Daily Papers

Sparse autoencoders (SAEs) emerged as a promising tool for mechanistic interpretability of transformer-based foundation models. Very recently, SAEs were also adopted for the visual domain, enabling the discovery of visual concepts and their patch-wise attribution to tokens in the transformer model. While a growing number of foundation models emerged for medical imaging, tools for explaining their inferences are still lacking. In this work, we show the applicability of SAEs for hematology. We propose CytoSAE, a sparse autoencoder which is trained on over 40,000 peripheral blood single-cell images. CytoSAE generalizes to diverse and out-of-domain datasets, including bone marrow cytology, where it identifies morphologically relevant concepts which we validated with medical experts. Furthermore, we demonstrate scenarios in which CytoSAE can generate patient-specific and disease-specific concepts, enabling the detection of pathognomonic cells and localized cellular abnormalities at the patch level. We quantified the effect of concepts on a patient-level AML subtype classification task and show that CytoSAE concepts reach performance comparable to the state-of-the-art, while offering explainability on the sub-cellular level. Source code and model weights are available at https://github.com/dynamical-inference/cytosae.

Deep learning based automated pathological diagnosis has markedly improved diagnostic efficiency and reduced variability between observers, yet its clinical adoption remains limited by opaque model decisions and a lack of traceable rationale. To address this, recent multimodal visual reasoning architectures provide a unified framework that generates segmentation masks at the pixel level alongside semantically aligned textual explanations. By localizing lesion regions and producing expert style diagnostic narratives, these models deliver the transparent and interpretable insights necessary for dependable AI assisted pathology. Building on these advancements, we propose PathMR, a cell-level Multimodal visual Reasoning framework for Pathological image analysis. Given a pathological image and a textual query, PathMR generates expert-level diagnostic explanations while simultaneously predicting cell distribution patterns. To benchmark its performance, we evaluated our approach on the publicly available PathGen dataset as well as on our newly developed GADVR dataset. Extensive experiments on these two datasets demonstrate that PathMR consistently outperforms state-of-the-art visual reasoning methods in text generation quality, segmentation accuracy, and cross-modal alignment. These results highlight the potential of PathMR for improving interpretability in AI-driven pathological diagnosis. The code will be publicly available in https://github.com/zhangye-zoe/PathMR.

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.

Recent advances in vision language models (VLMs) have enabled broad progress in the general medical field. However, pathology still remains a more challenging subdomain, with current pathology specific VLMs exhibiting limitations in both diagnostic accuracy and reasoning plausibility. Such shortcomings are largely attributable to the nature of current pathology datasets, which are primarily composed of image description pairs that lack the depth and structured diagnostic paradigms employed by real world pathologists. In this study, we leverage pathology textbooks and real world pathology experts to construct high-quality, reasoning-oriented datasets. Building on this, we introduce Patho-R1, a multimodal RL-based pathology Reasoner, trained through a three-stage pipeline: (1) continued pretraining on 3.5 million image-text pairs for knowledge infusion; (2) supervised fine-tuning on 500k high-quality Chain-of-Thought samples for reasoning incentivizing; (3) reinforcement learning using Group Relative Policy Optimization and Decoupled Clip and Dynamic sAmpling Policy Optimization strategies for multimodal reasoning quality refinement. To further assess the alignment quality of our dataset, we propose PathoCLIP, trained on the same figure-caption corpus used for continued pretraining. Comprehensive experimental results demonstrate that both PathoCLIP and Patho-R1 achieve robust performance across a wide range of pathology-related tasks, including zero-shot classification, cross-modal retrieval, Visual Question Answering, and Multiple Choice Question. Our project is available at the Patho-R1 repository: https://github.com/Wenchuan-Zhang/Patho-R1.

