Daily Papers

In this work, we introduce RadImageNet-VQA, a large-scale dataset designed to advance radiologic visual question answering (VQA) on CT and MRI exams. Existing medical VQA datasets are limited in scale, dominated by X-ray imaging or biomedical illustrations, and often prone to text-based shortcuts. RadImageNet-VQA is built from expert-curated annotations and provides 750K images paired with 7.5M question-answer samples. It covers three key tasks - abnormality detection, anatomy recognition, and pathology identification - spanning eight anatomical regions and 97 pathology categories, and supports open-ended, closed-ended, and multiple-choice questions. Extensive experiments show that state-of-the-art vision-language models still struggle with fine-grained pathology identification, particularly in open-ended settings and even after fine-tuning. Text-only analysis further reveals that model performance collapses to near-random without image inputs, confirming that RadImageNet-VQA is free from linguistic shortcuts. The full dataset and benchmark are publicly available at https://huggingface.co/datasets/raidium/RadImageNet-VQA.

Various screening and diagnostic methods have led to a large reduction of cervical cancer death rates in developed countries. However, cervical cancer is the leading cause of cancer related deaths in women in India and other low and middle income countries (LMICs) especially among the urban poor and slum dwellers. Several sophisticated techniques such as cytology tests, HPV tests etc. have been widely used for screening of cervical cancer. These tests are inherently time consuming. In this paper, we propose a convolutional autoencoder based framework, having an architecture similar to SegNet which is trained in an adversarial fashion for classifying images of the cervix acquired using a colposcope. We validate performance on the Intel-Mobile ODT cervical image classification dataset. The proposed method outperforms the standard technique of fine-tuning convolutional neural networks pre-trained on ImageNet database with an average accuracy of 73.75%.

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

Recently, intelligent analysis of lung nodules with the assistant of computer aided detection (CAD) techniques can improve the accuracy rate of lung cancer diagnosis. However, existing CAD systems and pulmonary datasets mainly focus on Computed Tomography (CT) images from one single period, while ignoring the cross spatio-temporal features associated with the progression of nodules contained in imaging data from various captured periods of lung cancer. If the evolution patterns of nodules across various periods in the patients' CT sequences can be explored, it will play a crucial role in guiding the precise screening identification of lung cancer. Therefore, a cross spatio-temporal lung nodule dataset with pathological information for nodule identification and diagnosis is constructed, which contains 328 CT sequences and 362 annotated nodules from 109 patients. This comprehensive database is intended to drive research in the field of CAD towards more practical and robust methods, and also contribute to the further exploration of precision medicine related field. To ensure patient confidentiality, we have removed sensitive information from the dataset.

Deep learning plays an important role in modern agriculture, especially in plant pathology using leaf images where convolutional neural networks (CNN) are attracting a lot of attention. While numerous reviews have explored the applications of deep learning within this research domain, there remains a notable absence of an empirical study to offer insightful comparisons due to the employment of varied datasets in the evaluation. Furthermore, a majority of these approaches tend to address the problem as a singular prediction task, overlooking the multifaceted nature of predicting various aspects of plant species and disease types. Lastly, there is an evident need for a more profound consideration of the semantic relationships that underlie plant species and disease types. In this paper, we start our study by surveying current deep learning approaches for plant identification and disease classification. We categorise the approaches into multi-model, multi-label, multi-output, and multi-task, in which different backbone CNNs can be employed. Furthermore, based on the survey of existing approaches in plant pathology and the study of available approaches in machine learning, we propose a new model named Generalised Stacking Multi-output CNN (GSMo-CNN). To investigate the effectiveness of different backbone CNNs and learning approaches, we conduct an intensive experiment on three benchmark datasets Plant Village, Plant Leaves, and PlantDoc. The experimental results demonstrate that InceptionV3 can be a good choice for a backbone CNN as its performance is better than AlexNet, VGG16, ResNet101, EfficientNet, MobileNet, and a custom CNN developed by us. Interestingly, empirical results support the hypothesis that using a single model can be comparable or better than using two models. Finally, we show that the proposed GSMo-CNN achieves state-of-the-art performance on three benchmark datasets.

Nuclear segmentation, classification and quantification within Haematoxylin & Eosin stained histology images enables the extraction of interpretable cell-based features that can be used in downstream explainable models in computational pathology (CPath). However, automatic recognition of different nuclei is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intra-class variability. To help drive forward research and innovation for automatic nuclei recognition in CPath, we organise the Colon Nuclei Identification and Counting (CoNIC) Challenge. The challenge encourages researchers to develop algorithms that perform segmentation, classification and counting of nuclei within the current largest known publicly available nuclei-level dataset in CPath, containing around half a million labelled nuclei. Therefore, the CoNIC challenge utilises over 10 times the number of nuclei as the previous largest challenge dataset for nuclei recognition. It is important for algorithms to be robust to input variation if we wish to deploy them in a clinical setting. Therefore, as part of this challenge we will also test the sensitivity of each submitted algorithm to certain input variations.

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.

Nuclear segmentation, classification and quantification within Haematoxylin & Eosin stained histology images enables the extraction of interpretable cell-based features that can be used in downstream explainable models in computational pathology (CPath). However, automatic recognition of different nuclei is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intraclass variability. In this work, we propose an approach that combine Separable-HoverNet and Instance-YOLOv5 to indentify colon nuclei small and unbalanced. Our approach can achieve mPQ+ 0.389 on the Segmentation and Classification-Preliminary Test Dataset and r2 0.599 on the Cellular Composition-Preliminary Test Dataset on ISBI 2022 CoNIC Challenge.

Pathology text mining is a challenging task given the reporting variability and constant new findings in cancer sub-type definitions. However, successful text mining of a large pathology database can play a critical role to advance 'big data' cancer research like similarity-based treatment selection, case identification, prognostication, surveillance, clinical trial screening, risk stratification, and many others. While there is a growing interest in developing language models for more specific clinical domains, no pathology-specific language space exist to support the rapid data-mining development in pathology space. In literature, a few approaches fine-tuned general transformer models on specialized corpora while maintaining the original tokenizer, but in fields requiring specialized terminology, these models often fail to perform adequately. We propose PathologyBERT - a pre-trained masked language model which was trained on 347,173 histopathology specimen reports and publicly released in the Huggingface repository. Our comprehensive experiments demonstrate that pre-training of transformer model on pathology corpora yields performance improvements on Natural Language Understanding (NLU) and Breast Cancer Diagnose Classification when compared to nonspecific language models.

Sensitivity to staining variation remains a major barrier to deploying computational pathology (CPath) models as hematoxylin and eosin (H&E) staining varies across laboratories, requiring systematic assessment of how this variability affects model prediction. In this work, we developed a three-step protocol for evaluating robustness to H&E staining variation in CPath models. Step 1: Select reference staining conditions, Step 2: Characterize test set staining properties, Step 3: Apply CPath model(s) under simulated reference staining conditions. Here, we first created a new reference staining library based on the PLISM dataset. As an exemplary use case, we applied the protocol to assess the robustness properties of 306 microsatellite instability (MSI) classification models on the unseen SurGen colorectal cancer dataset (n=738), including 300 attention-based multiple instance learning models trained on the TCGA-COAD/READ datasets across three feature extractors (UNI2-h, H-Optimus-1, Virchow2), alongside six public MSI classification models. Classification performance was measured as AUC, and robustness as the min-max AUC range across four simulated staining conditions (low/high H&E intensity, low/high H&E color similarity). Across models and staining conditions, classification performance ranged from AUC 0.769-0.911 (Δ = 0.142). Robustness ranged from 0.007-0.079 (Δ = 0.072), and showed a weak inverse correlation with classification performance (Pearson r=-0.22, 95% CI [-0.34, -0.11]). Thus, we show that the proposed evaluation protocol enables robustness-informed CPath model selection and provides insight into performance shifts across H&E staining conditions, supporting the identification of operational ranges for reliable model deployment. Code is available at https://github.com/CTPLab/staining-robustness-evaluation .

With the advent of the COVID-19 pandemic, ultrasound imaging has emerged as a promising technique for COVID-19 detection, due to its non-invasive nature, affordability, and portability. In response, researchers have focused on developing AI-based scoring systems to provide real-time diagnostic support. However, the limited size and lack of proper annotation in publicly available ultrasound datasets pose significant challenges for training a robust AI model. This paper proposes MeDiVLAD, a novel pipeline to address the above issue for multi-level lung-ultrasound (LUS) severity scoring. In particular, we leverage self-knowledge distillation to pretrain a vision transformer (ViT) without label and aggregate frame-level features via dual-level VLAD aggregation. We show that with minimal finetuning, MeDiVLAD outperforms conventional fully-supervised methods in both frame- and video-level scoring, while offering classification reasoning with exceptional quality. This superior performance enables key applications such as the automatic identification of critical lung pathology areas and provides a robust solution for broader medical video classification tasks.

Spine disorders affect 619 million people globally and are a leading cause of disability, yet AI-assisted diagnosis remains limited by the lack of level-aware, multimodal datasets. Clinical decision-making for spine disorders requires sophisticated reasoning across X-ray, CT, and MRI at specific vertebral levels. However, progress has been constrained by the absence of traceable, clinically-grounded instruction data and standardized, spine-specific benchmarks. To address this, we introduce SpineMed, an ecosystem co-designed with practicing spine surgeons. It features SpineMed-450k, the first large-scale dataset explicitly designed for vertebral-level reasoning across imaging modalities with over 450,000 instruction instances, and SpineBench, a clinically-grounded evaluation framework. SpineMed-450k is curated from diverse sources, including textbooks, guidelines, open datasets, and ~1,000 de-identified hospital cases, using a clinician-in-the-loop pipeline with a two-stage LLM generation method (draft and revision) to ensure high-quality, traceable data for question-answering, multi-turn consultations, and report generation. SpineBench evaluates models on clinically salient axes, including level identification, pathology assessment, and surgical planning. Our comprehensive evaluation of several recently advanced large vision-language models (LVLMs) on SpineBench reveals systematic weaknesses in fine-grained, level-specific reasoning. In contrast, our model fine-tuned on SpineMed-450k demonstrates consistent and significant improvements across all tasks. Clinician assessments confirm the diagnostic clarity and practical utility of our model's outputs.

Identifying effective interventions from the scientific literature is challenging due to the high volume of publications, specialized terminology, and inconsistent reporting formats, making manual curation laborious and prone to oversight. To address this challenge, this paper proposes a novel framework leveraging large language models (LLMs), which integrates a progressive ontology prompting (POP) algorithm with a dual-agent system, named LLM-Duo. On the one hand, the POP algorithm conducts a prioritized breadth-first search (BFS) across a predefined ontology, generating structured prompt templates and action sequences to guide the automatic annotation process. On the other hand, the LLM-Duo system features two specialized LLM agents, an explorer and an evaluator, working collaboratively and adversarially to continuously refine annotation quality. We showcase the real-world applicability of our framework through a case study focused on speech-language intervention discovery. Experimental results show that our approach surpasses advanced baselines, achieving more accurate and comprehensive annotations through a fully automated process. Our approach successfully identified 2,421 interventions from a corpus of 64,177 research articles in the speech-language pathology domain, culminating in the creation of a publicly accessible intervention knowledge base with great potential to benefit the speech-language pathology community.

Pathology is the study of microscopic inspection of tissue, and a pathology diagnosis is often the medical gold standard to diagnose disease. Pathology images provide a unique challenge for computer-vision-based analysis: a single pathology Whole Slide Image (WSI) is gigapixel-sized and often contains hundreds of thousands to millions of objects of interest across multiple resolutions. In this work, we propose PathoLogy Universal TransfOrmer (PLUTO): a light-weight pathology FM that is pre-trained on a diverse dataset of 195 million image tiles collected from multiple sites and extracts meaningful representations across multiple WSI scales that enable a large variety of downstream pathology tasks. In particular, we design task-specific adaptation heads that utilize PLUTO's output embeddings for tasks which span pathology scales ranging from subcellular to slide-scale, including instance segmentation, tile classification, and slide-level prediction. We compare PLUTO's performance to other state-of-the-art methods on a diverse set of external and internal benchmarks covering multiple biologically relevant tasks, tissue types, resolutions, stains, and scanners. We find that PLUTO matches or outperforms existing task-specific baselines and pathology-specific foundation models, some of which use orders-of-magnitude larger datasets and model sizes when compared to PLUTO. Our findings present a path towards a universal embedding to power pathology image analysis, and motivate further exploration around pathology foundation models in terms of data diversity, architectural improvements, sample efficiency, and practical deployability in real-world applications.

Pathological diagnosis remains the definitive standard for identifying tumors. The rise of multimodal large models has simplified the process of integrating image analysis with textual descriptions. Despite this advancement, the substantial costs associated with training and deploying these complex multimodal models, together with a scarcity of high-quality training datasets, create a significant divide between cutting-edge technology and its application in the clinical setting. We had meticulously compiled a dataset of approximately 45,000 cases, covering over 6 different tasks, including the classification of organ tissues, generating pathology report descriptions, and addressing pathology-related questions and answers. We have fine-tuned multimodal large models, specifically LLaVA, Qwen-VL, InternLM, with this dataset to enhance instruction-based performance. We conducted a qualitative assessment of the capabilities of the base model and the fine-tuned model in performing image captioning and classification tasks on the specific dataset. The evaluation results demonstrate that the fine-tuned model exhibits proficiency in addressing typical pathological questions. We hope that by making both our models and datasets publicly available, they can be valuable to the medical and research communities.

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.

