computational resources. Furthermore, ensuring their clinical applicability and generalizability requires rigorous validation across a broad spectrum of clinical tasks. Here, we present PathOrchestra, a versatile pathology foundation model trained via self-supervised learning on a dataset comprising 300K pathological slides from 20 tissue and organ types across multiple centers. The model was rigorously evaluated on 112 clinical tasks using a combination of 61 private and 51 public datasets. These tasks encompass digital slide preprocessing, pan-cancer classification, lesion identification, multi-cancer subtype classification, biomarker assessment, gene expression prediction, and the generation of structured reports. PathOrchestra demonstrated exceptional performance across 27,755 WSIs and 9,415,729 ROIs, achieving over 0.950 accuracy in 47 tasks, including pan-cancer classification across various organs, lymphoma subtype diagnosis, and bladder cancer screening. Notably, it is the first model to generate structured reports for high-incidence colorectal cancer and diagnostically complex lymphoma-areas that are infrequently addressed by foundational models but hold immense clinical potential. Overall, PathOrchestra exemplifies the feasibility and efficacy of a large-scale, self-supervised pathology foundation model, validated across a broad range of clinical-grade tasks. Its high accuracy and reduced reliance on extensive data annotation underline its potential for clinical integration, offering a pathway toward more efficient and high-quality medical services.

Weiming Chen, Xitong Ling, Xidong Wang et al.

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

Yizhi Wang, Li Chen, Qiang Huang et al.

Cervical cancer remains a major malignancy, necessitating extensive and complex histopathological assessments and comprehensive support tools. Although deep learning shows promise, these models still lack accuracy and generalizability. General foundation models offer a broader reach but remain limited in capturing subspecialty-specific features and task adaptability. We introduce the Cervical Subspecialty Pathology (CerS-Path) diagnostic system, developed through two synergistic pretraining stages: self-supervised learning on approximately 190 million tissue patches from 140,000 slides to build a cervical-specific feature extractor, and multimodal enhancement with 2.5 million image-text pairs, followed by integration with multiple downstream diagnostic functions. Supporting eight diagnostic functions, including rare cancer classification and multimodal Q&A, CerS-Path surpasses prior foundation models in scope and clinical applicability. Comprehensive evaluations demonstrate a significant advance in cervical pathology, with prospective testing on 3,173 cases across five centers maintaining 99.38% screening sensitivity and excellent generalizability, highlighting its potential for subspecialty diagnostic translation and cervical cancer screening.

Deshui Yu, Yizhi Wang, Saihui Jin et al.

Large language models (LLMs) excel on general tasks yet still hallucinate in high-barrier domains such as pathology. Prior work often relies on domain fine-tuning, which neither expands the knowledge boundary nor enforces evidence-grounded constraints. We therefore build a pathology vector database covering 28 subfields and 1.53 million paragraphs, and present YpathRAG, a pathology-oriented RAG framework with dual-channel hybrid retrieval (BGE-M3 dense retrieval coupled with vocabulary-guided sparse retrieval) and an LLM-based supportive-evidence judgment module that closes the retrieval-judgment-generation loop. We also release two evaluation benchmarks, YpathR and YpathQA-M. On YpathR, YpathRAG attains Recall@5 of 98.64%, a gain of 23 percentage points over the baseline; on YpathQA-M, a set of the 300 most challenging questions, it increases the accuracies of both general and medical LLMs by 9.0% on average and up to 15.6%. These results demonstrate improved retrieval quality and factual reliability, providing a scalable construction paradigm and interpretable evaluation for pathology-oriented RAG.

Xitong Ling, Yifeng Ping, Jiawen Li et al.

Multiple Instance Learning (MIL) plays a significant role in computational pathology, enabling weakly supervised analysis of Whole Slide Image (WSI) datasets. The field of WSI analysis is confronted with a severe long-tailed distribution problem, which significantly impacts the performance of classifiers. Long-tailed distributions lead to class imbalance, where some classes have sparse samples while others are abundant, making it difficult for classifiers to accurately identify minority class samples. To address this issue, we propose an ensemble learning method based on MIL, which employs expert decoders with shared aggregators and consistency constraints to learn diverse distributions and reduce the impact of class imbalance on classifier performance. Moreover, we introduce a multimodal distillation framework that leverages text encoders pre-trained on pathology-text pairs to distill knowledge and guide the MIL aggregator in capturing stronger semantic features relevant to class information. To ensure flexibility, we use learnable prompts to guide the distillation process of the pre-trained text encoder, avoiding limitations imposed by specific prompts. Our method, MDE-MIL, integrates multiple expert branches focusing on specific data distributions to address long-tailed issues. Consistency control ensures generalization across classes. Multimodal distillation enhances feature extraction. Experiments on Camelyon+-LT and PANDA-LT datasets show it outperforms state-of-the-art methods.