With the rapid development of computational pathology, many AI-assisted diagnostic tasks have emerged. Cellular nuclei segmentation can segment various types of cells for downstream analysis, but it relies on predefined categories and lacks flexibility. Moreover, pathology visual question answering can perform image-level understanding but lacks region-level detection capability. To address this, we propose a new benchmark called Pathology Visual Grounding (PathVG), which aims to detect regions based on expressions with different attributes. To evaluate PathVG, we create a new dataset named RefPath which contains 27,610 images with 33,500 language-grounded boxes. Compared to visual grounding in other domains, PathVG presents pathological images at multi-scale and contains expressions with pathological knowledge. In the experimental study, we found that the biggest challenge was the implicit information underlying the pathological expressions. Based on this, we proposed Pathology Knowledge-enhanced Network (PKNet) as the baseline model for PathVG. PKNet leverages the knowledge-enhancement capabilities of Large Language Models (LLMs) to convert pathological terms with implicit information into explicit visual features, and fuses knowledge features with expression features through the designed Knowledge Fusion Module (KFM). The proposed method achieves state-of-the-art performance on the PathVG benchmark.

This paper presents a Patherea, a framework for point-based cell detection and classification that provides a complete solution for developing and evaluating state-of-the-art approaches. We introduce a large-scale dataset collected to directly replicate a clinical workflow for Ki-67 proliferation index estimation and use it to develop an efficient point-based approach that directly predicts point-based predictions, without the need for intermediate representations. The proposed approach effectively utilizes point proposal candidates with the hybrid Hungarian matching strategy and a flexible architecture that enables the usage of various backbones and (pre)training strategies. We report state-of-the-art results on existing public datasets - Lizard, BRCA-M2C, BCData, and the newly proposed Patherea dataset. We show that the performance on existing public datasets is saturated and that the newly proposed Patherea dataset represents a significantly harder challenge for the recently proposed approaches. We also demonstrate the effectiveness of recently proposed pathology foundational models that our proposed approach can natively utilize and benefit from. We also revisit the evaluation protocol that is used in the broader field of cell detection and classification and identify the erroneous calculation of performance metrics. Patherea provides a benchmarking utility that addresses the identified issues and enables a fair comparison of different approaches. The dataset and the code will be publicly released upon acceptance.

As advances in large language models (LLMs) and multimodal techniques continue to mature, the development of general-purpose multimodal large language models (MLLMs) has surged, offering significant applications in interpreting natural images. However, the field of pathology has largely remained untapped, particularly in gathering high-quality data and designing comprehensive model frameworks. To bridge the gap in pathology MLLMs, we present PathAsst, a multimodal generative foundation AI assistant to revolutionize diagnostic and predictive analytics in pathology. The development of PathAsst involves three pivotal steps: data acquisition, CLIP model adaptation, and the training of PathAsst's multimodal generative capabilities. Firstly, we collect over 207K high-quality pathology image-text pairs from authoritative sources. Leveraging the advanced power of ChatGPT, we generate over 180K instruction-following samples. Furthermore, we devise additional instruction-following data specifically tailored for invoking eight pathology-specific sub-models we prepared, allowing the PathAsst to effectively collaborate with these models, enhancing its diagnostic ability. Secondly, by leveraging the collected data, we construct PathCLIP, a pathology-dedicated CLIP, to enhance PathAsst's capabilities in interpreting pathology images. Finally, we integrate PathCLIP with the Vicuna-13b and utilize pathology-specific instruction-tuning data to enhance the multimodal generation capacity of PathAsst and bolster its synergistic interactions with sub-models. The experimental results of PathAsst show the potential of harnessing AI-powered generative foundation model to improve pathology diagnosis and treatment processes.

