Vision-language models (VLMs) have gained significant attention in computational pathology due to their multimodal learning capabilities that enhance big-data analytics of giga-pixel whole slide image (WSI). However, their sensitivity to large-scale clinical data, task formulations, and prompt design remains an open question, particularly in terms of diagnostic accuracy. In this paper, we present a systematic investigation and analysis of three state of the art VLMs for histopathology, namely Quilt-Net, Quilt-LLAVA, and CONCH, on an in-house digestive pathology dataset comprising 3,507 WSIs, each in giga-pixel form, across distinct tissue types. Through a structured ablative study on cancer invasiveness and dysplasia status, we develop a comprehensive prompt engineering framework that systematically varies domain specificity, anatomical precision, instructional framing, and output constraints. Our findings demonstrate that prompt engineering significantly impacts model performance, with the CONCH model achieving the highest accuracy when provided with precise anatomical references. Additionally, we identify the critical importance of anatomical context in histopathological image an
We present ViDRiP-LLaVA, the first large multimodal model (LMM) in computational pathology that integrates three distinct image scenarios, including single patch images, automatically segmented pathology video clips, and manually segmented pathology videos. This integration closely mirrors the natural diagnostic process of pathologists. By generating detailed histological descriptions and culminating in a definitive sign-out diagnosis, ViDRiP-LLaVA bridges visual narratives with diagnostic reasoning. Central to our approach is the ViDRiP-Instruct dataset, comprising 4278 video and diagnosis-specific chain-of-thought instructional pairs sourced from educational histopathology videos on YouTube. Although high-quality data is critical for enhancing diagnostic reasoning, its creation is time-intensive and limited in volume. To overcome this challenge, we transfer knowledge from existing single-image instruction datasets to train on weakly annotated, keyframe-extracted clips, followed by fine-tuning on manually segmented videos. ViDRiP-LLaVA establishes a new benchmark in pathology video analysis and offers a promising foundation for future AI systems that support clinical decision-maki
Uterine diseases represent an important category of gynecologic pathology and require accurate histopathological assessment for diagnosis and treatment planning. Whole-slide images (WSI) have enabled the digital transformation of pathology workflows and provided new opportunities for artificial intelligence (AI) in computational pathology. In particular, multimodal models that jointly analyze histopathology images and pathology reports have shown promising potential for automated pathology report generation and AI-assisted diagnosis. However, the development of such systems remains limited by the scarcity of datasets that pair whole-slide images with clinically meaningful pathology reports. Instead, existing pathology datasets focus on patch- or slide-level annotations of a single endpoint (e.g., disease class), which do not fully capture the rich information in full clinical diagnostic workflow reports. Here, we introduce TUM-Uteria, a uterine pathology dataset comprising WSIs paired with diagnostic pathology reports at both the case and slide levels, collected from a tertiary medical center. The dataset contains 216 clinical cases, comprising 455 slide-level WSI-report pairs. The
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. Fo
Pathology is experiencing rapid digital transformation driven by whole-slide imaging and artificial intelligence (AI). While deep learning-based computational pathology has achieved notable success, traditional models primarily focus on image analysis without integrating natural language instruction or rich, text-based context. Current multimodal large language models (MLLMs) in computational pathology face limitations, including insufficient training data, inadequate support and evaluation for multi-image understanding, and a lack of autonomous, diagnostic reasoning capabilities. To address these limitations, we introduce PathChat+, a new MLLM specifically designed for human pathology, trained on over 1 million diverse, pathology-specific instruction samples and nearly 5.5 million question answer turns. Extensive evaluations across diverse pathology benchmarks demonstrated that PathChat+ substantially outperforms the prior PathChat copilot, as well as both state-of-the-art (SOTA) general-purpose and other pathology-specific models. Furthermore, we present SlideSeek, a reasoning-enabled multi-agent AI system leveraging PathChat+ to autonomously evaluate gigapixel whole-slide images
AI tools in pathology have improved screening throughput, standardized quantification, and revealed prognostic patterns that inform treatment. However, adoption remains limited because most systems still lack the human-readable reasoning needed to audit decisions and prevent errors. We present RECAP-PATH, an interpretable framework that establishes a self-learning paradigm, shifting off-the-shelf multimodal large language models from passive pattern recognition to evidence-linked diagnostic reasoning. At its core is a two-phase learning process that autonomously derives diagnostic criteria: diversification expands pathology-style explanations, while optimization refines them for accuracy. This self-learning approach requires only small labeled sets and no white-box access or weight updates to generate cancer diagnoses. Evaluated on breast and prostate datasets, RECAP-PATH produced rationales aligned with expert assessment and delivered substantial gains in diagnostic accuracy over baselines. By uniting visual understanding with reasoning, RECAP-PATH provides clinically trustworthy AI and demonstrates a generalizable path toward evidence-linked interpretation.