Microscopic interpretation of histopathology images underlies many important diagnostic and treatment decisions. While advances in vision-language modeling raise new opportunities for analysis of such images, the gigapixel-scale size of whole slide images (WSIs) introduces unique challenges. Additionally, pathology reports simultaneously highlight key findings from small regions while also aggregating interpretation across multiple slides, often making it difficult to create robust image-text pairs. As such, pathology reports remain a largely untapped source of supervision in computational pathology, with most efforts relying on region-of-interest annotations or self-supervision at the patch-level. In this work, we develop a vision-language model based on the BLIP-2 framework using WSIs paired with curated text from pathology reports. This enables applications utilizing a shared image-text embedding space, such as text or image retrieval for finding cases of interest, as well as integration of the WSI encoder with a frozen large language model (LLM) for WSI-based generative text capabilities such as report generation or AI-in-the-loop interactions. We utilize a de-identified dataset of over 350,000 WSIs and diagnostic text pairs, spanning a wide range of diagnoses, procedure types, and tissue types. We present pathologist evaluation of text generation and text retrieval using WSI embeddings, as well as results for WSI classification and workflow prioritization (slide-level triaging). Model-generated text for WSIs was rated by pathologists as accurate, without clinically significant error or omission, for 78% of WSIs on average. This work demonstrates exciting potential capabilities for language-aligned WSI embeddings.

Pathology, the microscopic examination of diseased tissue, is critical for diagnosing various medical conditions, particularly cancers. Traditional methods are labor-intensive and prone to human error. Digital pathology, which converts glass slides into high-resolution digital images for analysis by computer algorithms, revolutionizes the field by enhancing diagnostic accuracy, consistency, and efficiency through automated image analysis and large-scale data processing. Foundational transformer pretraining is crucial for developing robust, generalizable models as it enables learning from vast amounts of unannotated data. This paper introduces the Hibou family of foundational vision transformers for pathology, leveraging the DINOv2 framework to pretrain two model variants, Hibou-B and Hibou-L, on a proprietary dataset of over 1 million whole slide images (WSIs) representing diverse tissue types and staining techniques. Our pretrained models demonstrate superior performance on both patch-level and slide-level benchmarks, surpassing existing state-of-the-art methods. Notably, Hibou-L achieves the highest average accuracy across multiple benchmark datasets. To support further research and application in the field, we have open-sourced the Hibou-B model, which can be accessed at https://github.com/HistAI/hibou

Pathology plays a critical role in diagnosing a wide range of diseases, yet existing approaches often rely heavily on task-specific models trained on extensive, well-labeled datasets. These methods face sustainability challenges due to the diversity of pathologies and the labor-intensive nature of data collection. To address these limitations, we highlight the need for universal multimodal embeddings that can support multiple downstream tasks. Previous approaches often involve fine-tuning CLIP-based models, which handle images and text separately, limiting their ability to capture complex multimodal relationships. Additionally, these models are evaluated across diverse datasets without a unified benchmark for assessing multimodal embeddings in pathology. To address these challenges, we propose MLLM4PUE, a novel framework that leverages Multimodal Large Language Models (MLLMs) to generate Pathology Universal Embeddings. The MLLM4PUE framework not only facilitates robust integration of images and text but also enhances understanding and fusion capabilities across various tasks. We further introduce the Pathology Multimodal Embedding Benchmark (PMEB), a comprehensive benchmark designed to assess the quality of pathology multimodal embeddings. PMEB comprises 15 original tasks drawn from 14 datasets, organized into three meta-tasks: retrieval, classification, and composed retrieval. Experimental results demonstrate the superiority of MLLM4PUE, illustrating MLLM-based models can effectively support a wide range of downstream tasks and unify the research direction for foundation models in pathology.

Metadata are general characteristics of the data in a well-curated and condensed format, and have been proven to be useful for decision making, knowledge discovery, and also heterogeneous data organization of biobank. Among all data types in the biobank, pathology is the key component of the biobank and also serves as the gold standard of diagnosis. To maximize the utility of biobank and allow the rapid progress of biomedical science, it is essential to organize the data with well-populated pathology metadata. However, manual annotation of such information is tedious and time-consuming. In the study, we develop a multimodal multitask learning framework to predict four major slide-level metadata of pathology images. The framework learns generalizable representations across tissue slides, pathology reports, and case-level structured data. We demonstrate improved performance across all four tasks with the proposed method compared to a single modal single task baseline on two test sets, one external test set from a distinct data source (TCGA) and one internal held-out test set (TTH). In the test sets, the performance improvements on the averaged area under receiver operating characteristic curve across the four tasks are 16.48% and 9.05% on TCGA and TTH, respectively. Such pathology metadata prediction system may be adopted to mitigate the effort of expert annotation and ultimately accelerate the data-driven research by better utilization of the pathology biobank.

Forensic pathology is critical in determining the cause and manner of death through post-mortem examinations, both macroscopic and microscopic. The field, however, grapples with issues such as outcome variability, laborious processes, and a scarcity of trained professionals. This paper presents SongCi, an innovative visual-language model (VLM) designed specifically for forensic pathology. SongCi utilizes advanced prototypical cross-modal self-supervised contrastive learning to enhance the accuracy, efficiency, and generalizability of forensic analyses. It was pre-trained and evaluated on a comprehensive multi-center dataset, which includes over 16 million high-resolution image patches, 2,228 vision-language pairs of post-mortem whole slide images (WSIs), and corresponding gross key findings, along with 471 distinct diagnostic outcomes. Our findings indicate that SongCi surpasses existing multi-modal AI models in many forensic pathology tasks, performs comparably to experienced forensic pathologists and significantly better than less experienced ones, and provides detailed multi-modal explainability, offering critical assistance in forensic investigations. To the best of our knowledge, SongCi is the first VLM specifically developed for forensic pathological analysis and the first large-vocabulary computational pathology (CPath) model that directly processes gigapixel WSIs in forensic science.

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

Vision-language models in pathology enable multimodal case retrieval and automated report generation. Many of the models developed so far, however, have been trained on pathology reports that include information which cannot be inferred from paired whole slide images (e.g., patient history), potentially leading to hallucinated sentences in generated reports. To this end, we investigate how the selection of information from pathology reports for vision-language modeling affects the quality of the multimodal representations and generated reports. More concretely, we compare a model trained on full reports against a model trained on preprocessed reports that only include sentences describing the cell and tissue appearances based on the H&E-stained slides. For the experiments, we built upon the BLIP-2 framework and used a cutaneous melanocytic lesion dataset of 42,433 H&E-stained whole slide images and 19,636 corresponding pathology reports. Model performance was assessed using image-to-text and text-to-image retrieval, as well as qualitative evaluation of the generated reports by an expert pathologist. Our results demonstrate that text preprocessing prevents hallucination in report generation. Despite the improvement in the quality of the generated reports, training the vision-language model on full reports showed better cross-modal retrieval performance.

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.

Foundation models trained with self-supervised learning (SSL) on large-scale histological images have significantly accelerated the development of computational pathology. These models can serve as backbones for region-of-interest (ROI) image analysis or patch-level feature extractors in whole-slide images (WSIs) based on multiple instance learning (MIL). Existing pathology foundation models (PFMs) are typically pre-trained on Hematoxylin-Eosin (H&E) stained pathology images. However, images with special stains, such as immunohistochemistry, are also frequently used in clinical practice. PFMs pre-trained mainly on H\&E-stained images may be limited in clinical applications involving special stains. To address this issue, we propose StainNet, a specialized foundation model for special stains based on the vision transformer (ViT) architecture. StainNet adopts a self-distillation SSL approach and is trained on over 1.4 million patch images cropping from 20,231 publicly available special staining WSIs in the HISTAI database. To evaluate StainNet, we conduct experiments on an in-house slide-level liver malignancy classification task and two public ROI-level datasets to demonstrate its strong ability. We also perform few-ratio learning and retrieval evaluations, and compare StainNet with recently larger PFMs to further highlight its strengths. We have released the StainNet model weights at: https://huggingface.co/JWonderLand/StainNet.

Recent advancements in digital pathology have led to the development of numerous foundational models that utilize self-supervised learning on patches extracted from gigapixel whole slide images (WSIs). While this approach leverages vast amounts of unlabeled data, we have discovered a significant issue: features extracted from these self-supervised models tend to cluster by individual WSIs, a phenomenon we term WSI-specific feature collapse. This problem can potentially limit the model's generalization ability and performance on various downstream tasks. To address this issue, we introduce Stain Normalized Pathology Foundational Model, a novel foundational model trained on patches that have undergone stain normalization. Stain normalization helps reduce color variability arising from different laboratories and scanners, enabling the model to learn more consistent features. Stain Normalized Pathology Foundational Model is trained using 285,153,903 patches extracted from a total of 34,795 WSIs, combining data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Our experiments demonstrate that Stain Normalized Pathology Foundational Model significantly mitigates the feature collapse problem, indicating that the model has learned more generalized features rather than overfitting to individual WSI characteristics. We compared Stain Normalized Pathology Foundational Model with state-of-the-art models across six downstream task datasets, and our results show that Stain Normalized Pathology Foundational Model achieves excellent performance relative to the number of WSIs used and the model's parameter count. This suggests that the application of stain normalization has substantially improved the model's efficiency and generalization capabilities.

Tissue phenotyping is a fundamental task in learning objective characterizations of histopathologic biomarkers within the tumor-immune microenvironment in cancer pathology. However, whole-slide imaging (WSI) is a complex computer vision in which: 1) WSIs have enormous image resolutions with precludes large-scale pixel-level efforts in data curation, and 2) diversity of morphological phenotypes results in inter- and intra-observer variability in tissue labeling. To address these limitations, current efforts have proposed using pretrained image encoders (transfer learning from ImageNet, self-supervised pretraining) in extracting morphological features from pathology, but have not been extensively validated. In this work, we conduct a search for good representations in pathology by training a variety of self-supervised models with validation on a variety of weakly-supervised and patch-level tasks. Our key finding is in discovering that Vision Transformers using DINO-based knowledge distillation are able to learn data-efficient and interpretable features in histology images wherein the different attention heads learn distinct morphological phenotypes. We make evaluation code and pretrained weights publicly-available at: https://github.com/Richarizardd/Self-Supervised-ViT-Path.

Tissue phenotyping is a fundamental computational pathology (CPath) task in learning objective characterizations of histopathologic biomarkers in anatomic pathology. However, whole-slide imaging (WSI) poses a complex computer vision problem in which the large-scale image resolutions of WSIs and the enormous diversity of morphological phenotypes preclude large-scale data annotation. Current efforts have proposed using pretrained image encoders with either transfer learning from natural image datasets or self-supervised pretraining on publicly-available histopathology datasets, but have not been extensively developed and evaluated across diverse tissue types at scale. We introduce UNI, a general-purpose self-supervised model for pathology, pretrained using over 100 million tissue patches from over 100,000 diagnostic haematoxylin and eosin-stained WSIs across 20 major tissue types, and evaluated on 33 representative CPath clinical tasks in CPath of varying diagnostic difficulties. In addition to outperforming previous state-of-the-art models, we demonstrate new modeling capabilities in CPath such as resolution-agnostic tissue classification, slide classification using few-shot class prototypes, and disease subtyping generalization in classifying up to 108 cancer types in the OncoTree code classification system. UNI advances unsupervised representation learning at scale in CPath in terms of both pretraining data and downstream evaluation, enabling data-efficient AI models that can generalize and transfer to a gamut of diagnostically-challenging tasks and clinical workflows in anatomic pathology.

Computational pathology can lead to saving human lives, but models are annotation hungry and pathology images are notoriously expensive to annotate. Self-supervised learning has shown to be an effective method for utilizing unlabeled data, and its application to pathology could greatly benefit its downstream tasks. Yet, there are no principled studies that compare SSL methods and discuss how to adapt them for pathology. To address this need, we execute the largest-scale study of SSL pre-training on pathology image data, to date. Our study is conducted using 4 representative SSL methods on diverse downstream tasks. We establish that large-scale domain-aligned pre-training in pathology consistently out-performs ImageNet pre-training in standard SSL settings such as linear and fine-tuning evaluations, as well as in low-label regimes. Moreover, we propose a set of domain-specific techniques that we experimentally show leads to a performance boost. Lastly, for the first time, we apply SSL to the challenging task of nuclei instance segmentation and show large and consistent performance improvements under diverse settings.

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.

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.

The field of computational pathology has been transformed with recent advances in foundation models that encode histopathology region-of-interests (ROIs) into versatile and transferable feature representations via self-supervised learning (SSL). However, translating these advancements to address complex clinical challenges at the patient and slide level remains constrained by limited clinical data in disease-specific cohorts, especially for rare clinical conditions. We propose TITAN, a multimodal whole slide foundation model pretrained using 335,645 WSIs via visual self-supervised learning and vision-language alignment with corresponding pathology reports and 423,122 synthetic captions generated from a multimodal generative AI copilot for pathology. Without any finetuning or requiring clinical labels, TITAN can extract general-purpose slide representations and generate pathology reports that generalize to resource-limited clinical scenarios such as rare disease retrieval and cancer prognosis. We evaluate TITAN on diverse clinical tasks and find that TITAN outperforms both ROI and slide foundation models across machine learning settings such as linear probing, few-shot and zero-shot classification, rare cancer retrieval and cross-modal retrieval, and pathology report generation.

In this paper we present a hybrid method for the automatic detection of dermatological pathologies in medical reports. We use a large language model combined with medical ontologies to predict, given a first appointment or follow-up medical report, the pathology a person may suffer from. The results show that teaching the model to learn the type, severity and location on the body of a dermatological pathology, as well as in which order it has to learn these three features, significantly increases its accuracy. The article presents the demonstration of state-of-the-art results for classification of medical texts with a precision of 0.84, micro and macro F1-score of 0.82 and 0.75, and makes both the method and the data set used available to the community.