Nasal Cytology is a new and efficient clinical technique to diagnose rhinitis and allergies that is not much widespread due to the time-consuming nature of cell counting; that is why AI-aided counting could be a turning point for the diffusion of this technique. In this article we present the first dataset of rhino-cytological field images: the NCD (Nasal Cytology Dataset), aimed to train and deploy Object Detection models to support physicians and biologists during clinical practice. The real distribution of the cytotypes, populating the nasal mucosa has been replicated, sampling images from slides of clinical patients, and manually annotating each cell found on them. The correspondent object detection task presents non'trivial issues associated with the strong class imbalancement, involving the rarest cell types. This work contributes to some of open challenges by presenting a novel machine learning-based approach to aid the automated detection and classification of nasal mucosa cells: the DETR and YOLO models shown good performance in detecting cells and classifying them correctly, revealing great potential to accelerate the work of rhinology experts.

Multiplex immunofluorescence and immunohistochemistry benefit patients by allowing cancer pathologists to identify several proteins expressed on the surface of cells, enabling cell classification, better understanding of the tumour micro-environment, more accurate diagnoses, prognoses, and tailored immunotherapy based on the immune status of individual patients. However, they are expensive and time consuming processes which require complex staining and imaging techniques by expert technicians. Hoechst staining is much cheaper and easier to perform, but is not typically used in this case as it binds to DNA rather than to the proteins targeted by immunofluorescent techniques, and it was not previously thought possible to differentiate cells expressing these proteins based only on DNA morphology. In this work we show otherwise, training a deep convolutional neural network to identify cells expressing three proteins (T lymphocyte markers CD3 and CD8, and the B lymphocyte marker CD20) with greater than 90% precision and recall, from Hoechst 33342 stained tissue only. Our model learns previously unknown morphological features associated with expression of these proteins which can be used to accurately differentiate lymphocyte subtypes for use in key prognostic metrics such as assessment of immune cell infiltration,and thereby predict and improve patient outcomes without the need for costly multiplex immunofluorescence.

Although Vision Language Models (VLMs) have shown strong generalization in medical imaging, pathology presents unique challenges due to ultra-high resolution, complex tissue structures, and nuanced clinical semantics. These factors make pathology VLMs prone to hallucinations, i.e., generating outputs inconsistent with visual evidence, which undermines clinical trust. Existing RAG approaches in this domain largely depend on text-based knowledge bases, limiting their ability to leverage diagnostic visual cues. To address this, we propose Patho-AgenticRAG, a multimodal RAG framework with a database built on page-level embeddings from authoritative pathology textbooks. Unlike traditional text-only retrieval systems, it supports joint text-image search, enabling direct retrieval of textbook pages that contain both the queried text and relevant visual cues, thus avoiding the loss of critical image-based information. Patho-AgenticRAG also supports reasoning, task decomposition, and multi-turn search interactions, improving accuracy in complex diagnostic scenarios. Experiments show that Patho-AgenticRAG significantly outperforms existing multimodal models in complex pathology tasks like multiple-choice diagnosis and visual question answering. Our project is available at the Patho-AgenticRAG repository: https://github.com/Wenchuan-Zhang/Patho-AgenticRAG.

Digital pathology enables automatic analysis of histopathological sections using artificial intelligence (AI). Automatic evaluation could improve diagnostic efficiency and help find associations between morphological features and clinical outcome. For development of such prediction models, identifying invasive epithelial cells, and separating these from benign epithelial cells and in situ lesions would be the first step. In this study, we aimed to develop an AI model for segmentation of epithelial cells in sections from breast cancer. We generated epithelial ground truth masks by restaining hematoxylin and eosin (HE) sections with cytokeratin (CK) AE1/AE3, and by pathologists' annotations. HE/CK image pairs were used to train a convolutional neural network, and data augmentation was used to make the model more robust. Tissue microarrays (TMAs) from 839 patients, and whole slide images from two patients were used for training and evaluation of the models. The sections were derived from four cohorts of breast cancer patients. TMAs from 21 patients from a fifth cohort was used as a second test set. In quantitative evaluation, a mean Dice score of 0.70, 0.79, and 0.75 for invasive epithelial cells, benign epithelial cells, and in situ lesions, respectively, were achieved. In qualitative scoring (0-5) by pathologists, results were best for all epithelium and invasive epithelium, with scores of 4.7 and 4.4. Scores for benign epithelium and in situ lesions were 3.7 and 2.0. The proposed model segmented epithelial cells in HE stained breast cancer slides well, but further work is needed for accurate division between the classes. Immunohistochemistry, together with pathologists' annotations, enabled the creation of accurate ground truths. The model is made freely available in FastPathology and the code is available at https://github.com/AICAN-Research/breast-epithelium-segmentation