Pathology foundation models (PFMs), as large-scale pre-trained models tailored for computational pathology, have significantly advanced a wide range of applications. Their ability to leverage prior knowledge from massive datasets has streamlined the development of intelligent pathology models. However, we identify several critical and interrelated ethical risks that remain underexplored, yet must be addressed to enable the safe translation of PFMs from lab to clinic. These include the potential leakage of patient-sensitive attributes, disparities in model performance across demographic and institutional subgroups, and the reliance on diagnosis-irrelevant features that undermine clinical reliability. In this study, we pioneer the quantitative analysis for ethical risks in PFMs, including privacy leakage, clinical reliability, and group fairness. Specifically, we propose an evaluation framework that systematically measures key dimensions of ethical concern: the degree to which patient-sensitive attributes can be inferred from model representations, the extent of performance disparities across demographic and institutional subgroups, and the influence of diagnostically irrelevant feat
Autonomous computational pathology (ACP) converts high-level pathology analysis goals into executable, traceable and clinically bounded workflows. Realizing this capability requires adapting general agentic harness systems to pathology-specific tasks, tools, evidence standards and clinical claim boundaries. We contribute ACP-Bench, a framework that adapts existing harness systems from computational pathology support toward ACP workflow capability. ACP-Bench evaluates 41 pathology workflow tasks, including 24 biomarker, 7 morphology and 10 prognosis tasks spanning 6 body-system groups and 9 endpoint families. The benchmark evaluates 9 models and 3 harness groups (Claude Code, Codex and Open Code), yielding 369 complete trajectories. ACP-Bench evaluates each trajectory across workflow execution, diagnostic performance and clinical-boundary alignment, combining expert-adjudicated process audits, diagnostic assessment and pathologist-validated safety review. Across evaluated systems, workflow initiation, task interpretation and diagnostic reporting were more mature than tool-bound execution, result binding and reflective workflow revision, and formal end-to-end completion remained rare
Recent advances in computational pathology have led to the emergence of numerous foundation models. These models typically rely on general-purpose encoders with multi-instance learning for whole slide image (WSI) classification or apply multimodal approaches to generate reports directly from images. However, these models cannot emulate the diagnostic approach of pathologists, who systematically examine slides at low magnification to obtain an overview before progressively zooming in on suspicious regions to formulate comprehensive diagnoses. Instead, existing models directly output final diagnoses without revealing the underlying reasoning process. To address this gap, we introduce CPathAgent, an innovative agent-based approach that mimics pathologists' diagnostic workflow by autonomously navigating across WSI based on observed visual features, thereby generating substantially more transparent and interpretable diagnostic summaries. To achieve this, we develop a multi-stage training strategy that unifies patch-level, region-level, and WSI-level capabilities within a single model, which is essential for replicating how pathologists understand and reason across diverse image scales.