Pathogen identification is pivotal in diagnosing, treating, and preventing diseases, crucial for controlling infections and safeguarding public health. Traditional alignment-based methods, though widely used, are computationally intense and reliant on extensive reference databases, often failing to detect novel pathogens due to their low sensitivity and specificity. Similarly, conventional machine learning techniques, while promising, require large annotated datasets and extensive feature engineering and are prone to overfitting. Addressing these challenges, we introduce PathoLM, a cutting-edge pathogen language model optimized for the identification of pathogenicity in bacterial and viral sequences. Leveraging the strengths of pre-trained DNA models such as the Nucleotide Transformer, PathoLM requires minimal data for fine-tuning, thereby enhancing pathogen detection capabilities. It effectively captures a broader genomic context, significantly improving the identification of novel and divergent pathogens. We developed a comprehensive data set comprising approximately 30 species of viruses and bacteria, including ESKAPEE pathogens, seven notably virulent bacterial strains resistant to antibiotics. Additionally, we curated a species classification dataset centered specifically on the ESKAPEE group. In comparative assessments, PathoLM dramatically outperforms existing models like DciPatho, demonstrating robust zero-shot and few-shot capabilities. Furthermore, we expanded PathoLM-Sp for ESKAPEE species classification, where it showed superior performance compared to other advanced deep learning methods, despite the complexities of the task.

Radiology reporting generative AI holds significant potential to alleviate clinical workloads and streamline medical care. However, achieving high clinical accuracy is challenging, as radiological images often feature subtle lesions and intricate structures. Existing systems often fall short, largely due to their reliance on fixed size, patch-level image features and insufficient incorporation of pathological information. This can result in the neglect of such subtle patterns and inconsistent descriptions of crucial pathologies. To address these challenges, we propose an innovative approach that leverages pathology-aware regional prompts to explicitly integrate anatomical and pathological information of various scales, significantly enhancing the precision and clinical relevance of generated reports. We develop an anatomical region detector that extracts features from distinct anatomical areas, coupled with a novel multi-label lesion detector that identifies global pathologies. Our approach emulates the diagnostic process of radiologists, producing clinically accurate reports with comprehensive diagnostic capabilities. Experimental results show that our model outperforms previous state-of-the-art methods on most natural language generation and clinical efficacy metrics, with formal expert evaluations affirming its potential to enhance radiology practice.

In computational pathology, understanding and generation have evolved along disparate paths: advanced understanding models already exhibit diagnostic-level competence, whereas generative models largely simulate pixels. Progress remains hindered by three coupled factors: the scarcity of large, high-quality image-text corpora; the lack of precise, fine-grained semantic control, which forces reliance on non-semantic cues; and terminological heterogeneity, where diverse phrasings for the same diagnostic concept impede reliable text conditioning. We introduce UniPath, a semantics-driven pathology image generation framework that leverages mature diagnostic understanding to enable controllable generation. UniPath implements Multi-Stream Control: a Raw-Text stream; a High-Level Semantics stream that uses learnable queries to a frozen pathology MLLM to distill paraphrase-robust Diagnostic Semantic Tokens and to expand prompts into diagnosis-aware attribute bundles; and a Prototype stream that affords component-level morphological control via a prototype bank. On the data front, we curate a 2.65M image-text corpus and a finely annotated, high-quality 68K subset to alleviate data scarcity. For a comprehensive assessment, we establish a four-tier evaluation hierarchy tailored to pathology. Extensive experiments demonstrate UniPath's SOTA performance, including a Patho-FID of 80.9 (51% better than the second-best) and fine-grained semantic control achieving 98.7% of the real-image. The meticulously curated datasets, complete source code, and pre-trained model weights developed in this study will be made openly accessible to the public.

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.

Computational pathology, which involves analyzing whole slide images for automated cancer diagnosis, relies on multiple instance learning, where performance depends heavily on the feature extractor and aggregator. Recent Pathology Foundation Models (PFMs), pretrained on large-scale histopathology data, have significantly enhanced both the extractor and aggregator, but they lack a systematic analysis framework. In this survey, we present a hierarchical taxonomy organizing PFMs through a top-down philosophy applicable to foundation model analysis in any domain: model scope, model pretraining, and model design. Additionally, we systematically categorize PFM evaluation tasks into slide-level, patch-level, multimodal, and biological tasks, providing comprehensive benchmarking criteria. Our analysis identifies critical challenges in both PFM development (pathology-specific methodology, end-to-end pretraining, data-model scalability) and utilization (effective adaptation, model maintenance), paving the way for future directions in this promising field. Resources referenced in this survey are available at https://github.com/BearCleverProud/AwesomeWSI.

Histopathology plays a central role in clinical medicine and biomedical research. While artificial intelligence shows promising results on many pathological tasks, generalization and dealing with rare diseases, where training data is scarce, remains a challenge. Distilling knowledge from unlabeled data into a foundation model before learning from, potentially limited, labeled data provides a viable path to address these challenges. In this work, we extend the state of the art of foundation models for digital pathology whole slide images by semi-automated data curation and incorporating pathologist domain knowledge. Specifically, we combine computational and pathologist domain knowledge (1) to curate a diverse dataset of 103k slides corresponding to 750 million image patches covering data from different fixation, staining, and scanning protocols as well as data from different indications and labs across the EU and US, (2) for grouping semantically similar slides and tissue patches, and (3) to augment the input images during training. We evaluate the resulting model on a set of public and internal benchmarks and show that although our foundation model is trained with an order of magnitude less slides, it performs on par or better than competing models. We expect that scaling our approach to more data and larger models will further increase its performance and capacity to deal with increasingly complex real world tasks in diagnostics and biomedical research.

Recent advancements in Digital Pathology (DP), particularly through artificial intelligence and Foundation Models, have underscored the importance of large-scale, diverse, and richly annotated datasets. Despite their critical role, publicly available Whole Slide Image (WSI) datasets often lack sufficient scale, tissue diversity, and comprehensive clinical metadata, limiting the robustness and generalizability of AI models. In response, we introduce the HISTAI dataset, a large, multimodal, open-access WSI collection comprising over 60,000 slides from various tissue types. Each case in the HISTAI dataset is accompanied by extensive clinical metadata, including diagnosis, demographic information, detailed pathological annotations, and standardized diagnostic coding. The dataset aims to fill gaps identified in existing resources, promoting innovation, reproducibility, and the development of clinically relevant computational pathology solutions. The dataset can be accessed at https://github.com/HistAI/HISTAI.

Recent breakthroughs in self-supervised learning have enabled the use of large unlabeled datasets to train visual foundation models that can generalize to a variety of downstream tasks. While this training paradigm is well suited for the medical domain where annotations are scarce, large-scale pre-training in the medical domain, and in particular pathology, has not been extensively studied. Previous work in self-supervised learning in pathology has leveraged smaller datasets for both pre-training and evaluating downstream performance. The aim of this project is to train the largest academic foundation model and benchmark the most prominent self-supervised learning algorithms by pre-training and evaluating downstream performance on large clinical pathology datasets. We collected the largest pathology dataset to date, consisting of over 3 billion images from over 423 thousand microscopy slides. We compared pre-training of visual transformer models using the masked autoencoder (MAE) and DINO algorithms. We evaluated performance on six clinically relevant tasks from three anatomic sites and two institutions: breast cancer detection, inflammatory bowel disease detection, breast cancer estrogen receptor prediction, lung adenocarcinoma EGFR mutation prediction, and lung cancer immunotherapy response prediction. Our results demonstrate that pre-training on pathology data is beneficial for downstream performance compared to pre-training on natural images. Additionally, the DINO algorithm achieved better generalization performance across all tasks tested. The presented results signify a phase change in computational pathology research, paving the way into a new era of more performant models based on large-scale, parallel pre-training at the billion-image scale.

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

Computational pathology (CPath) digitizes pathology slides into whole slide images (WSIs), enabling analysis for critical healthcare tasks such as cancer diagnosis and prognosis. However, WSIs possess extremely long sequence lengths (up to 200K), significant length variations (from 200 to 200K), and limited supervision. These extreme variations in sequence length lead to high data heterogeneity and redundancy. Conventional methods often compromise on training efficiency and optimization to preserve such heterogeneity under limited supervision. To comprehensively address these challenges, we propose a pack-based MIL framework. It packs multiple sampled, variable-length feature sequences into fixed-length ones, enabling batched training while preserving data heterogeneity. Moreover, we introduce a residual branch that composes discarded features from multiple slides into a hyperslide which is trained with tailored labels. It offers multi-slide supervision while mitigating feature loss from sampling. Meanwhile, an attention-driven downsampler is introduced to compress features in both branches to reduce redundancy. By alleviating these challenges, our approach achieves an accuracy improvement of up to 8% while using only 12% of the training time in the PANDA(UNI). Extensive experiments demonstrate that focusing data challenges in CPath holds significant potential in the era of foundation models. The code is https://github.com/FangHeng/PackMIL

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.

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.

Computational pathology foundation models (CPathFMs) have emerged as a powerful approach for analyzing histopathological data, leveraging self-supervised learning to extract robust feature representations from unlabeled whole-slide images. These models, categorized into uni-modal and multi-modal frameworks, have demonstrated promise in automating complex pathology tasks such as segmentation, classification, and biomarker discovery. However, the development of CPathFMs presents significant challenges, such as limited data accessibility, high variability across datasets, the necessity for domain-specific adaptation, and the lack of standardized evaluation benchmarks. This survey provides a comprehensive review of CPathFMs in computational pathology, focusing on datasets, adaptation strategies, and evaluation tasks. We analyze key techniques, such as contrastive learning and multi-modal integration, and highlight existing gaps in current research. Finally, we explore future directions from four perspectives for advancing CPathFMs. This survey serves as a valuable resource for researchers, clinicians, and AI practitioners, guiding the advancement of CPathFMs toward robust and clinically applicable AI-driven pathology solutions.

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.

Histology review is often used as the `gold standard' for disease diagnosis. Computer aided diagnosis tools can potentially help improve current pathology workflows by reducing examination time and interobserver variability. Previous work in cancer grading has focused mainly on classifying pre-defined regions of interest (ROIs), or relied on large amounts of fine-grained labels. In this paper, we propose a two-stage attention-based multiple instance learning model for slide-level cancer grading and weakly-supervised ROI detection and demonstrate its use in prostate cancer. Compared with existing Gleason classification models, our model goes a step further by utilizing visualized saliency maps to select informative tiles for fine-grained grade classification. The model was primarily developed on a large-scale whole slide dataset consisting of 3,521 prostate biopsy slides with only slide-level labels from 718 patients. The model achieved state-of-the-art performance for prostate cancer grading with an accuracy of 85.11\% for classifying benign, low-grade (Gleason grade 3+3 or 3+4), and high-grade (Gleason grade 4+3 or higher) slides on an independent test set.

Multiple Instance learning (MIL) models have been extensively used in pathology to predict biomarkers and risk-stratify patients from gigapixel-sized images. Machine learning problems in medical imaging often deal with rare diseases, making it important for these models to work in a label-imbalanced setting. In pathology images, there is another level of imbalance, where given a positively labeled Whole Slide Image (WSI), only a fraction of pixels within it contribute to the positive label. This compounds the severity of imbalance and makes imbalanced classification in pathology challenging. Furthermore, these imbalances can occur in out-of-distribution (OOD) datasets when the models are deployed in the real-world. We leverage the idea that decoupling feature and classifier learning can lead to improved decision boundaries for label imbalanced datasets. To this end, we investigate the integration of supervised contrastive learning with multiple instance learning (SC-MIL). Specifically, we propose a joint-training MIL framework in the presence of label imbalance that progressively transitions from learning bag-level representations to optimal classifier learning. We perform experiments with different imbalance settings for two well-studied problems in cancer pathology: subtyping of non-small cell lung cancer and subtyping of renal cell carcinoma. SC-MIL provides large and consistent improvements over other techniques on both in-distribution (ID) and OOD held-out sets across multiple imbalanced settings.

Immunohistochemistry (IHC) provides information on protein expression in tissue sections and is commonly used to support pathology diagnosis and disease triage. While AI models for H\&E-stained slides show promise, their applicability to IHC is limited due to domain-specific variations. Here we introduce HPA10M, a dataset that contains 10,495,672 IHC images from the Human Protein Atlas with comprehensive metadata included, and encompasses 45 normal tissue types and 20 major cancer types. Based on HPA10M, we trained iSight, a multi-task learning framework for automated IHC staining assessment. iSight combines visual features from whole-slide images with tissue metadata through a token-level attention mechanism, simultaneously predicting staining intensity, location, quantity, tissue type, and malignancy status. On held-out data, iSight achieved 85.5\% accuracy for location, 76.6\% for intensity, and 75.7\% for quantity, outperforming fine-tuned foundation models (PLIP, CONCH) by 2.5--10.2\%. In addition, iSight demonstrates well-calibrated predictions with expected calibration errors of 0.0150-0.0408. Furthermore, in a user study with eight pathologists evaluating 200 images from two datasets, iSight outperformed initial pathologist assessments on the held-out HPA dataset (79\% vs 68\% for location, 70\% vs 57\% for intensity, 68\% vs 52\% for quantity). Inter-pathologist agreement also improved after AI assistance in both held-out HPA (Cohen's κ increased from 0.63 to 0.70) and Stanford TMAD datasets (from 0.74 to 0.76), suggesting expert--AI co-assessment can improve IHC interpretation. This work establishes a foundation for AI systems that can improve IHC diagnostic accuracy and highlights the potential for integrating iSight into clinical workflows to enhance the consistency and reliability of IHC assessment.