High-content screening (HCS) assays based on high-throughput microscopy techniques such as Cell Painting have enabled the interrogation of cells' morphological responses to perturbations at an unprecedented scale. The collection of such data promises to facilitate a better understanding of the relationships between different perturbations and their effects on cellular state. Towards achieving this goal, recent advances in cross-modal contrastive learning could, in theory, be leveraged to learn a unified latent space that aligns perturbations with their corresponding morphological effects. However, the application of such methods to HCS data is not straightforward due to substantial differences in the semantics of Cell Painting images compared to natural images, and the difficulty of representing different classes of perturbations (e.g., small molecule vs CRISPR gene knockout) in a single latent space. In response to these challenges, here we introduce CellCLIP, a cross-modal contrastive learning framework for HCS data. CellCLIP leverages pre-trained image encoders coupled with a novel channel encoding scheme to better capture relationships between different microscopy channels in image embeddings, along with natural language encoders for representing perturbations. Our framework outperforms current open-source models, demonstrating the best performance in both cross-modal retrieval and biologically meaningful downstream tasks while also achieving significant reductions in computation time.

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 to generate captions for these 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.

Complex cell signaling systems -- governed by varying protein abundances and interactions -- generate diverse cell types across organs. These systems evolve under influences such as age, sex, diet, environmental exposures, and diseases, making them challenging to decode given the involvement of tens of thousands of genes and proteins. Recently, hundreds of millions of single-cell omics data have provided a robust foundation for understanding these signaling networks within various cell subpopulations and conditions. Inspired by the success of large foundation models (for example, large language models and large vision models) pre-trained on massive datasets, we introduce OmniCellTOSG, the first dataset of cell text-omic signaling graphs (TOSGs). Each TOSG represents the signaling network of an individual or meta-cell and is labeled with information such as organ, disease, sex, age, and cell subtype. OmniCellTOSG offers two key contributions. First, it introduces a novel graph model that integrates human-readable annotations -- such as biological functions, cellular locations, signaling pathways, related diseases, and drugs -- with quantitative gene and protein abundance data, enabling graph reasoning to decode cell signaling. This approach calls for new joint models combining large language models and graph neural networks. Second, the dataset is built from single-cell RNA sequencing data of approximately 120 million cells from diverse tissues and conditions (healthy and diseased) and is fully compatible with PyTorch. This facilitates the development of innovative cell signaling models that could transform research in life sciences, healthcare, and precision medicine. The OmniCellTOSG dataset is continuously expanding and will be updated regularly. The dataset and code are available at https://github.com/FuhaiLiAiLab/OmniCellTOSG.

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 image-caption data, disregarding pathology reports with more clinically authentic information from pathologists 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. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

Mitotic figure (MF) detection in histopathology images is challenging due to large variations in slide scanners, staining protocols, tissue types, and the presence of artifacts. This paper presents a collection of training techniques - a bag of tricks - that enable robust, real-time MF detection across diverse domains. We build on the efficient RTMDet single stage object detector to achieve high inference speed suitable for clinical deployment. Our method addresses scanner variability and tumor heterogeneity via extensive multi-domain training data, balanced sampling, and careful augmentation. Additionally, we employ targeted, hard negative mining on necrotic and debris tissue to reduce false positives. In a grouped 5-fold cross-validation across multiple MF datasets, our model achieves an F1 score between 0.78 and 0.84. On the preliminary test set of the MItosis DOmain Generalization (MIDOG) 2025 challenge, our single-stage RTMDet-S based approach reaches an F1 of 0.81, outperforming larger models and demonstrating adaptability to new, unfamiliar domains. The proposed solution offers a practical trade-off between accuracy and speed, making it attractive for real-world clinical adoption.

