Whole-Slide Image Analysis

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17 papers in the last four weeks, up 89% on the four weeks before. 0.2% of all new papers.

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Latest papers 133

Oct 7, 2026cs.CV

Masked Feature Encoding for Large-Scale Whole Slide Image Representation

Whole slide image (WSI) analysis in computational pathology follows a multiple instance learning (MIL) pipeline where patch embeddings are extracted independently and aggregated for slide-level prediction, but within-slide variance from staining, scanner, and local texture can overwhelm the discriminative signal. We propose Masked Feature Encoding for Multiple Instance Learning (MFE-MIL), a feature-space masking framework that trains a lightweight MLP adapter jointly with a window-based masked reconstruction branch and a MIL classification head. The two objectives are complementary. Classification guides the adapter to suppress within-slide patch variance, while window-based masked reconstruction provides an auxiliary regularizer for the adapted features without using patch coordinates, coordinate graphs, or segmentation preprocessing. The raster patch-extraction order is used only as a weak implicit prior. At inference, the decoder is removed, leaving only the adapter and MIL head. Across CAMELYON16/17, PANDA, and TCGA-BRCA with four diverse encoders, MFE-MIL improves ACC/F1 for nearly all tested aggregator-encoder settings and AUC in most, outperforms coordinate-based spatial methods (CAMIL), and achieves higher AUC than 2DMamba on three of four datasets (UNI). On five TCGA survival cohorts it improves the average concordance index for every aggregator tested, its most consistent gain. Code is available at https://github.com/AtlasAnalyticsLab/MFE-MIL.

Haoyu He, Basile Tessier-Cloutier, Yang Wang +1

Department of Computer Science and Software Engineering (CSSE), Concordia University, Montreal, Canada · McGill University, Montreal, Canada · Mila – Quebec AI Institute, Montreal, Canada

Whole-Slide Image Analysis Medical Image Representation Learning Histopathology Image Classification Multiple Instance Learning Masked Image Modeling

Oct 6, 2026cs.CV

Multimodal Knowledge Distillation for Gastric Adenocarcinoma Classification from Whole-Slide Images

Gastric adenocarcinoma (GA) is a leading cause of cancer-related mortality worldwide, and accurate histopathological subtype classification from whole-slide images (WSIs) is essential for effective treatment planning. While multimodal approaches that integrate pathology report text with WSIs can improve classification, existing methods often depend on computationally expensive transformer architectures and large language models. We propose a multimodal knowledge distillation (MKD) framework that combines a pretrained WSI image encoder and a clinical text encoder using Low-Rank Multimodal Fusion (LMF) to efficiently model cross-modal interactions during training. Each WSI is represented as a bag of patches paired with a slide-level diagnostic caption. The teacher model learns fused image-text representations for subtype classification, while the student model distills this knowledge to enable accurate image-only inference. We evaluate our method on the PatchGastric benchmark dataset and achieve at least 3.35% higher mean accuracy than state-of-the-art approaches, without relying on transformer-based fusion, multi-task learning, or large language models. The source code is available at https://github.com/helomelo1/MKD-LMF.

Shrihari Dumbre, Bikash Santra

Indian Institute of Technology, Jodhpur

Cross-Modal Knowledge Distillation Multimodal Classification Histopathology Image Classification Whole-Slide Image Analysis

Oct 6, 2026cs.CV

CHARTER: Auditing Reference Substitution in Hierarchical Compact-Evidence Evaluation for Computational Pathology

In digital pathology, compact evidence is often used to explain or audit predictions made by whole-slide image multiple instance learning models. In hierarchical compact-evidence pipelines, candidate filtering introduces a strategy-specific candidate-conditioned prediction alongside the original full-bag prediction. If the evaluation reference changes while the intended target remains the original full-bag prediction, however, not only can the measured fidelity of the same compact evidence change, but comparisons between competing candidate strategies can also change. To make this dependence explicit, we introduce CHARTER, a reference-aware evaluation charter that asks researchers to DECLARE the intended target and reference, QUANTIFY candidate-induced prediction shift, and AUDIT the stability of comparative conclusions. Across the 15 comparisons in our main five-seed Random-K audit, 4 showed determinate reversals; in a matched native-ranking stress test, the ACMIL comparison changed from REVERSED to PRESERVED. CHARTER turns otherwise implicit candidate-filtering and reference choices into an auditable evaluation specification, helping distinguish genuine preservation of the intended prediction from apparent gains induced by changing the prediction being explained.

Hyun Do Jung, Jungwon Choi, Soojung Choi +2

Yonsei University · KAIST · Hallym University Chuncheon Sacred Heart Hospital

Computational Pathology Algorithmic Auditing Whole-Slide Image Analysis Explanation Evaluation

Oct 6, 2026cs.CV

Anchor-driven Multi-modal Multi-scale Expert Selection for Survival Prediction

The integrative analysis of histopathological Whole-Slide Images (WSIs) and transcriptomic profiles holds significant promise for cancer survival prediction. However, existing methods typically project multi-modal features directly into a shared latent space without explicit alignment, leading to the entanglement of mismatched morphological cues and molecular signals. Furthermore, current fusion strategies often treat the extreme spatial heterogeneity of WSIs uniformly, lacking mechanisms to adaptively prioritize clinically relevant tissue scales for individual patients. To address these limitations, we propose an Anchor-driven Multi-modal Multi-scale Expert Selection (AM