Representation learning of pathology whole-slide images (WSIs) has been has primarily relied on weak supervision with Multiple Instance Learning (MIL). However, the slide representations resulting from this approach are highly tailored to specific clinical tasks, which limits their expressivity and generalization, particularly in scenarios with limited data. Instead, we hypothesize that morphological redundancy in tissue can be leveraged to build a task-agnostic slide representation in an unsupervised fashion. To this end, we introduce PANTHER, a prototype-based approach rooted in the Gaussian mixture model that summarizes the set of WSI patches into a much smaller set of morphological prototypes. Specifically, each patch is assumed to have been generated from a mixture distribution, where each mixture component represents a morphological exemplar. Utilizing the estimated mixture parameters, we then construct a compact slide representation that can be readily used for a wide range of downstream tasks. By performing an extensive evaluation of PANTHER on subtyping and survival tasks using 13 datasets, we show that 1) PANTHER outperforms or is on par with supervised MIL baselines and 2) the analysis of morphological prototypes brings new qualitative and quantitative insights into model interpretability.

Is it possible to develop an "AI Pathologist" to pass the board-certified examination of the American Board of Pathology? To achieve this goal, the first step is to create a visual question answering (VQA) dataset where the AI agent is presented with a pathology image together with a question and is asked to give the correct answer. Our work makes the first attempt to build such a dataset. Different from creating general-domain VQA datasets where the images are widely accessible and there are many crowdsourcing workers available and capable of generating question-answer pairs, developing a medical VQA dataset is much more challenging. First, due to privacy concerns, pathology images are usually not publicly available. Second, only well-trained pathologists can understand pathology images, but they barely have time to help create datasets for AI research. To address these challenges, we resort to pathology textbooks and online digital libraries. We develop a semi-automated pipeline to extract pathology images and captions from textbooks and generate question-answer pairs from captions using natural language processing. We collect 32,799 open-ended questions from 4,998 pathology images where each question is manually checked to ensure correctness. To our best knowledge, this is the first dataset for pathology VQA. Our dataset will be released publicly to promote research in medical VQA.

Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis suffers from limited reproducibility and diagnostic variability. To overcome these limitations, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on over 353 million multi-scale images from 210,043 H&E-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, protein expression status prediction, gene mutation prediction, and prognosis evaluation. We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.70% sensitivity across nine independent medical institutions. This work not only advances AI-driven precision pathology for GI diseases but also bridge critical gaps in histopathological practice.

Pancreatic cancer is one of the leading causes of cancer-related death. Accurate detection, segmentation, and differential diagnosis of the full taxonomy of pancreatic lesions, i.e., normal, seven major types of lesions, and other lesions, is critical to aid the clinical decision-making of patient management and treatment. However, existing works focus on segmentation and classification for very specific lesion types (PDAC) or groups. Moreover, none of the previous work considers using lesion prevalence-related non-imaging patient information to assist the differential diagnosis. To this end, we develop a meta-information-aware dual-path transformer and exploit the feasibility of classification and segmentation of the full taxonomy of pancreatic lesions. Specifically, the proposed method consists of a CNN-based segmentation path (S-path) and a transformer-based classification path (C-path). The S-path focuses on initial feature extraction by semantic segmentation using a UNet-based network. The C-path utilizes both the extracted features and meta-information for patient-level classification based on stacks of dual-path transformer blocks that enhance the modeling of global contextual information. A large-scale multi-phase CT dataset of 3,096 patients with pathology-confirmed pancreatic lesion class labels, voxel-wise manual annotations of lesions from radiologists, and patient meta-information, was collected for training and evaluations. Our results show that our method can enable accurate classification and segmentation of the full taxonomy of pancreatic lesions, approaching the accuracy of the radiologist's report and significantly outperforming previous baselines. Results also show that adding the common meta-information, i.e., gender and age, can boost the model's performance, thus demonstrating the importance of meta-information for aiding pancreatic disease diagnosis.

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.

The expanding ecosystem of pathology foundation models has produced powerful but fragmented tile-level representations, limiting their use in clinical tasks that require unified slide-level reasoning and interpretable linkage to clinically meaningful information. We present ASTRA, a pan-cancer framework that integrates heterogeneous foundation-model representations into a shared slide-level representation space and semantically grounds that space using structured pathology annotation fields, including classification category, cancer type, and anatomic site. ASTRA combines sparse mixture-of-experts contextualization, masked multi-model reconstruction, and contrastive alignment to structured pathology prompts to learn slide representations that support 4-category classification, 3-class solid tumor typing, 16-class cancer typing, and text-guided tumor localization without pixel-level supervision. Developed on a CHTN cohort of 10,359 whole-slide images (WSIs) spanning 16 tumor types, ASTRA consistently improves pan-cancer classification across four pathology foundation-model backbones, achieving up to 97.8% macro-AUC for 4-category classification, 99.7% for 3-class solid tumor typing, and 99.2% for 16-class cancer typing. For tumor localization, ASTRA achieves a mean Dice of 0.897 on an annotated in-domain CHTN subset (n = 380) spanning 16 cancer types and 0.738 on an external TCGA cohort (n = 1,686) spanning four cancer types. These results demonstrate that minimal structured pathology annotation fields derived from slide-level metadata can provide effective semantic supervision for unified slide representation learning, enabling both pan-cancer prediction and weakly supervised tumor localization within a single framework.

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.

The previous advancements in pathology image understanding primarily involved developing models tailored to specific tasks. Recent studies has demonstrated that the large vision-language model can enhance the performance of various downstream tasks in medical image understanding. In this study, we developed a domain-specific large language-vision assistant (PA-LLaVA) for pathology image understanding. Specifically, (1) we first construct a human pathology image-text dataset by cleaning the public medical image-text data for domain-specific alignment; (2) Using the proposed image-text data, we first train a pathology language-image pretraining (PLIP) model as the specialized visual encoder for pathology image, and then we developed scale-invariant connector to avoid the information loss caused by image scaling; (3) We adopt two-stage learning to train PA-LLaVA, first stage for domain alignment, and second stage for end to end visual question \& answering (VQA) task. In experiments, we evaluate our PA-LLaVA on both supervised and zero-shot VQA datasets, our model achieved the best overall performance among multimodal models of similar scale. The ablation experiments also confirmed the effectiveness of our design. We posit that our PA-LLaVA model and the datasets presented in this work can promote research in field of computational pathology. All codes are available at: https://github.com/ddw2AIGROUP2CQUPT/PA-LLaVA}{https://github.com/ddw2AIGROUP2CQUPT/PA-LLaVA

Accurate classification of pediatric central nervous system tumors remains challenging due to histological complexity and limited training data. While pathology foundation models have advanced whole-slide image (WSI) analysis, they often fail to leverage the rich, complementary information found in clinical text and tissue microarchitecture. To this end, we propose PathMoE, an interpretable multimodal framework that integrates H\&E slides, pathology reports, and nuclei-level cell graphs via an interaction-aware mixture-of-experts architecture built on state-of-the-art foundation models for each modality. By training specialized experts to capture modality uniqueness, redundancy, and synergy, PathMoE employs an input-dependent gating mechanism that dynamically weights these interactions, providing sample-level interpretability. We evaluate our framework on two dataset-specific classification tasks on an internal pediatric brain tumor dataset (PBT) and external TCGA datasets. PathMoE improves macro-F1 from 0.762 to 0.799 (+0.037) on PBT when integrating WSI, text, and graph modalities; on TCGA, augmenting WSI with graph knowledge improves macro-F1 from 0.668 to 0.709 (+0.041). These results demonstrate significant performance gains over state-of-the-art image-only baselines while revealing the specific modality interactions driving individual predictions. This interpretability is particularly critical for rare tumor subtypes, where transparent model reasoning is essential for clinical trust and diagnostic validation.

Content generation modeling has emerged as a promising direction in computational pathology, offering capabilities such as data-efficient learning, synthetic data augmentation, and task-oriented generation across diverse diagnostic tasks. This review provides a comprehensive synthesis of recent progress in the field, organized into four key domains: image generation, text generation, molecular profile-morphology generation, and other specialized generation applications. By analyzing over 150 representative studies, we trace the evolution of content generation architectures -- from early generative adversarial networks to recent advances in diffusion models and generative vision-language models. We further examine the datasets and evaluation protocols commonly used in this domain and highlight ongoing limitations, including challenges in generating high-fidelity whole slide images, clinical interpretability, and concerns related to the ethical and legal implications of synthetic data. The review concludes with a discussion of open challenges and prospective research directions, with an emphasis on developing integrated and clinically deployable generation systems. This work aims to provide a foundational reference for researchers and practitioners developing content generation models in computational pathology.

The field of computational pathology has recently seen rapid advances driven by the development of modern vision foundation models (FMs), typically trained on vast collections of pathology images. Recent studies demonstrate that increasing the training data set and model size and integrating domain-specific image processing techniques can significantly enhance the model's performance on downstream tasks. Building on these insights, our work incorporates several recent modifications to the standard DINOv2 framework from the literature to optimize the training of pathology FMs. We also apply a post-training procedure for fine-tuning models on higher-resolution images to further enrich the information encoded in the embeddings. We present three novel pathology FMs trained on up to two orders of magnitude fewer WSIs than those used to train other state-of-the-art FMs while demonstrating a comparable or superior performance on downstream tasks. Even the model trained on TCGA alone (12k WSIs) outperforms most existing FMs and, on average, matches Virchow2, the second-best FM published to date. This suggests that there still remains a significant potential for further improving the models and algorithms used to train pathology FMs to take full advantage of the vast data collections.

Virtual immunohistochemistry (IHC) staining from hematoxylin and eosin (H&E) images can accelerate diagnostics by providing preliminary molecular insight directly from routine sections, reducing the need for repeat sectioning when tissue is limited. Existing methods improve realism through contrastive objectives, prototype matching, or domain alignment, yet the generator itself receives no direct guidance from pathology foundation models. We present UNIStainNet, a SPADE-UNet conditioned on dense spatial tokens from a frozen pathology foundation model (UNI), providing tissue-level semantic guidance for stain translation. A misalignment-aware loss suite preserves stain quantification accuracy, and learned stain embeddings enable a single model to serve multiple IHC markers simultaneously. On MIST, UNIStainNet achieves state-of-the-art distributional metrics on all four stains (HER2, Ki67, ER, PR) from a single unified model, where prior methods typically train separate per-stain models. On BCI, it also achieves the best distributional metrics. A tissue-type stratified failure analysis reveals that remaining errors are systematic, concentrating in non-tumor tissue. Code is available at https://github.com/facevoid/UNIStainNet.

The recent surge of foundation models in computer vision and natural language processing opens up perspectives in utilizing multi-modal clinical data to train large models with strong generalizability. Yet pathological image datasets often lack biomedical text annotation and enrichment. Guiding data-efficient image diagnosis from the use of biomedical text knowledge becomes a substantial interest. In this paper, we propose to Connect Image and Text Embeddings (CITE) to enhance pathological image classification. CITE injects text insights gained from language models pre-trained with a broad range of biomedical texts, leading to adapt foundation models towards pathological image understanding. Through extensive experiments on the PatchGastric stomach tumor pathological image dataset, we demonstrate that CITE achieves leading performance compared with various baselines especially when training data is scarce. CITE offers insights into leveraging in-domain text knowledge to reinforce data-efficient pathological image classification. Code is available at https://github.com/Yunkun-Zhang/CITE.

Explaining deep learning models is essential for clinical integration of medical image analysis systems. A good explanation highlights if a model depends on spurious features that undermines generalization and harms a subset of patients or, conversely, may present novel biological insights. Although techniques like GradCAM can identify influential features, they are measurement tools that do not themselves form an explanation. We propose a human-machine-VLM interaction system tailored to explaining classifiers in computational pathology, including multi-instance learning for whole-slide images. Our proof of concept comprises (1) an AI-integrated slide viewer to run sliding-window experiments to test claims of an explanation, and (2) quantification of an explanation's predictiveness using general-purpose vision-language models. The results demonstrate that this allows us to qualitatively test claims of explanations and can quantifiably distinguish competing explanations. This offers a practical path from explainable AI to explained AI in digital pathology and beyond. Code and prompts are available at https://github.com/nki-ai/x2x.

Foundation models in computational pathology promise to unlock the development of new clinical decision support systems and models for precision medicine. However, there is a mismatch between most clinical analysis, which is defined at the level of one or more whole slide images, and foundation models to date, which process the thousands of image tiles contained in a whole slide image separately. The requirement to train a network to aggregate information across a large number of tiles in multiple whole slide images limits these models' impact. In this work, we present a slide-level foundation model for H&E-stained histopathology, PRISM, that builds on Virchow tile embeddings and leverages clinical report text for pre-training. Using the tile embeddings, PRISM produces slide-level embeddings with the ability to generate clinical reports, resulting in several modes of use. Using text prompts, PRISM achieves zero-shot cancer detection and sub-typing performance approaching and surpassing that of a supervised aggregator model. Using the slide embeddings with linear classifiers, PRISM surpasses supervised aggregator models. Furthermore, we demonstrate that fine-tuning of the PRISM slide encoder yields label-efficient training for biomarker prediction, a task that typically suffers from low availability of training data; an aggregator initialized with PRISM and trained on as little as 10% of the training data can outperform a supervised baseline that uses all of the data.