Advancing AI in computational pathology requires large, high-quality, and diverse datasets, yet existing public datasets are often limited in organ diversity, class coverage, or annotation quality. To bridge this gap, we introduce SPIDER (Supervised Pathology Image-DEscription Repository), the largest publicly available patch-level dataset covering multiple organ types, including Skin, Colorectal, and Thorax, with comprehensive class coverage for each organ. SPIDER provides high-quality annotations verified by expert pathologists and includes surrounding context patches, which enhance classification performance by providing spatial context. Alongside the dataset, we present baseline models trained on SPIDER using the Hibou-L foundation model as a feature extractor combined with an attention-based classification head. The models achieve state-of-the-art performance across multiple tissue categories and serve as strong benchmarks for future digital pathology research. Beyond patch classification, the model enables rapid identification of significant areas, quantitative tissue metrics, and establishes a foundation for multimodal approaches. Both the dataset and trained models are publicly available to advance research, reproducibility, and AI-driven pathology development. Access them at: https://github.com/HistAI/SPIDER

Histopathological analysis is a cornerstone of cancer diagnosis, with Hematoxylin and Eosin (H&E) staining routinely acquired for every patient to visualize cell morphology and tissue architecture. On the other hand, multiplex immunofluorescence (mIF) enables more precise cell type identification via proteomic markers, but has yet to achieve widespread clinical adoption due to cost and logistical constraints. To bridge this gap, we introduce MIPHEI (Multiplex Immunofluorescence Prediction from H&E), a U-Net-inspired architecture that integrates state-of-the-art ViT foundation models as encoders to predict mIF signals from H&E images. MIPHEI targets a comprehensive panel of markers spanning nuclear content, immune lineages (T cells, B cells, myeloid), epithelium, stroma, vasculature, and proliferation. We train our model using the publicly available ORION dataset of restained H&E and mIF images from colorectal cancer tissue, and validate it on two independent datasets. MIPHEI achieves accurate cell-type classification from H&E alone, with F1 scores of 0.88 for Pan-CK, 0.57 for CD3e, 0.56 for SMA, 0.36 for CD68, and 0.30 for CD20, substantially outperforming both a state-of-the-art baseline and a random classifier for most markers. Our results indicate that our model effectively captures the complex relationships between nuclear morphologies in their tissue context, as visible in H&E images and molecular markers defining specific cell types. MIPHEI offers a promising step toward enabling cell-type-aware analysis of large-scale H&E datasets, in view of uncovering relationships between spatial cellular organization and patient outcomes.

While pathology foundation models have transformed cancer image analysis, they often lack integration with molecular data at single-cell resolution, limiting their utility for precision oncology. Here, we present PAST, a pan-cancer single-cell foundation model trained on 20 million paired histopathology images and single-cell transcriptomes spanning multiple tumor types and tissue contexts. By jointly encoding cellular morphology and gene expression, PAST learns unified cross-modal representations that capture both spatial and molecular heterogeneity at the cellular level. This approach enables accurate prediction of single-cell gene expression, virtual molecular staining, and multimodal survival analysis directly from routine pathology slides. Across diverse cancers and downstream tasks, PAST consistently exceeds the performance of existing approaches, demonstrating robust generalizability and scalability. Our work establishes a new paradigm for pathology foundation models, providing a versatile tool for high-resolution spatial omics, mechanistic discovery, and precision cancer research.