Background: Artificial intelligence (AI) is improving the efficiency and accuracy of cancer diagnostics. The performance of pathology AI systems has been almost exclusively evaluated on European and US cohorts from large centers. For global AI adoption in pathology, validation studies on currently under-represented populations - where the potential gains from AI support may also be greatest - are needed. We present the first study with an external validation cohort from the Middle East, focusing on AI-based diagnosis and Gleason grading of prostate cancer. Methods: We collected and digitised 339 prostate biopsy specimens from the Kurdistan region, Iraq, representing a consecutive series of 185 patients spanning the period 2013-2024. We evaluated a task-specific end-to-end AI model and two foundation models in terms of their concordance with pathologists and consistency across samples digitised on three scanner models (Hamamatsu, Leica, and Grundium). Findings: Grading concordance between AI and pathologists was similar to pathologist-pathologist concordance with Cohen's quadratically weighted kappa 0.801 vs. 0.799 (p=0.9824). Cross-scanner concordance was high (quadratically weight
Pathology images are crucial for diagnosing and managing various diseases by visualizing cellular and tissue-level abnormalities. Recent advancements in artificial intelligence (AI), particularly multimodal models like ChatGPT, have shown promise in transforming medical image analysis through capabilities such as medical vision-language question answering. However, there remains a significant gap in integrating pathology image data with these AI models for clinical applications. This study benchmarks the performance of GPT on pathology images, assessing their diagnostic accuracy and efficiency in real-word clinical records. We observe significant deficits of GPT in bone diseases and a fair-level performance in diseases from other three systems. Despite offering satisfactory abnormality annotations, GPT exhibits consistent disadvantage in terminology accuracy and multimodal integration. Specifically, we demonstrate GPT's failures in interpreting immunohistochemistry results and diagnosing metastatic cancers. This study highlight the weakness of current generalist GPT model and contribute to the integration of pathology and advanced AI.
Tissue detection is a crucial first step in most digital pathology applications. Details of the segmentation algorithm are rarely reported, and there is a lack of studies investigating the downstream effects of a poor segmentation algorithm. Disregarding tissue detection quality could create a bottleneck for downstream performance and jeopardize patient safety if diagnostically relevant parts of the specimen are excluded from analysis in clinical applications. This study aims to determine whether performance of downstream tasks is sensitive to the tissue detection method, and to compare performance of classical and AI-based tissue detection. To this end, we trained an AI model for Gleason grading of prostate cancer in whole slide images (WSIs) using two different tissue detection algorithms: thresholding (classical) and UNet++ (AI). A total of 33,823 WSIs scanned on five digital pathology scanners were used to train the tissue detection AI model. The downstream Gleason grading algorithm was trained and tested using 70,524 WSIs from 13 clinical sites scanned on 13 different scanners. There was a decrease from 116 (0.43%) to 22 (0.08%) fully undetected tissue samples when switching f
Computational pathology demands both visual pattern recognition and dynamic integration of structured domain knowledge, including taxonomy, grading criteria, and clinical evidence. In practice, diagnostic reasoning requires linking morphological evidence with formal diagnostic and grading criteria. Although multimodal large language models (MLLMs) demonstrate strong vision language reasoning capabilities, they lack explicit mechanisms for structured knowledge integration and interpretable memory control. As a result, existing models struggle to consistently incorporate pathology-specific diagnostic standards during reasoning. Inspired by the hierarchical memory process of human pathologists, we propose PathMem, a memory-centric multimodal framework for pathology MLLMs. PathMem organizes structured pathology knowledge as a long-term memory (LTM) and introduces a Memory Transformer that models the dynamic transition from LTM to working memory (WM) through multimodal memory activation and context-aware knowledge grounding, enabling context-aware memory refinement for downstream reasoning. PathMem achieves SOTA performance across benchmarks, improving WSI-Bench report generation (12.8%
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 dat
Accurate diagnosis of disease often depends on the exhaustive examination of Whole Slide Images (WSI) at microscopic resolution. Efficient handling of these data-intensive images requires lossy compression techniques. This paper investigates the limitations of the widely-used JPEG algorithm, the current clinical standard, and reveals severe image artifacts impacting diagnostic fidelity. To overcome these challenges, we introduce a novel deep-learning (DL)-based compression method tailored for pathology images. By enforcing feature similarity of deep features between the original and compressed images, our approach achieves superior Peak Signal-to-Noise Ratio (PSNR), Multi-Scale Structural Similarity Index (MS-SSIM), and Learned Perceptual Image Patch Similarity (LPIPS) scores compared to JPEG-XL, Webp, and other DL compression methods.