The digitization of histology slides has revolutionized pathology, providing massive datasets for cancer diagnosis and research. Contrastive self-supervised and vision-language models have been shown to effectively mine large pathology datasets to learn discriminative representations. On the other hand, generative models, capable of synthesizing realistic and diverse images, present a compelling solution to address unique problems in pathology that involve synthesizing images; overcoming annotated data scarcity, enabling privacy-preserving data sharing, and performing inherently generative tasks, such as virtual staining. We introduce PixCell, the first diffusion-based generative foundation model for histopathology. We train PixCell on PanCan-30M, a vast, diverse dataset derived from 69,184 H\&E-stained whole slide images covering various cancer types. We employ a progressive training strategy and a self-supervision-based conditioning that allows us to scale up training without any annotated data. PixCell generates diverse and high-quality images across multiple cancer types, which we find can be used in place of real data to train a self-supervised discriminative model. Synthetic images shared between institutions are subject to fewer regulatory barriers than would be the case with real clinical images. Furthermore, we showcase the ability to precisely control image generation using a small set of annotated images, which can be used for both data augmentation and educational purposes. Testing on a cell segmentation task, a mask-guided PixCell enables targeted data augmentation, improving downstream performance. Finally, we demonstrate PixCell's ability to use H\&E structural staining to infer results from molecular marker studies; we use this capability to infer IHC staining from H\&E images. Our trained models are publicly released to accelerate research in computational pathology.

Pathology foundation models substantially advanced the possibilities in computational pathology -- yet tradeoffs in terms of performance, robustness, and computational requirements remained, which limited their clinical deployment. In this report, we present Atlas 2, Atlas 2-B, and Atlas 2-S, three pathology vision foundation models which bridge these shortcomings by showing state-of-the-art performance in prediction performance, robustness, and resource efficiency in a comprehensive evaluation across eighty public benchmarks. Our models were trained on the largest pathology foundation model dataset to date comprising 5.5 million histopathology whole slide images, collected from three medical institutions Charité - Universtätsmedizin Berlin, LMU Munich, and Mayo Clinic.

Considering the increased workload in pathology laboratories today, automated tools such as artificial intelligence models can help pathologists with their tasks and ease the workload. In this paper, we are proposing a segmentation model (DRU-Net) that can provide a delineation of human non-small cell lung carcinomas and an augmentation method that can improve classification results. The proposed model is a fused combination of truncated pre-trained DenseNet201 and ResNet101V2 as a patch-wise classifier followed by a lightweight U-Net as a refinement model. We have used two datasets (Norwegian Lung Cancer Biobank and Haukeland University Hospital lung cancer cohort) to create our proposed model. The DRU-Net model achieves an average of 0.91 Dice similarity coefficient. The proposed spatial augmentation method (multi-lens distortion) improved the network performance by 3%. Our findings show that choosing image patches that specifically include regions of interest leads to better results for the patch-wise classifier compared to other sampling methods. The qualitative analysis showed that the DRU-Net model is generally successful in detecting the tumor. On the test set, some of the cases showed areas of false positive and false negative segmentation in the periphery, particularly in tumors with inflammatory and reactive changes.

Foundation models have recently achieved impressive success in computational pathology, demonstrating strong generalization across diverse histopathology tasks. However, existing models overlook the heterogeneous and non-uniform organization of pathological regions of interest (ROIs) because they rely on natural image backbones not tailored for tissue morphology. Consequently, they often fail to capture the coherent tissue architecture beyond isolated patches, limiting interpretability and clinical relevance. To address these challenges, we present Cross-modal Adaptive Region Encoder (CARE), a foundation model for pathology that automatically partitions WSIs into several morphologically relevant regions. Specifically, CARE employs a two-stage pretraining strategy: (1) a self-supervised unimodal pretraining stage that learns morphological representations from 34,277 whole-slide images (WSIs) without segmentation annotations, and (2) a cross-modal alignment stage that leverages RNA and protein profiles to refine the construction and representation of adaptive regions. This molecular guidance enables CARE to identify biologically relevant patterns and generate irregular yet coherent tissue regions, selecting the most representative area as ROI. CARE supports a broad range of pathology-related tasks, using either the ROI feature or the slide-level feature obtained by aggregating adaptive regions. Based on only one-tenth of the pretraining data typically used by mainstream foundation models, CARE achieves superior average performance across 33 downstream benchmarks, including morphological classification, molecular prediction, and survival analysis, and outperforms other foundation model baselines overall.

The use of artificial intelligence to enable precision medicine and decision support systems through the analysis of pathology images has the potential to revolutionize the diagnosis and treatment of cancer. Such applications will depend on models' abilities to capture the diverse patterns observed in pathology images. To address this challenge, we present Virchow, a foundation model for computational pathology. Using self-supervised learning empowered by the DINOv2 algorithm, Virchow is a vision transformer model with 632 million parameters trained on 1.5 million hematoxylin and eosin stained whole slide images from diverse tissue and specimen types, which is orders of magnitude more data than previous works. The Virchow model enables the development of a pan-cancer detection system with 0.949 overall specimen-level AUC across 17 different cancer types, while also achieving 0.937 AUC on 7 rare cancer types. The Virchow model sets the state-of-the-art on the internal and external image tile level benchmarks and slide level biomarker prediction tasks. The gains in performance highlight the importance of training on massive pathology image datasets, suggesting scaling up the data and network architecture can improve the accuracy for many high-impact computational pathology applications where limited amounts of training data are available.

While machine learning is currently transforming the field of histopathology, the domain lacks a comprehensive evaluation of state-of-the-art models based on essential but complementary quality requirements beyond a mere classification accuracy. In order to fill this gap, we developed a new methodology to extensively evaluate a wide range of classification models, including recent vision transformers, and convolutional neural networks such as: ConvNeXt, ResNet (BiT), Inception, ViT and Swin transformer, with and without supervised or self-supervised pretraining. We thoroughly tested the models on five widely used histopathology datasets containing whole slide images of breast, gastric, and colorectal cancer and developed a novel approach using an image-to-image translation model to assess the robustness of a cancer classification model against stain variations. Further, we extended existing interpretability methods to previously unstudied models and systematically reveal insights of the models' classifications strategies that can be transferred to future model architectures.

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.

Mitotic figures are classified into typical and atypical variants, with atypical counts correlating strongly with tumor aggressiveness. Accurate differentiation is therefore essential for patient prognostication and resource allocation, yet remains challenging even for expert pathologists. Here, we leveraged Pathology Foundation Models (PFMs) pre-trained on large histopathology datasets and applied parameter-efficient fine-tuning via low-rank adaptation. In addition, we incorporated ConvNeXt V2, a state-of-the-art convolutional neural network architecture, to complement PFMs. During training, we employed a fisheye transform to emphasize mitoses and Fourier Domain Adaptation using ImageNet target images. Finally, we ensembled multiple PFMs to integrate complementary morphological insights, achieving competitive balanced accuracy on the Preliminary Evaluation Phase dataset.

Microscopic assessment of histopathology images is vital for accurate cancer diagnosis and treatment. Whole Slide Image (WSI) classification and captioning have become crucial tasks in computer-aided pathology. However, microscopic WSI face challenges such as redundant patches and unknown patch positions due to subjective pathologist captures. Moreover, generating automatic pathology captions remains a significant challenge. To address these issues, we introduce a novel GNN-ViTCap framework for classification and caption generation from histopathological microscopic images. First, a visual feature extractor generates patch embeddings. Redundant patches are then removed by dynamically clustering these embeddings using deep embedded clustering and selecting representative patches via a scalar dot attention mechanism. We build a graph by connecting each node to its nearest neighbors in the similarity matrix and apply a graph neural network to capture both local and global context. The aggregated image embeddings are projected into the language model's input space through a linear layer and combined with caption tokens to fine-tune a large language model. We validate our method on the BreakHis and PatchGastric datasets. GNN-ViTCap achieves an F1 score of 0.934 and an AUC of 0.963 for classification, along with a BLEU-4 score of 0.811 and a METEOR score of 0.569 for captioning. Experimental results demonstrate that GNN-ViTCap outperforms state of the art approaches, offering a reliable and efficient solution for microscopy based patient diagnosis.

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.

Computational pathology has made significant progress in recent years, fueling advances in both fundamental disease understanding and clinically ready tools. This evolution is driven by the availability of large amounts of digitized slides and specialized deep learning methods and models. Multiple self-supervised foundation feature extractors have been developed, enabling downstream predictive applications from cell segmentation to tumor sub-typing and survival analysis. In contrast, generative foundation models designed specifically for histopathology remain scarce. Such models could address tasks that are beyond the capabilities of feature extractors, such as virtual staining. In this paper, we introduce CytoSyn, a state-of-the-art foundation latent diffusion model that enables the guided generation of highly realistic and diverse histopathology H&E-stained images, as shown in an extensive benchmark. We explored methodological improvements, training set scaling, sampling strategies and slide-level overfitting, culminating in the improved CytoSyn-v2, and compared our work to PixCell, a state-of-the-art model, in an in-depth manner. This comparison highlighted the strong sensitivity of both diffusion models and performance metrics to preprocessing-specific details such as JPEG compression. Our model has been trained on a dataset obtained from more than 10,000 TCGA diagnostic whole-slide images of 32 different cancer types. Despite being trained only on oncology slides, it maintains state-of-the-art performance generating inflammatory bowel disease images. To support the research community, we publicly release CytoSyn's weights, its training and validation datasets, and a sample of synthetic images in this repository: https://huggingface.co/Owkin-Bioptimus/CytoSyn.

Computational pathology relies on effective representation learning to support cancer research and precision medicine. Although self-supervised learning has driven major progress at the patch and whole-slide image levels, representation learning at the single-cell level remains comparatively underexplored, despite its importance for characterizing cell types and cellular phenotypes. We introduce LEMON (Learning Embeddings from Morphology Of Nuclei), a self-supervised foundation model for scalable single-cell image representation learning. Trained on millions of cell images from diverse tissues and cancer types, LEMON learns robust and versatile morphological representations that support large-scale single-cell analyses in pathology. We evaluate LEMON on five benchmark datasets across a range of prediction tasks and show that it provides strong performance, highlighting its potential as a new paradigm for cell-level computational pathology. Model weights are available at https://huggingface.co/aliceblondel/LEMON.

Cell-level dense prediction is central to computational pathology, but remains challenging due to fine-grained histological structures, strong domain shifts, and costly dense annotations. Existing ViT-based pathology foundation models rely on patch tokenization, which can disrupt spatial continuity and weaken local morphological details needed for cell-level prediction. To address this, we propose Masked-Diffusion Convolutional Foundation Models, termed ConvNeXt Masked-Diffusion (CMD), a self-supervised convolutional generative pretraining framework for dense pathology representation learning. CMD uses a fully convolutional ConvNeXt-UNet backbone, performs masked-diffusion pretraining in pixel space, and incorporates frozen pathology foundation model features through adaptive normalization. Experimental results demonstrate that CMD consistently outperforms existing ViT-based pathology foundation models and even surpasses state-of-the-art end-to-end segmentation methods while fine-tuning only a small number of task-specific parameters across multiple pathology dense prediction tasks. The advantage is particularly pronounced under limited annotation settings, where CMD exhibits stronger robustness and generalization ability. Our findings suggest that purely convolutional architectures can also serve as competitive pathology foundation models for cell-level dense prediction, achieving leading performance within the current ViT-dominated paradigm and providing a scalable, high-performance solution that better preserves histological structural priors for fine-grained pathology understanding.

Immunohistochemical (IHC) staining highlights the molecular information critical to diagnostics in tissue samples. However, compared to H&E staining, IHC staining can be much more expensive in terms of both labor and the laboratory equipment required. This motivates recent research that demonstrates that the correlations between the morphological information present in the H&E-stained slides and the molecular information in the IHC-stained slides can be used for H&E-to-IHC stain translation. However, due to a lack of pixel-perfect H&E-IHC groundtruth pairs, most existing methods have resorted to relying on expert annotations. To remedy this situation, we present a new loss function, Adaptive Supervised PatchNCE (ASP), to directly deal with the input to target inconsistencies in a proposed H&E-to-IHC image-to-image translation framework. The ASP loss is built upon a patch-based contrastive learning criterion, named Supervised PatchNCE (SP), and augments it further with weight scheduling to mitigate the negative impact of noisy supervision. Lastly, we introduce the Multi-IHC Stain Translation (MIST) dataset, which contains aligned H&E-IHC patches for 4 different IHC stains critical to breast cancer diagnosis. In our experiment, we demonstrate that our proposed method outperforms existing image-to-image translation methods for stain translation to multiple IHC stains. All of our code and datasets are available at https://github.com/lifangda01/AdaptiveSupervisedPatchNCE.

The recent surge in performance for image analysis of digitised pathology slides can largely be attributed to the advances in deep learning. Deep models can be used to initially localise various structures in the tissue and hence facilitate the extraction of interpretable features for biomarker discovery. However, these models are typically trained for a single task and therefore scale poorly as we wish to adapt the model for an increasing number of different tasks. Also, supervised deep learning models are very data hungry and therefore rely on large amounts of training data to perform well. In this paper, we present a multi-task learning approach for segmentation and classification of nuclei, glands, lumina and different tissue regions that leverages data from multiple independent data sources. While ensuring that our tasks are aligned by the same tissue type and resolution, we enable meaningful simultaneous prediction with a single network. As a result of feature sharing, we also show that the learned representation can be used to improve the performance of additional tasks via transfer learning, including nuclear classification and signet ring cell detection. As part of this work, we train our developed Cerberus model on a huge amount of data, consisting of over 600K objects for segmentation and 440K patches for classification. We use our approach to process 599 colorectal whole-slide images from TCGA, where we localise 377 million, 900K and 2.1 million nuclei, glands and lumina, respectively and make the results available to the community for downstream analysis.

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.