Millions of melanocytic skin lesions are examined by pathologists each year, the majority of which concern common nevi (i.e., ordinary moles). While most of these lesions can be diagnosed in seconds, writing the corresponding pathology report is much more time-consuming. Automating part of the report writing could, therefore, alleviate the increasing workload of pathologists. In this work, we develop a vision-language model specifically for the pathology domain of cutaneous melanocytic lesions. The model follows the Contrastive Captioner framework and was trained and evaluated using a melanocytic lesion dataset of 42,512 H&E-stained whole slide images and 19,645 corresponding pathology reports. Our results show that the quality scores of model-generated reports were on par with pathologist-written reports for common nevi, assessed by an expert pathologist in a reader study. While report generation revealed to be more difficult for rare melanocytic lesion subtypes, the cross-modal retrieval performance for these cases was considerably better.

Identifying cell types and understanding their functional properties is crucial for unraveling the mechanisms underlying perception and cognition. In the retina, functional types can be identified by carefully selected stimuli, but this requires expert domain knowledge and biases the procedure towards previously known cell types. In the visual cortex, it is still unknown what functional types exist and how to identify them. Thus, for unbiased identification of the functional cell types in retina and visual cortex, new approaches are needed. Here we propose an optimization-based clustering approach using deep predictive models to obtain functional clusters of neurons using Most Discriminative Stimuli (MDS). Our approach alternates between stimulus optimization with cluster reassignment akin to an expectation-maximization algorithm. The algorithm recovers functional clusters in mouse retina, marmoset retina and macaque visual area V4. This demonstrates that our approach can successfully find discriminative stimuli across species, stages of the visual system and recording techniques. The resulting most discriminative stimuli can be used to assign functional cell types fast and on the fly, without the need to train complex predictive models or show a large natural scene dataset, paving the way for experiments that were previously limited by experimental time. Crucially, MDS are interpretable: they visualize the distinctive stimulus patterns that most unambiguously identify a specific type of neuron.

Rapid progress in computational pathology is increasingly driven by vision foundation models pretrained on vast histopathology datasets. While recent efforts have prioritized training on an ever-larger amount of patches, we take an alternative approach focused on data diversity. Our foundation model, Athena, was initialized from a pretrained model and trained on just 115 million tissue patches, several times fewer than recent histopathology foundation models. Rather than relying on patch volume or complex sampling heuristics, we maximize data diversity by randomly selecting only a moderate number of patches per whole-slide image from our diverse internal repository, which spans multiple countries, institutions, and scanner types. Evaluated on a single patch-level benchmark and four slide-level downstream tasks (two molecular and two morphological), Athena approaches the state-of-the-art and even surpasses several models trained on substantially larger datasets. This indicates that diversity across whole-slide images, rather than patch quantity alone, drives learning in histopathology foundation models.

Masked image modelling (MIM) is a powerful self-supervised representation learning paradigm, whose potential has not been widely demonstrated in medical image analysis. In this work, we show the capacity of MIM to capture rich semantic representations of Haemotoxylin & Eosin (H&E)-stained images at the nuclear level. Inspired by Bidirectional Encoder representation from Image Transformers (BEiT), we split the images into smaller patches and generate corresponding discrete visual tokens. In addition to the regular grid-based patches, typically used in visual Transformers, we introduce patches of individual cell nuclei. We propose positional encoding of the irregular distribution of these structures within an image. We pre-train the model in a self-supervised manner on H&E-stained whole-slide images of diffuse large B-cell lymphoma, where cell nuclei have been segmented. The pre-training objective is to recover the original discrete visual tokens of the masked image on the one hand, and to reconstruct the visual tokens of the masked object instances on the other. Coupling these two pre-training tasks allows us to build powerful, context-aware representations of nuclei. Our model generalizes well and can be fine-tuned on downstream classification tasks, achieving improved cell classification accuracy on PanNuke dataset by more than 5% compared to current instance segmentation methods.

