Generative AI for Misalignment-Resistant Virtual Staining to Accelerate Histopathology Workflows

Accurate histopathological diagnosis often requires multiple differently stained tissue sections, a process that is time-consuming, labor-intensive, and environmentally taxing due to the use of multiple chemical stains. Recently, virtual staining has emerged as a promising alternative that is faster, tissue-conserving, and environmentally friendly. However, existing virtual staining methods face significant challenges in clinical applications, primarily due to their reliance on well-aligned paired data. Obtaining such data is inherently difficult because chemical staining processes can distort tissue structures, and a single tissue section cannot undergo multiple staining procedures without damage or loss of information. As a result, most available virtual staining datasets are either unpaired or roughly paired, making it difficult for existing methods to achieve accurate pixel-level supervision. To address this challenge, we propose a robust virtual staining framework featuring cascaded registration mechanisms to resolve spatial mismatches between generated outputs and their corresponding ground truth. Experimental results demonstrate that our method significantly outperforms state-of-the-art models across five datasets, achieving an average improvement of 3.2% on internal datasets and 10.1% on external datasets. Moreover, in datasets with substantial misalignment, our approach achieves a remarkable 23.8% improvement in peak signal-to-noise ratio compared to baseline models. The exceptional robustness of the proposed method across diverse datasets simplifies the data acquisition process for virtual staining and offers new insights for advancing its development.

A Versatile Pathology Co-pilot via Reasoning Enhanced Multimodal Large Language Model

Multimodal large language models (MLLMs) have emerged as powerful tools for computational pathology, offering unprecedented opportunities to integrate pathological images with language context for comprehensive diagnostic analysis. These models hold particular promise for automating complex tasks that traditionally require expert interpretation of pathologists. However, current MLLM approaches in pathology demonstrate significantly constrained reasoning capabilities, primarily due to their reliance on expensive chain-of-thought annotations. Additionally, existing methods remain limited to simplex application of visual question answering (VQA) at region-of-interest (ROI) level, failing to address the full spectrum of diagnostic needs such as ROI classification, detection, segmentation, whole-slide-image (WSI) classification and VQA in clinical practice. In this study, we present SmartPath-R1, a versatile MLLM capable of simultaneously addressing both ROI-level and WSI-level tasks while demonstrating robust pathological reasoning capability. Our framework combines scale-dependent supervised fine-tuning and task-aware reinforcement fine-tuning, which circumvents the requirement for chain-of-thought supervision by leveraging the intrinsic knowledge within MLLM. Furthermore, SmartPath-R1 integrates multiscale and multitask analysis through a mixture-of-experts mechanism, enabling dynamic processing for diverse tasks. We curate a large-scale dataset comprising 2.3M ROI samples and 188K WSI samples for training and evaluation. Extensive experiments across 72 tasks validate the effectiveness and superiority of the proposed approach. This work represents a significant step toward developing versatile, reasoning-enhanced AI systems for precision pathology.

Segment Anything in Pathology Images with Natural Language

Pathology image segmentation is crucial in computational pathology for analyzing histological features relevant to cancer diagnosis and prognosis. However, current methods face major challenges in clinical applications due to limited annotated data and restricted category definitions. To address these limitations, we propose PathSegmentor, the first text-prompted segmentation foundation model designed specifically for pathology images. We also introduce PathSeg , the largest and most comprehensive dataset for pathology segmentation, built from 17 public sources and containing 275k image-mask-label triples across 160 diverse categories. With PathSegmentor, users can perform semantic segmentation using natural language prompts, eliminating the need for laborious spatial inputs such as points or boxes. Extensive experiments demonstrate that PathSegmentor outperforms specialized models with higher accuracy and broader applicability, while maintaining a compact architecture. It significantly surpasses existing spatial- and text-prompted models by 0.145 and 0.429 in overall Dice scores, respectively, showing strong robustness in segmenting complex structures and generalizing to external datasets. Moreover, PathSegmentor's outputs enhance the interpretability of diagnostic models through feature importance estimation and imaging biomarker discovery, offering pathologists evidence-based support for clinical decision-making. This work advances the development of explainable AI in precision oncology.