Histopathology image analysis is fundamental to digital pathology, with hematoxylin and eosin (H&E) staining as the gold standard for diagnostic and prognostic assessments. While H&E imaging effectively highlights cellular and tissue structures, it lacks sensitivity to birefringence and tissue anisotropy, which are crucial for assessing collagen organization, fiber alignment, and microstructural alterations--key indicators of tumor progression, fibrosis, and other pathological conditions. To bridge this gap, we construct a polarization imaging system and curate a new dataset of over 13,000 paired Polar-H&E images. Visualizations of polarization properties reveal distinctive optical signatures in pathological tissues, underscoring its diagnostic value. Building on this dataset, we propose PolarHE, a dual-modality fusion framework that integrates H&E with polarization imaging, leveraging the latter ability to enhance tissue characterization. Our approach employs a feature decomposition strategy to disentangle common and modality specific features, ensuring effective multimodal representation learning. Through comprehensive validation, our approach significantly outperforms previous methods, achieving an accuracy of 86.70% on the Chaoyang dataset and 89.06% on the MHIST dataset. These results demonstrate that polarization imaging is a powerful and underutilized modality in computational pathology, enriching feature representation and improving diagnostic accuracy. PolarHE establishes a promising direction for multimodal learning, paving the way for more interpretable and generalizable pathology models.

Multimodal pathology-genomic analysis is critical for cancer survival prediction. However, existing approaches predominantly integrate formalin-fixed paraffin-embedded (FFPE) slides with genomic data, while neglecting the availability of other preservation slides, such as Fresh Froze (FF) slides. Moreover, as the high-resolution spatial nature of pathology data tends to dominate the cross-modality fusion process, it hinders effective multimodal fusion and leads to modality imbalance challenges between pathology and genomics. These methods also typically require complete data modalities, limiting their clinical applicability with incomplete modalities, such as missing either pathology or genomic data. In this paper, we propose a multimodal survival prediction framework that leverages hypergraph learning to effectively integrate multi-WSI information and cross-modality interactions between pathology slides and genomics data while addressing modality imbalance. In addition, we introduce a memory mechanism that stores previously learned paired pathology-genomic features and dynamically compensates for incomplete modalities. Experiments on five TCGA datasets demonstrate that our model outperforms advanced methods by over 2.3% in C-Index. Under incomplete modality scenarios, our approach surpasses pathology-only (3.3%) and gene-only models (7.9%). Code: https://github.com/MCPathology/M2Surv

Whole slide imaging (WSI) has transformed digital pathology by enabling computational analysis of gigapixel histopathology images. Recent foundation model advances have accelerated progress in computational pathology, facilitating joint reasoning across pathology images, clinical reports, and structured data. Despite this progress, challenges remain: the extreme resolution of WSIs creates computational hurdles for visual learning; limited expert annotations constrain supervised approaches; integrating multimodal information while preserving biological interpretability remains difficult; and the opacity of modeling ultra-long visual sequences hinders clinical transparency. This review comprehensively surveys recent advances in multimodal computational pathology. We systematically analyze four research directions: (1) self-supervised representation learning and structure-aware token compression for WSIs; (2) multimodal data generation and augmentation; (3) parameter-efficient adaptation and reasoning-enhanced few-shot learning; and (4) multi-agent collaborative reasoning for trustworthy diagnosis. We specifically examine how token compression enables cross-scale modeling and how multi-agent mechanisms simulate a pathologist's "Chain of Thought" across magnifications to achieve uncertainty-aware evidence fusion. Finally, we discuss open challenges and argue that future progress depends on unified multimodal frameworks integrating high-resolution visual data with clinical and biomedical knowledge to support interpretable and safe AI-assisted diagnosis.

Recent rapid progress in the field of computational pathology has been enabled by foundation models. These models are beginning to move beyond encoding image patches towards whole-slide understanding but their clinical utility remains limited. In this work, we present PRISM2, a multimodal slide-level foundation model trained on data from 700,000 diagnostic specimen-report pairs, the largest vision (2.3 million whole slide images) and language (14M question-answer pairs) histopathology dataset to date. By learning through clinical-dialogue supervision, PRISM2 aligns histomorphologic features with the language of diagnostic reasoning, producing slide-level representations that support both direct diagnostic question-answering and transferable embeddings for downstream tasks. Without additional training, PRISM2 matches or exceeds the cancer-detection performance of clinical-grade products. This is observed without loss of generality on other tasks, where PRISM2 achieves top performance. Finally, using survival prediction as the example, we show that task-specific finetuning with a large dataset can outperform task-specific models, further improving performance. These results demonstrate how language-supervised pretraining provides a scalable, clinically grounded signal for learning generalizable pathology representations, bridging human diagnostic reasoning and foundation-model performance.

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 LMMs. It comprises 33,573 multimodal multi-choice questions and 21,599 images from various sources, and an explanation for the correct answer accompanies each question. The construction of PathMMU capitalizes on the robust capabilities of GPT-4V, utilizing approximately 30,000 gathered image-caption pairs to generate Q\&As. Significantly, to maximize PathMMU's authority, we invite six 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 three 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 51.7\% zero-shot performance, significantly lower than the 71.4\% demonstrated by human pathologists. After fine-tuning, even open-sourced LMMs can surpass GPT-4V with a performance of over 60\%, 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 LLMs for pathology.

The emerging area of computational pathology (CPath) is ripe ground for the application of deep learning (DL) methods to healthcare due to the sheer volume of raw pixel data in whole-slide images (WSIs) of cancerous tissue slides. However, it is imperative for the DL algorithms relying on nuclei-level details to be able to cope with data from `the clinical wild', which tends to be quite challenging. We study, and extend recently released PanNuke dataset consisting of ~200,000 nuclei categorized into 5 clinically important classes for the challenging tasks of segmenting and classifying nuclei in WSIs. Previous pan-cancer datasets consisted of only up to 9 different tissues and up to 21,000 unlabeled nuclei and just over 24,000 labeled nuclei with segmentation masks. PanNuke consists of 19 different tissue types that have been semi-automatically annotated and quality controlled by clinical pathologists, leading to a dataset with statistics similar to the clinical wild and with minimal selection bias. We study the performance of segmentation and classification models when applied to the proposed dataset and demonstrate the application of models trained on PanNuke to whole-slide images. We provide comprehensive statistics about the dataset and outline recommendations and research directions to address the limitations of existing DL tools when applied to real-world CPath applications.

Pathology Foundation Models (FMs) have shown strong performance across a wide range of pathology image representation and diagnostic tasks. However, FMs do not exhibit the expected performance advantage over traditional specialized models in Nuclei Detection and Classification (NDC). In this work, we reveal that jointly optimizing nuclei detection and classification leads to severe representation degradation in FMs. Moreover, we identify that the substantial intrinsic disparity in task difficulty between nuclei detection and nuclei classification renders joint NDC optimization unnecessarily computationally burdensome for the detection stage. To address these challenges, we propose DeNuC, a simple yet effective method designed to break through existing bottlenecks by Decoupling Nuclei detection and Classification. DeNuC employs a lightweight model for accurate nuclei localization, subsequently leveraging a pathology FM to encode input images and query nucleus-specific features based on the detected coordinates for classification. Extensive experiments on three widely used benchmarks demonstrate that DeNuC effectively unlocks the representational potential of FMs for NDC and significantly outperforms state-of-the-art methods. Notably, DeNuC improves F1 scores by 4.2% and 3.6% (or higher) on the BRCAM2C and PUMA datasets, respectively, while using only 16% (or fewer) trainable parameters compared to other methods. Code is available at https://github.com/ZijiangY1116/DeNuC.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

Extraction of relevant pathological terms from radiology reports is important for correct image label generation and disease population studies. In this letter, we compare the performance of some known application program interface (APIs) for the task of thoracic abnormality extraction from radiology reports. We explored several medical domain specific annotation tools like Medical Text Indexer(MTI) with Non-MEDLINE and Mesh On Demand(MOD) options and generic Natural Language Understanding (NLU) API provided by the IBM cloud. Our results show that although MTI and MOD are intended for extracting medical terms, their performance is worst compared to generic extraction API like IBM NLU. Finally, we trained a DNN-based Named Entity Recognition (NER) model to extract the key concept words from radiology reports. Our model outperforms the medical specific and generic API performance by a large margin. Our results demonstrate the inadequacy of generic APIs for pathology extraction task and establish the importance of domain specific model training for improved results. We hope that these results motivate the research community to release larger de-identified radiology reports corpus for building high accuracy machine learning models for the important task of pathology extraction.

Identifying disease phenotypes from electronic health records (EHRs) is critical for numerous secondary uses. Manually encoding physician knowledge into rules is particularly challenging for rare diseases due to inadequate EHR coding, necessitating review of clinical notes. Large language models (LLMs) offer promise in text understanding but may not efficiently handle real-world clinical documentation. We propose a zero-shot LLM-based method enriched by retrieval-augmented generation and MapReduce, which pre-identifies disease-related text snippets to be used in parallel as queries for the LLM to establish diagnosis. We show that this method as applied to pulmonary hypertension (PH), a rare disease characterized by elevated arterial pressures in the lungs, significantly outperforms physician logic rules (F_1 score of 0.62 vs. 0.75). This method has the potential to enhance rare disease cohort identification, expanding the scope of robust clinical research and care gap identification.

The visual examination of tissue biopsy sections is fundamental for cancer diagnosis, with pathologists analyzing sections at multiple magnifications to discern tumor cells and their subtypes. However, existing attention-based multiple instance learning (MIL) models, used for analyzing Whole Slide Images (WSIs) in cancer diagnostics, often overlook the contextual information of tumor and neighboring tiles, leading to misclassifications. To address this, we propose the Context-Aware Multiple Instance Learning (CAMIL) architecture. CAMIL incorporates neighbor-constrained attention to consider dependencies among tiles within a WSI and integrates contextual constraints as prior knowledge into the MIL model. We evaluated CAMIL on subtyping non-small cell lung cancer (TCGA-NSCLC) and detecting lymph node (CAMELYON16) metastasis, achieving test AUCs of 0.959\% and 0.975\%, respectively, outperforming other state-of-the-art methods. Additionally, CAMIL enhances model interpretability by identifying regions of high diagnostic value.

Digitizing pathological images into gigapixel Whole Slide Images (WSIs) has opened new avenues for Computational Pathology (CPath). As positive tissue comprises only a small fraction of gigapixel WSIs, existing Multiple Instance Learning (MIL) methods typically focus on identifying salient instances via attention mechanisms. However, this leads to a bias towards easy-to-classify instances while neglecting challenging ones. Recent studies have shown that hard examples are crucial for accurately modeling discriminative boundaries. Applying such an idea at the instance level, we elaborate a novel MIL framework with masked hard instance mining (MHIM-MIL), which utilizes a Siamese structure with a consistency constraint to explore the hard instances. Using a class-aware instance probability, MHIM-MIL employs a momentum teacher to mask salient instances and implicitly mine hard instances for training the student model. To obtain diverse, non-redundant hard instances, we adopt large-scale random masking while utilizing a global recycle network to mitigate the risk of losing key features. Furthermore, the student updates the teacher using an exponential moving average, which identifies new hard instances for subsequent training iterations and stabilizes optimization. Experimental results on cancer diagnosis, subtyping, survival analysis tasks, and 12 benchmarks demonstrate that MHIM-MIL outperforms the latest methods in both performance and efficiency. The code is available at: https://github.com/DearCaat/MHIM-MIL.

Recent advances in multi-modal algorithms have driven and been driven by the increasing availability of large image-text datasets, leading to significant strides in various fields, including computational pathology. However, in most existing medical image-text datasets, the text typically provides high-level summaries that may not sufficiently describe sub-tile regions within a large pathology image. For example, an image might cover an extensive tissue area containing cancerous and healthy regions, but the accompanying text might only specify that this image is a cancer slide, lacking the nuanced details needed for in-depth analysis. In this study, we introduce STimage-1K4M, a novel dataset designed to bridge this gap by providing genomic features for sub-tile images. STimage-1K4M contains 1,149 images derived from spatial transcriptomics data, which captures gene expression information at the level of individual spatial spots within a pathology image. Specifically, each image in the dataset is broken down into smaller sub-image tiles, with each tile paired with 15,000-30,000 dimensional gene expressions. With 4,293,195 pairs of sub-tile images and gene expressions, STimage-1K4M offers unprecedented granularity, paving the way for a wide range of advanced research in multi-modal data analysis an innovative applications in computational pathology, and beyond.

Histopathology has played an essential role in cancer diagnosis. With the rapid advances in convolutional neural networks (CNN). Various CNN-based automated pathological image segmentation approaches have been developed in computer-assisted pathological image analysis. In the past few years, Transformer neural networks (Transformer) have shown the unique merit of capturing the global long-distance dependencies across the entire image as a new deep learning paradigm. Such merit is appealing for exploring spatially heterogeneous pathological images. However, there have been very few, if any, studies that have systematically evaluated the current Transformer-based approaches in pathological image segmentation. To assess the performance of Transformer segmentation models on whole slide images (WSI), we quantitatively evaluated six prevalent transformer-based models on tumor segmentation, using the widely used PAIP liver histopathological dataset. For a more comprehensive analysis, we also compare the transformer-based models with six major traditional CNN-based models. The results show that the Transformer-based models exhibit a general superior performance over the CNN-based models. In particular, Segmenter, Swin-Transformer and TransUNet-all transformer-based-came out as the best performers among the twelve evaluated models.