Breast cancer survival prediction in computational pathology presents a remarkable challenge due to tumor heterogeneity. For instance, different regions of the same tumor in the pathology image can show distinct morphological and molecular characteristics. This makes it difficult to extract representative features from whole slide images (WSIs) that truly reflect the tumor's aggressive potential and likely survival outcomes. In this paper, we present PathoHR, a novel pipeline for accurate breast cancer survival prediction that enhances any size of pathological images to enable more effective feature learning. Our approach entails (1) the incorporation of a plug-and-play high-resolution Vision Transformer (ViT) to enhance patch-wise WSI representation, enabling more detailed and comprehensive feature extraction, (2) the systematic evaluation of multiple advanced similarity metrics for comparing WSI-extracted features, optimizing the representation learning process to better capture tumor characteristics, (3) the demonstration that smaller image patches enhanced follow the proposed pipeline can achieve equivalent or superior prediction accuracy compared to raw larger patches, while significantly reducing computational overhead. Experimental findings valid that PathoHR provides the potential way of integrating enhanced image resolution with optimized feature learning to advance computational pathology, offering a promising direction for more accurate and efficient breast cancer survival prediction. Code will be available at https://github.com/AIGeeksGroup/PathoHR.

Cell instance segmentation in cytology images has significant importance for biology analysis and cancer screening, while remains challenging due to 1) the extensive overlapping translucent cell clusters that cause the ambiguous boundaries, and 2) the confusion of mimics and debris as nuclei. In this work, we proposed a De-overlapping Network (DoNet) in a decompose-and-recombined strategy. A Dual-path Region Segmentation Module (DRM) explicitly decomposes the cell clusters into intersection and complement regions, followed by a Semantic Consistency-guided Recombination Module (CRM) for integration. To further introduce the containment relationship of the nucleus in the cytoplasm, we design a Mask-guided Region Proposal Strategy (MRP) that integrates the cell attention maps for inner-cell instance prediction. We validate the proposed approach on ISBI2014 and CPS datasets. Experiments show that our proposed DoNet significantly outperforms other state-of-the-art (SOTA) cell instance segmentation methods. The code is available at https://github.com/DeepDoNet/DoNet.

The accelerated adoption of digital pathology and advances in deep learning have enabled the development of powerful models for various pathology tasks across a diverse array of diseases and patient cohorts. However, model training is often difficult due to label scarcity in the medical domain and the model's usage is limited by the specific task and disease for which it is trained. Additionally, most models in histopathology leverage only image data, a stark contrast to how humans teach each other and reason about histopathologic entities. We introduce CONtrastive learning from Captions for Histopathology (CONCH), a visual-language foundation model developed using diverse sources of histopathology images, biomedical text, and notably over 1.17 million image-caption pairs via task-agnostic pretraining. Evaluated on a suite of 13 diverse benchmarks, CONCH can be transferred to a wide range of downstream tasks involving either or both histopathology images and text, achieving state-of-the-art performance on histology image classification, segmentation, captioning, text-to-image and image-to-text retrieval. CONCH represents a substantial leap over concurrent visual-language pretrained systems for histopathology, with the potential to directly facilitate a wide array of machine learning-based workflows requiring minimal or no further supervised fine-tuning.

Diagnosing a whole-slide image is an interactive, multi-stage process involving changes in magnification and movement between fields. Although recent pathology foundation models are strong, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. The blocker is data: scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not written in textbooks or online, and therefore absent from large language model training. We introduce the AI Session Recorder, which works with standard WSI viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands (inspect or peek at discrete magnifications) and bounding boxes. A lightweight human-in-the-loop review turns AI-drafted rationales into the Pathology-CoT dataset, a form of paired "where to look" and "why it matters" supervision produced at roughly six times lower labeling time. Using this behavioral data, we build Pathologist-o3, a two-stage agent that first proposes regions of interest and then performs behavior-guided reasoning. On gastrointestinal lymph-node metastasis detection, it achieved 84.5% precision, 100.0% recall, and 75.4% accuracy, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, this constitutes one of the first behavior-grounded agentic systems in pathology. Turning everyday viewer logs into scalable, expert-validated supervision, our framework makes agentic pathology practical and establishes a path to human-aligned, upgradeable clinical AI.