Ensuring diagnostic performance of AI models before clinical use is key to the safe and successful adoption of these technologies. Studies reporting AI applied to digital pathology images for diagnostic purposes have rapidly increased in number in recent years. The aim of this work is to provide an overview of the diagnostic accuracy of AI in digital pathology images from all areas of pathology. This systematic review and meta-analysis included diagnostic accuracy studies using any type of artificial intelligence applied to whole slide images (WSIs) in any disease type. The reference standard was diagnosis through histopathological assessment and / or immunohistochemistry. Searches were conducted in PubMed, EMBASE and CENTRAL in June 2022. We identified 2976 studies, of which 100 were included in the review and 48 in the full meta-analysis. Risk of bias and concerns of applicability were assessed using the QUADAS-2 tool. Data extraction was conducted by two investigators and meta-analysis was performed using a bivariate random effects model. 100 studies were identified for inclusion, equating to over 152,000 whole slide images (WSIs) and representing many disease types. Of these, 4
In this paper, we introduce a clinical diagnosis template-based pipeline to systematically collect and structure pathological information. In collaboration with pathologists and guided by the the College of American Pathologists (CAP) Cancer Protocols, we design a Clinical Pathology Report Template (CPRT) that ensures comprehensive and standardized extraction of diagnostic elements from pathology reports. We validate the effectiveness of our pipeline on TCGA-BRCA. First, we extract pathological features from reports using CPRT. These features are then used to build CTIS-Align, a dataset of 80k slide-description pairs from 804 WSIs for vision-language alignment training, and CTIS-Bench, a rigorously curated VQA benchmark comprising 977 WSIs and 14,879 question-answer pairs. CTIS-Bench emphasizes clinically grounded, closed-ended questions (e.g., tumor grade, receptor status) that reflect real diagnostic workflows, minimize non-visual reasoning, and require genuine slide understanding. We further propose CTIS-QA, a Slide-level Question Answering model, featuring a dual-stream architecture that mimics pathologists' diagnostic approach. One stream captures global slide-level context vi
Anomaly detection in computational pathology aims to identify rare and scarce anomalies where disease-related data are often limited or missing. Existing anomaly detection methods, primarily designed for industrial settings, face limitations in pathology due to computational constraints, diverse tissue structures, and lack of interpretability. To address these challenges, we propose Ano-NAViLa, a Normal and Abnormal pathology knowledge-augmented Vision-Language model for Anomaly detection in pathology images. Ano-NAViLa is built on a pre-trained vision-language model with a lightweight trainable MLP. By incorporating both normal and abnormal pathology knowledge, Ano-NAViLa enhances accuracy and robustness to variability in pathology images and provides interpretability through image-text associations. Evaluated on two lymph node datasets from different organs, Ano-NAViLa achieves the state-of-the-art performance in anomaly detection and localization, outperforming competing models.
Intraoperative pathology is pivotal to precision surgery, yet its clinical impact is constrained by diagnostic complexity and the limited availability of high-quality frozen-section data. While computational pathology has made significant strides, the lack of large-scale, prospective validation has impeded its routine adoption in surgical workflows. Here, we introduce CRISP, a clinical-grade foundation model developed on over 100,000 frozen sections from eight medical centers, specifically designed to provide Clinical-grade Robust Intraoperative Support for Pathology (CRISP). CRISP was comprehensively evaluated on more than 15,000 intraoperative slides across nearly 100 retrospective diagnostic tasks, including benign-malignant discrimination, key intraoperative decision-making, and pan-cancer detection, etc. The model demonstrated robust generalization across diverse institutions, tumor types, and anatomical sites-including previously unseen sites and rare cancers. In a prospective cohort of over 2,000 patients, CRISP sustained high diagnostic accuracy under real-world conditions, directly informing surgical decisions in 92.6% of cases. Human-AI collaboration further reduced diagn
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 matc