Developing self-supervised learning (SSL) models that can learn universal and transferable representations of H&E gigapixel whole-slide images (WSIs) is becoming increasingly valuable in computational pathology. These models hold the potential to advance critical tasks such as few-shot classification, slide retrieval, and patient stratification. Existing approaches for slide representation learning extend the principles of SSL from small images (e.g., 224 x 224 patches) to entire slides, usually by aligning two different augmentations (or views) of the slide. Yet the resulting representation remains constrained by the limited clinical and biological diversity of the views. Instead, we postulate that slides stained with multiple markers, such as immunohistochemistry, can be used as different views to form a rich task-agnostic training signal. To this end, we introduce Madeleine, a multimodal pretraining strategy for slide representation learning. Madeleine is trained with a dual global-local cross-stain alignment objective on large cohorts of breast cancer samples (N=4,211 WSIs across five stains) and kidney transplant samples (N=12,070 WSIs across four stains). We demonstrate the quality of slide representations learned by Madeleine on various downstream evaluations, ranging from morphological and molecular classification to prognostic prediction, comprising 21 tasks using 7,299 WSIs from multiple medical centers. Code is available at https://github.com/mahmoodlab/MADELEINE.

As deep learning models gain attraction in medical data, ensuring transparent and trustworthy decision-making is essential. In skin cancer diagnosis, while advancements in lesion detection and classification have improved accuracy, the black-box nature of these methods poses challenges in understanding their decision processes, leading to trust issues among physicians. This study leverages the CLIP (Contrastive Language-Image Pretraining) model, trained on different skin lesion datasets, to capture meaningful relationships between visual features and diagnostic criteria terms. To further enhance transparency, we propose a method called MedGrad E-CLIP, which builds on gradient-based E-CLIP by incorporating a weighted entropy mechanism designed for complex medical imaging like skin lesions. This approach highlights critical image regions linked to specific diagnostic descriptions. The developed integrated pipeline not only classifies skin lesions by matching corresponding descriptions but also adds an essential layer of explainability developed especially for medical data. By visually explaining how different features in an image relates to diagnostic criteria, this approach demonstrates the potential of advanced vision-language models in medical image analysis, ultimately improving transparency, robustness, and trust in AI-driven diagnostic systems.

Rare cancers comprise 20-25% of all malignancies but face major diagnostic challenges due to limited expert availability-especially in pediatric oncology, where they represent over 70% of cases. While pathology vision-language (VL) foundation models show promising zero-shot capabilities for common cancer subtyping, their clinical performance for rare cancers remains limited. Existing multi-instance learning (MIL) methods rely only on visual features, overlooking cross-modal knowledge and compromising interpretability critical for rare cancer diagnosis. To address this limitation, we propose PathPT, a novel framework that fully exploits the potential of vision-language pathology foundation models through spatially-aware visual aggregation and task-specific prompt tuning. Unlike conventional MIL, PathPT converts WSI-level supervision into fine-grained tile-level guidance by leveraging the zero-shot capabilities of VL models, thereby preserving localization on cancerous regions and enabling cross-modal reasoning through prompts aligned with histopathological semantics. We benchmark PathPT on eight rare cancer datasets(four adult and four pediatric) spanning 56 subtypes and 2,910 WSIs, as well as three common cancer datasets, evaluating four state-of-the-art VL models and four MIL frameworks under three few-shot settings. Results show that PathPT consistently delivers superior performance, achieving substantial gains in subtyping accuracy and cancerous region grounding ability. This work advances AI-assisted diagnosis for rare cancers, offering a scalable solution for improving subtyping accuracy in settings with limited access to specialized expertise.

Computational pathology needs whole-slide image (WSI) foundation models that transfer across diverse clinical tasks, yet current approaches remain largely slide-centric, often depend on private data and expensive paired-report supervision, and do not explicitly model relationships among multiple slides from the same patient. We present MOOZY, a patient-first pathology foundation model in which the patient case, not the individual slide, is the core unit of representation. MOOZY explicitly models dependencies across all slides from the same patient via a case transformer during pretraining, combining multi-stage open self-supervision with scaled low-cost task supervision. In Stage 1, we pretrain a vision-only slide encoder on 77,134 public slide feature grids using masked self-distillation. In Stage 2, we align these representations with clinical semantics using a case transformer and multi-task supervision over 333 tasks from 56 public datasets, including 205 classification and 128 survival tasks across four endpoints. Across eight held-out tasks with five-fold frozen-feature probe evaluation, MOOZY achieves best or tied-best performance on most metrics and improves macro averages over TITAN by +7.37%, +5.50%, and +7.83% and over PRISM by +8.83%, +10.70%, and +9.78% for weighted F1, weighted ROC-AUC, and balanced accuracy, respectively. MOOZY is also parameter efficient with 85.77M parameters, 14x smaller than GigaPath. These results demonstrate that open, reproducible patient-level pretraining yields transferable embeddings, providing a practical path toward scalable patient-first histopathology foundation models.

The tumor immune microenvironment (TIME) in non-small cell lung cancer (NSCLC) histopathology contains morphological and molecular characteristics predictive of immunotherapy response. Computational quantification of TIME characteristics, such as cell detection and tissue segmentation, can support biomarker development. However, currently available digital pathology datasets of NSCLC for the development of cell detection or tissue segmentation algorithms are limited in scope, lack annotations of clinically prevalent metastatic sites, and forgo molecular information such as PD-L1 immunohistochemistry (IHC). To fill this gap, we introduce the IGNITE data toolkit, a multi-stain, multi-centric, and multi-scanner dataset of annotated NSCLC whole-slide images. We publicly release 887 fully annotated regions of interest from 155 unique patients across three complementary tasks: (i) multi-class semantic segmentation of tissue compartments in H&E-stained slides, with 16 classes spanning primary and metastatic NSCLC, (ii) nuclei detection, and (iii) PD-L1 positive tumor cell detection in PD-L1 IHC slides. To the best of our knowledge, this is the first public NSCLC dataset with manual annotations of H&E in metastatic sites and PD-L1 IHC.

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.

Representation learning of pathology whole-slide images (WSIs) has primarily relied on weak supervision with Multiple Instance Learning (MIL). This approach leads to slide representations highly tailored to a specific clinical task. Self-supervised learning (SSL) has been successfully applied to train histopathology foundation models (FMs) for patch embedding generation. However, generating patient or slide level embeddings remains challenging. Existing approaches for slide representation learning extend the principles of SSL from patch level learning to entire slides by aligning different augmentations of the slide or by utilizing multimodal data. By integrating tile embeddings from multiple FMs, we propose a new single modality SSL method in feature space that generates useful slide representations. Our contrastive pretraining strategy, called COBRA, employs multiple FMs and an architecture based on Mamba-2. COBRA exceeds performance of state-of-the-art slide encoders on four different public CPTAC cohorts on average by at least +3.8% AUC, despite only being pretrained on 3048 WSIs from TCGA. Additionally, COBRA is readily compatible at inference time with previously unseen feature extractors.

In clinical radiology reports, doctors capture important information about the patient's health status. They convey their observations from raw medical imaging data about the inner structures of a patient. As such, formulating reports requires medical experts to possess wide-ranging knowledge about anatomical regions with their normal, healthy appearance as well as the ability to recognize abnormalities. This explicit grasp on both the patient's anatomy and their appearance is missing in current medical image-processing systems as annotations are especially difficult to gather. This renders the models to be narrow experts e.g. for identifying specific diseases. In this work, we recover this missing link by adding human anatomy into the mix and enable the association of content in medical reports to their occurrence in associated imagery (medical phrase grounding). To exploit anatomical structures in this scenario, we present a sophisticated automatic pipeline to gather and integrate human bodily structures from computed tomography datasets, which we incorporate in our PAXRay: A Projected dataset for the segmentation of Anatomical structures in X-Ray data. Our evaluation shows that methods that take advantage of anatomical information benefit heavily in visually grounding radiologists' findings, as our anatomical segmentations allow for up to absolute 50% better grounding results on the OpenI dataset as compared to commonly used region proposals. The PAXRay dataset is available at https://constantinseibold.github.io/paxray/.

Visual Language Models (VLMs) have demonstrated impressive capabilities in visual grounding tasks. However, their effectiveness in the medical domain, particularly for abnormality detection and localization within medical images, remains underexplored. A major challenge is the complex and abstract nature of medical terminology, which makes it difficult to directly associate pathological anomaly terms with their corresponding visual features. In this work, we introduce a novel approach to enhance VLM performance in medical abnormality detection and localization by leveraging decomposed medical knowledge. Instead of directly prompting models to recognize specific abnormalities, we focus on breaking down medical concepts into fundamental attributes and common visual patterns. This strategy promotes a stronger alignment between textual descriptions and visual features, improving both the recognition and localization of abnormalities in medical images.We evaluate our method on the 0.23B Florence-2 base model and demonstrate that it achieves comparable performance in abnormality grounding to significantly larger 7B LLaVA-based medical VLMs, despite being trained on only 1.5% of the data used for such models. Experimental results also demonstrate the effectiveness of our approach in both known and previously unseen abnormalities, suggesting its strong generalization capabilities.

Deep learning has enabled the development of highly robust foundation models for various pathological tasks across diverse diseases and patient cohorts. Among these models, vision-language pre-training, which leverages large-scale paired data to align pathology image and text embedding spaces, and provides a novel zero-shot paradigm for downstream tasks. However, existing models have been primarily data-driven and lack the incorporation of domain-specific knowledge, which limits their performance in cancer diagnosis, especially for rare tumor subtypes. To address this limitation, we establish a Knowledge-enhanced Pathology (KEEP) foundation model that harnesses disease knowledge to facilitate vision-language pre-training. Specifically, we first construct a disease knowledge graph (KG) that covers 11,454 human diseases with 139,143 disease attributes, including synonyms, definitions, and hypernym relations. We then systematically reorganize the millions of publicly available noisy pathology image-text pairs, into 143K well-structured semantic groups linked through the hierarchical relations of the disease KG. To derive more nuanced image and text representations, we propose a novel knowledge-enhanced vision-language pre-training approach that integrates disease knowledge into the alignment within hierarchical semantic groups instead of unstructured image-text pairs. Validated on 18 diverse benchmarks with more than 14,000 whole slide images (WSIs), KEEP achieves state-of-the-art performance in zero-shot cancer diagnostic tasks. Notably, for cancer detection, KEEP demonstrates an average sensitivity of 89.8% at a specificity of 95.0% across 7 cancer types. For cancer subtyping, KEEP achieves a median balanced accuracy of 0.456 in subtyping 30 rare brain cancers, indicating strong generalizability for diagnosing rare tumors.

Whole Slide Images (WSIs) exhibit hierarchical structure, where diagnostic information emerges from cellular morphology, regional tissue organization, and global context. Existing Computational Pathology (CPath) Multimodal Large Language Models (MLLMs) typically compress an entire WSI into a single embedding, which hinders fine-grained grounding and ignores how pathologists synthesize evidence across different scales. We introduce MLLM-HWSI, a Hierarchical WSI-level MLLM that aligns visual features with pathology language at four distinct scales, cell as word, patch as phrase, region as sentence, and WSI as paragraph to support interpretable evidence-grounded reasoning. MLLM-HWSI decomposes each WSI into multi-scale embeddings with scale-specific projectors and jointly enforces (i) a hierarchical contrastive objective and (ii) a cross-scale consistency loss, preserving semantic coherence from cells to the WSI. We compute diagnostically relevant patches and aggregate segmented cell embeddings into a compact cellular token per-patch using a lightweight Cell-Cell Attention Fusion (CCAF) transformer. The projected multi-scale tokens are fused with text tokens and fed to an instruction-tuned LLM for open-ended reasoning, VQA, report, and caption generation tasks. Trained in three stages, MLLM-HWSI achieves new SOTA results on 13 WSI-level benchmarks across six CPath tasks. By aligning language with multi-scale visual evidence, MLLM-HWSI provides accurate, interpretable outputs that mirror diagnostic workflows and advance holistic WSI understanding. Code is available at: https://github.com/BasitAlawode/HWSI-MLLM{GitHub}.

Timely and accurate lymphoma diagnosis is essential for guiding cancer treatment. Standard diagnostic practice combines hematoxylin and eosin (HE)-stained whole slide images with immunohistochemistry, flow cytometry, and molecular genetic tests to determine lymphoma subtypes, a process requiring costly equipment, skilled personnel, and causing treatment delays. Deep learning methods could assist pathologists by extracting diagnostic information from routinely available HE-stained slides, yet comprehensive benchmarks for lymphoma subtyping on multicenter data are lacking. In this work, we present the first multicenter lymphoma benchmarking dataset covering four common lymphoma subtypes and healthy control tissue. We systematically evaluate five publicly available pathology foundation models (H-optimus-1, H0-mini, Virchow2, UNI2, Titan) combined with attention-based (AB-MIL) and transformer-based (TransMIL) multiple instance learning aggregators across three magnifications (10x, 20x, 40x). On in-distribution test sets, models achieve multiclass balanced accuracies exceeding 80% across all magnifications, with all foundation models performing similarly and both aggregation methods showing comparable results. The magnification study reveals that 40x resolution is sufficient, with no performance gains from higher resolutions or cross-magnification aggregation. However, on out-of-distribution test sets, performance drops substantially to around 60%, highlighting significant generalization challenges. To advance the field, larger multicenter studies covering additional rare lymphoma subtypes are needed. We provide an automated benchmarking pipeline to facilitate such future research.

Task-specific deep learning models in histopathology offer promising opportunities for improving diagnosis, clinical research, and precision medicine. However, development of such models is often limited by availability of high-quality data. Foundation models in histopathology that learn general representations across a wide range of tissue types, diagnoses, and magnifications offer the potential to reduce the data, compute, and technical expertise necessary to develop task-specific deep learning models with the required level of model performance. In this work, we describe the development and evaluation of foundation models for histopathology via self-supervised learning (SSL). We first establish a diverse set of benchmark tasks involving 17 unique tissue types and 12 unique cancer types and spanning different optimal magnifications and task types. Next, we use this benchmark to explore and evaluate histopathology-specific SSL methods followed by further evaluation on held out patch-level and weakly supervised tasks. We found that standard SSL methods thoughtfully applied to histopathology images are performant across our benchmark tasks and that domain-specific methodological improvements can further increase performance. Our findings reinforce the value of using domain-specific SSL methods in pathology, and establish a set of high quality foundation models to enable further research across diverse applications.