PathBench: A comprehensive comparison benchmark for pathology foundation models towards precision oncology

The emergence of pathology foundation models has revolutionized computational histopathology, enabling highly accurate, generalized whole-slide image analysis for improved cancer diagnosis, and prognosis assessment. While these models show remarkable potential across cancer diagnostics and prognostics, their clinical translation faces critical challenges including variability in optimal model across cancer types, potential data leakage in evaluation, and lack of standardized benchmarks. Without rigorous, unbiased evaluation, even the most advanced PFMs risk remaining confined to research settings, delaying their life-saving applications. Existing benchmarking efforts remain limited by narrow cancer-type focus, potential pretraining data overlaps, or incomplete task coverage. We present PathBench, the first comprehensive benchmark addressing these gaps through: multi-center in-hourse datasets spanning common cancers with rigorous leakage prevention, evaluation across the full clinical spectrum from diagnosis to prognosis, and an automated leaderboard system for continuous model assessment. Our framework incorporates large-scale data, enabling objective comparison of PFMs while reflecting real-world clinical complexity. All evaluation data comes from private medical providers, with strict exclusion of any pretraining usage to avoid data leakage risks. We have collected 15,888 WSIs from 8,549 patients across 10 hospitals, encompassing over 64 diagnosis and prognosis tasks. Currently, our evaluation of 19 PFMs shows that Virchow2 and H-Optimus-1 are the most effective models overall. This work provides researchers with a robust platform for model development and offers clinicians actionable insights into PFM performance across diverse clinical scenarios, ultimately accelerating the translation of these transformative technologies into routine pathology practice.

Towards A Generalizable Pathology Foundation Model via Unified Knowledge Distillation

Foundation models pretrained on large-scale datasets are revolutionizing the field of computational pathology (CPath). The generalization ability of foundation models is crucial for the success in various downstream clinical tasks. However, current foundation models have only been evaluated on a limited type and number of tasks, leaving their generalization ability and overall performance unclear. To address this gap, we established a most comprehensive benchmark to evaluate the performance of off-the-shelf foundation models across six distinct clinical task types, encompassing a total of 39 specific tasks. Our findings reveal that existing foundation models excel at certain task types but struggle to effectively handle the full breadth of clinical tasks. To improve the generalization of pathology foundation models, we propose a unified knowledge distillation framework consisting of both expert and self knowledge distillation, where the former allows the model to learn from the knowledge of multiple expert models, while the latter leverages self-distillation to enable image representation learning via local-global alignment. Based on this framework, a Generalizable Pathology Foundation Model (GPFM) is pretrained on a large-scale dataset consisting of 190 million images from around 86,000 public H\&E whole slides across 34 major tissue types. Evaluated on the established benchmark, GPFM achieves an impressive average rank of 1.36, with 29 tasks ranked 1st, while the the second-best model, UNI, attains an average rank of 2.96, with only 4 tasks ranked 1st. The superior generalization of GPFM demonstrates its exceptional modeling capabilities across a wide range of clinical tasks, positioning it as a new cornerstone for feature representation in CPath.

A Multimodal Knowledge-enhanced Whole-slide Pathology Foundation Model

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or vision-captions data, disregarding invaluable pathology reports and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Here we curated the largest multimodal dataset consisting of H\&E diagnostic whole slide images and their associated pathology reports and RNA-Seq data, resulting in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm which injects multimodal knowledge at the whole-slide context into the pathology FM, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the workflow of pretraining for CPath, which enables the pathology FM to acquire the whole-slide context. To our knowledge, this is the first attempt to incorporate multimodal knowledge at the slide level for enhancing pathology FMs, expanding the modelling context from unimodal to multimodal knowledge and from patch-level to slide-level. To systematically evaluate the capabilities of mSTAR, extensive experiments including slide-level unimodal and multimodal applications, are conducted across 7 diverse types of tasks on 43 subtasks, resulting in the largest spectrum of downstream tasks. The average performance in various slide-level applications consistently demonstrates significant performance enhancements for mSTAR compared to SOTA FMs.