Histopathology and transcriptomics are fundamental modalities in oncology, encapsulating the morphological and molecular aspects of the disease. Multi-modal self-supervised learning has demonstrated remarkable potential in learning pathological representations by integrating diverse data sources. Conventional multi-modal integration methods primarily emphasize modality alignment, while paying insufficient attention to retaining the modality-specific structures. However, unlike conventional scenarios where multi-modal inputs share highly overlapping features, histopathology and transcriptomics exhibit pronounced heterogeneity, offering orthogonal yet complementary insights. Histopathology provides morphological and spatial context, elucidating tissue architecture and cellular topology, whereas transcriptomics delineates molecular signatures through gene expression patterns. This inherent disparity introduces a major challenge in aligning them while maintaining modality-specific fidelity. To address these challenges, we present MIRROR, a novel multi-modal representation learning method designed to foster both modality alignment and retention. MIRROR employs dedicated encoders to extract comprehensive features for each modality, which is further complemented by a modality alignment module to achieve seamless integration between phenotype patterns and molecular profiles. Furthermore, a modality retention module safeguards unique attributes from each modality, while a style clustering module mitigates redundancy and enhances disease-relevant information by modeling and aligning consistent pathological signatures within a clustering space. Extensive evaluations on TCGA cohorts for cancer subtyping and survival analysis highlight MIRROR's superior performance, demonstrating its effectiveness in constructing comprehensive oncological feature representations and benefiting the cancer diagnosis.

Background: Two strains of the endoparasitoid Cotesia typhae present a differential parasitism success on the host, Sesamia nonagrioides. One is virulent on both permissive and resistant host populations, and the other only on the permissive host. This interaction provides a very interesting frame for studying virulence factors. Here, we used a combination of comparative transcriptomic and proteomic analyses to unravel the molecular basis underlying virulence differences between the strains.Results: First, we report that virulence genes are mostly expressed during the nymphal stage of the parasitoid. Especially, proviral genes are broadly up-regulated at this stage, while their expression is only expected in the host. Parasitoid gene expression in the host increases with time, indicating the production of more virulence factors. Secondly, comparison between strains reveals differences in venom composition, with 12 proteins showing differential abundance. Proviral expression in the host displays a strong temporal variability, along with differential patterns between strains. Notably, a subset of proviral genes including protein-tyrosine phosphatases is specifically over-expressed in the resistant host parasitized by the less virulent strain, 24 hours after parasitism. This result particularly hints at host modulation of proviral expression.Conclusions: This study sheds light on the temporal expression of virulence factors of Cotesia typhae, both in the host and in the parasitoid. It also identifies potential molecular candidates driving differences in parasitism success between two strains. Together, those findings provide a path for further exploration of virulence mechanisms in parasitoid wasps, and offer insights into host-parasitoid coevolution.

Detecting and classifying cells in histopathology H\&E stained whole-slide images is a core task in computational pathology, as it provides valuable insight into the tumor microenvironment. In this work we investigate the impact of ground truth formats on the models performance. Additionally, cell-tissue interactions are considered by providing tissue segmentation predictions as input to the cell detection model. We find that a "soft", probability-map instance segmentation ground truth leads to best model performance. Combined with cell-tissue interaction and test-time augmentation our Soft Cell-Tissue-Model (SoftCTM) achieves 0.7172 mean F1-Score on the Overlapped Cell On Tissue (OCELOT) test set, achieving the third best overall score in the OCELOT 2023 Challenge. The source code for our approach is made publicly available at https://github.com/lely475/ocelot23algo.