The in-vivo identification of the kidney stone types during an ureteroscopy would be a major medical advance in urology, as it could reduce the time of the tedious renal calculi extraction process, while diminishing infection risks. Furthermore, such an automated procedure would make possible to prescribe anti-recurrence treatments immediately. Nowadays, only few experienced urologists are able to recognize the kidney stone types in the images of the videos displayed on a screen during the endoscopy. Thus, several deep learning (DL) models have recently been proposed to automatically recognize the kidney stone types using ureteroscopic images. However, these DL models are of black box nature whicl limits their applicability in clinical settings. This contribution proposes a case-based reasoning DL model which uses prototypical parts (PPs) and generates local and global descriptors. The PPs encode for each class (i.e., kidney stone type) visual feature information (hue, saturation, intensity and textures) similar to that used by biologists. The PPs are optimally generated due a new loss function used during the model training. Moreover, the local and global descriptors of PPs allow to explain the decisions ("what" information, "where in the images") in an understandable way for biologists and urologists. The proposed DL model has been tested on a database including images of the six most widespread kidney stone types. The overall average classification accuracy was 90.37. When comparing this results with that of the eight other DL models of the kidney stone state-of-the-art, it can be seen that the valuable gain in explanability was not reached at the expense of accuracy which was even slightly increased with respect to that (88.2) of the best method of the literature. These promising and interpretable results also encourage urologists to put their trust in AI-based solutions.

Objective: To enhance automated de-identification of radiology reports by scaling transformer-based models through extensive training datasets and benchmarking performance against commercial cloud vendor systems for protected health information (PHI) detection. Materials and Methods: In this retrospective study, we built upon a state-of-the-art, transformer-based, PHI de-identification pipeline by fine-tuning on two large annotated radiology corpora from Stanford University, encompassing chest X-ray, chest CT, abdomen/pelvis CT, and brain MR reports and introducing an additional PHI category (AGE) into the architecture. Model performance was evaluated on test sets from Stanford and the University of Pennsylvania (Penn) for token-level PHI detection. We further assessed (1) the stability of synthetic PHI generation using a "hide-in-plain-sight" method and (2) performance against commercial systems. Precision, recall, and F1 scores were computed across all PHI categories. Results: Our model achieved overall F1 scores of 0.973 on the Penn dataset and 0.996 on the Stanford dataset, outperforming or maintaining the previous state-of-the-art model performance. Synthetic PHI evaluation showed consistent detectability (overall F1: 0.959 [0.958-0.960]) across 50 independently de-identified Penn datasets. Our model outperformed all vendor systems on synthetic Penn reports (overall F1: 0.960 vs. 0.632-0.754). Discussion: Large-scale, multimodal training improved cross-institutional generalization and robustness. Synthetic PHI generation preserved data utility while ensuring privacy. Conclusion: A transformer-based de-identification model trained on diverse radiology datasets outperforms prior academic and commercial systems in PHI detection and establishes a new benchmark for secure clinical text processing.

Pathological images are inherently multi-scale, requiring pathologists to integrate evidence from global tissue architecture at low magnification to cellular morphology at higher magnification for accurate diagnosis. While existing pathological datasets for vision-language models (VLMs) include various scales, they often lack explicit cross-scale reasoning objectives. This limitation prevents VLMs from capturing essential cross-scale representations and learning evidence-based reasoning. To bridge this gap, we introduce the first cross-scale training and evaluation paradigm that formulates pathology interpretation as multi-magnification reasoning. However, creating such a task reveals a critical challenge: multi-image visual question answering (VQA) is prone to text-only shortcuts, which allow models to guess answers using magnification-dependent artifacts rather than visual evidence. To address this, we propose a leakage-aware curation pipeline that combines adversarial text-only screening with constraint-guided question design. Using this pipeline, we construct Scale-VQA, a high-quality benchmark with 4,685 multiple-choice questions grounded in 2,537 pathology images across multiple magnification levels. Finally, we present ScaleReasoner-R1, a model trained via reinforcement learning to optimize performance on cross-scale VQA tasks. ScaleReasoner-R1 achieves state-of-the-art performance on our cross-scale reasoning benchmark and generalizes to SOTA performance on established single-scale benchmarks. Findings suggest that even the limited cross-scale supervision can significantly improve pathological understanding. Code is available at https://github.com/iMVR-PL/ScaleReasoner-R1.

Large Multimodal Models (LMMs) have shown remarkable progress in the field of medical Visual Question Answering (Med-VQA), achieving high accuracy on existing benchmarks. However, their reliability under robust evaluation is questionable. This study reveals that state-of-the-art models, when subjected to simple probing evaluation, perform worse than random guessing on medical diagnosis questions. To address this critical evaluation problem, we introduce the Probing Evaluation for Medical Diagnosis (ProbMed) dataset to rigorously assess LMM performance in medical imaging through probing evaluation and procedural diagnosis. Particularly, probing evaluation features pairing original questions with negation questions with hallucinated attributes, while procedural diagnosis requires reasoning across various diagnostic dimensions for each image, including modality recognition, organ identification, clinical findings, abnormalities, and positional grounding. Our evaluation reveals that top-performing models like GPT-4V and Gemini Pro perform worse than random guessing on specialized diagnostic questions, indicating significant limitations in handling fine-grained medical inquiries. Besides, models like LLaVA-Med struggle even with more general questions, and results from CheXagent demonstrate the transferability of expertise across different modalities of the same organ, showing that specialized domain knowledge is still crucial for improving performance. This study underscores the urgent need for more robust evaluation to ensure the reliability of LMMs in critical fields like medical diagnosis, and current LMMs are still far from applicable to those fields.

Recent accelerations in multi-modal applications have been made possible with the plethora of image and text data available online. However, the scarcity of analogous data in the medical field, specifically in histopathology, has halted comparable progress. To enable similar representation learning for histopathology, we turn to YouTube, an untapped resource of videos, offering 1,087 hours of valuable educational histopathology videos from expert clinicians. From YouTube, we curate Quilt: a large-scale vision-language dataset consisting of 768,826 image and text pairs. Quilt was automatically curated using a mixture of models, including large language models, handcrafted algorithms, human knowledge databases, and automatic speech recognition. In comparison, the most comprehensive datasets curated for histopathology amass only around 200K samples. We combine Quilt with datasets from other sources, including Twitter, research papers, and the internet in general, to create an even larger dataset: Quilt-1M, with 1M paired image-text samples, marking it as the largest vision-language histopathology dataset to date. We demonstrate the value of Quilt-1M by fine-tuning a pre-trained CLIP model. Our model outperforms state-of-the-art models on both zero-shot and linear probing tasks for classifying new histopathology images across 13 diverse patch-level datasets of 8 different sub-pathologies and cross-modal retrieval tasks.

In recent years, the advent of foundation models (FM) for digital pathology has relied heavily on scaling the pre-training datasets and the model size, yielding large and powerful models. While it resulted in improving the performance on diverse downstream tasks, it also introduced increased computational cost and inference time. In this work, we explore the distillation of a large foundation model into a smaller one, reducing the number of parameters by several orders of magnitude. Leveraging distillation techniques, our distilled model, H0-mini, achieves nearly comparable performance to large FMs at a significantly reduced inference cost. It is evaluated on several public benchmarks, achieving 3rd place on the HEST benchmark and 5th place on the EVA benchmark. Additionally, a robustness analysis conducted on the PLISM dataset demonstrates that our distilled model reaches excellent robustness to variations in staining and scanning conditions, significantly outperforming other state-of-the art models. This opens new perspectives to design lightweight and robust models for digital pathology, without compromising on performance.

Driven by the recent advances in deep learning methods and, in particular, by the development of modern self-supervised learning algorithms, increased interest and efforts have been devoted to build foundation models (FMs) for medical images. In this work, we present our scalable training pipeline for large pathology imaging data, and a comprehensive analysis of various hyperparameter choices and training techniques for building pathology FMs. We release and make publicly available the first batch of our pathology FMs (https://github.com/kaiko-ai/towards_large_pathology_fms) trained on open-access TCGA whole slide images, a commonly used collection of pathology images. The experimental evaluation shows that our models reach state-of-the-art performance on various patch-level downstream tasks, ranging from breast cancer subtyping to colorectal nuclear segmentation. Finally, to unify the evaluation approaches used in the field and to simplify future comparisons of different FMs, we present an open-source framework (https://github.com/kaiko-ai/eva) designed for the consistent evaluation of pathology FMs across various downstream tasks.

This paper addresses complex challenges in histopathological image analysis through three key contributions. Firstly, it introduces a fast patch selection method, FPS, for whole-slide image (WSI) analysis, significantly reducing computational cost while maintaining accuracy. Secondly, it presents PathDino, a lightweight histopathology feature extractor with a minimal configuration of five Transformer blocks and only 9 million parameters, markedly fewer than alternatives. Thirdly, it introduces a rotation-agnostic representation learning paradigm using self-supervised learning, effectively mitigating overfitting. We also show that our compact model outperforms existing state-of-the-art histopathology-specific vision transformers on 12 diverse datasets, including both internal datasets spanning four sites (breast, liver, skin, and colorectal) and seven public datasets (PANDA, CAMELYON16, BRACS, DigestPath, Kather, PanNuke, and WSSS4LUAD). Notably, even with a training dataset of 6 million histopathology patches from The Cancer Genome Atlas (TCGA), our approach demonstrates an average 8.5% improvement in patch-level majority vote performance. These contributions provide a robust framework for enhancing image analysis in digital pathology, rigorously validated through extensive evaluation. Project Page: https://rhazeslab.github.io/PathDino-Page/

Rare diseases, including Inborn Errors of Metabolism (IEM), pose significant diagnostic challenges. Case reports serve as key but computationally underutilized resources to inform diagnosis. Clinical dense information extraction refers to organizing medical information into structured predefined categories. Large Language Models (LLMs) may enable scalable information extraction from case reports but are rarely evaluated for this task. We introduce CaseReportBench, an expert-annotated dataset for dense information extraction of case reports, focusing on IEMs. Using this dataset, we assess various models and prompting strategies, introducing novel approaches such as category-specific prompting and subheading-filtered data integration. Zero-shot chain-of-thought prompting offers little advantage over standard zero-shot prompting. Category-specific prompting improves alignment with the benchmark. The open-source model Qwen2.5-7B outperforms GPT-4o for this task. Our clinician evaluations show that LLMs can extract clinically relevant details from case reports, supporting rare disease diagnosis and management. We also highlight areas for improvement, such as LLMs' limitations in recognizing negative findings important for differential diagnosis. This work advances LLM-driven clinical natural language processing and paves the way for scalable medical AI applications.

Speech patterns have been identified as potential diagnostic markers for neuropsychiatric conditions. However, most studies only compare a single clinical group to healthy controls, whereas clinical practice often requires differentiating between multiple potential diagnoses (multiclass settings). To address this, we assembled a dataset of repeated recordings from 420 participants (67 with major depressive disorder, 106 with schizophrenia and 46 with autism, as well as matched controls), and tested the performance of a range of conventional machine learning models and advanced Transformer models on both binary and multiclass classification, based on voice and text features. While binary models performed comparably to previous research (F1 scores between 0.54-0.75 for autism spectrum disorder, ASD; 0.67-0.92 for major depressive disorder, MDD; and 0.71-0.83 for schizophrenia); when differentiating between multiple diagnostic groups performance decreased markedly (F1 scores between 0.35-0.44 for ASD, 0.57-0.75 for MDD, 0.15-0.66 for schizophrenia, and 0.38-0.52 macro F1). Combining voice and text-based models yielded increased performance, suggesting that they capture complementary diagnostic information. Our results indicate that models trained on binary classification may learn to rely on markers of generic differences between clinical and non-clinical populations, or markers of clinical features that overlap across conditions, rather than identifying markers specific to individual conditions. We provide recommendations for future research in the field, suggesting increased focus on developing larger transdiagnostic datasets that include more fine-grained clinical features, and that can support the development of models that better capture the complexity of neuropsychiatric conditions and naturalistic diagnostic assessment.

Despite being widely used to support clinical care, general-purpose large multimodal models (LMMs) have generally shown poor or inconclusive performance in medical image interpretation, particularly in pathology, where gigapixel images are used. However, prior studies have used either low-resolution thumbnails or random patches, which likely underestimated model performance. Here, we ask whether LMMs can be adapted to reason coherently and accurately in the evaluation of such images. In this study, we introduce Gigapixel Image Agent for Navigating Tissue (GIANT), the first framework that allows LMMs to iteratively navigate whole-slide images (WSIs) like a pathologist. Accompanying GIANT, we release MultiPathQA, a new benchmark, which comprises 934 WSI-level questions, encompassing five clinically-relevant tasks ranging from cancer diagnosis to open-ended reasoning. MultiPathQA also includes 128 questions, authored by two professional pathologists, requiring direct slide interpretation. Using MultiPathQA, we show that our simple agentic system substantially outperforms conventional patch- and thumbnail-based baselines, approaching or surpassing the performance of specialized models trained on millions of images. For example, on pathologist-authored questions, GPT-5 with GIANT achieves 62.5% accuracy, outperforming specialist pathology models such as TITAN (43.8%) and SlideChat (37.5%). Our findings reveal the strengths and limitations of current foundation models and ground future development of LMMs for expert reasoning in pathology.