^2

ES) framework for survival prediction. Specifically, we present an Anchor-driven Multi-modal Fusion (AMF) module, which introduces learnable semantic anchors as cross-modal mediators to bridge the semantic gap by enforcing a structurally regularized alignment between transcriptomic features and multi-scale pathology representations. Built upon this aligned semantic space, we further design a Hierarchical Mixture-of-Experts (H-MoE) selection module to decouple the hierarchical prognostic selection process. Mimicking the pathologist's diagnostic workflow, H-MoE performs (i) Intra-scale Expert Filtering to discriminatively identify salient tumor regions within each magnification, and (ii) Inter-scale Hierarchy Routing to dynamically weight and select the most informative resolution levels. Extensive experiments on multiple TCGA cancer cohorts demonstrate that our AM

^2

ES achieves state-of-the-art performance while offering fine-grained interpretability by visualizing how specific molecular pathways drive the expert routing decisions across tissue scales. The code will be released at https://github.com/taozh2017/AM2ES.

Tao Zhou, Ying Hu, Huazhu Fu +3

School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China · Institute of Advanced Intelligence and Computing (IAIC), Agency for Science, Technology and Research (A*STAR), Singapore 138632 · School of Computer Science and Engineering, Southeast University, Nanjing 211189, China +2

Cancer Survival Prediction Mixture of Experts Multi-Scale Feature Fusion Multimodal Survival Analysis Multimodal Fusion Whole-Slide Image Analysis

Oct 4, 2026cs.LG

Cross-Modal Contrastive Learning for the Retrieval of Immunotherapy-Associated Molecular Signatures from Histopathology

Gastric Adenocarcinoma is a leading cause of cancer mortality. Although "Inflamed/Non-Inflamed" subtypes have been proposed to predict immunotherapy response, their identification relies on a costly 10-gene RNA signature. We propose a Cross-modal Contrastive Multiple Instance Learning (CCMIL) framework for cross-modal retrieval, imputing these molecular signatures directly from standard Hematoxylin & Eosin (H&E) slides. By leveraging a supervised contrastive objective, CCMIL aligns visual morphological patterns with molecular phenotypes into a shared latent space. This establishes an interpretable search-by-case retrieval engine, enabling pathologists to query a whole slide image to surface transcriptomically coherent neighbors and approximate RNA signatures without genomic sequencing at inference. Our results demonstrate that this retrieval-first approach captures the continuous phenotypic spectrum of tumor inflammation and yields clinically interpretable attention heatmaps. Furthermore, the learned representation also supports competitive downstream classification, providing a practical molecular pre-screening strategy.

Sigrid Vila-Bagaria, Mar Teixidó, Miquel Piñol +3

Signal Theory and Communications Department (TSC) Universitat Politècnica de Catalunya - BarcelonaTech (UPC) · Cancer Biomarkers Research Group (GReBiC) - IRB Lleida

Computational Pathology Cross-Modal Retrieval Multimodal Contrastive Learning Multiple Instance Learning Gene Expression Prediction from Histopathology Images Whole-Slide Image Analysis

Oct 1, 2026cs.AI

AI-assisted mitotic counting improves reproducibility and efficiency across multiple tumour types

Mitotic counting is an important component of tumour grading, diagnosis and prognostic assessment across several tumour types, but manual assessment is time-consuming and subject to inter-pathologist variability. To help address these challenges, we developed MitPro, an AI tool designed to improve consistency and efficiency by directing pathologists towards regions with the highest predicted mitotic activity and highlighting mitotic figures for review, while retaining pathologist control over region selection and the final count. We evaluated its effect on the reproducibility and efficiency of mitotic counting in a retrospective, non-interventional, paired reader study comprising 385 whole-slide images from 3 centres in 3 countries and 7 tumour types using 3 different scanners. 13 pathologists participated, with each slide assessed independently by 3 pathologists without AI assistance and again with AI assistance after a minimum 2 week washout period. Across all slides, AI-assisted counting increased the intraclass correlation coefficient from 0.589 to 0.949. Mean pathologist-level median assessment time decreased from 286.4 to 127.8 seconds, corresponding to an average saving of 151.8 seconds per assessment. Improvements in agreement and efficiency were also observed in supporting analyses using HALO AP and Sectra image management systems and in 2 additional tumour types outside the main study population. AI-assisted assessment was associated with a subtle shift towards higher mitotic counts and scores, consistent with identification of more active mitotic hotspots and fewer missed mitotic figures. The frequency of score change between unassisted and AI-assisted assessment was comparable with inter-pathologist variation during routine counting. These findings support the use of MitPro as an assistive tool for more consistent and efficient mitotic assessment in routine practice.

Simon Graham, Mostafa Jahanifar, Quoc Dang Vu +15

Histofy Ltd, Coventry, United Kingdom · Vilnius University Faculty of Medicine and National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania · Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom +5

Computational Pathology Human-AI Collaboration Whole-Slide Image Analysis

Sep 30, 2026eess.IV

Nonparametric Distribution Matching for Self-Supervised Whole-Slide Image Condensation

Histological whole-slide images (WSIs) are central to computational pathology but pose severe computational challenges due to their extremely high resolution, often spanning several gigabytes per slide. To enable scalable learning, existing methods apply self-supervised data condensation to reduce computational cost, but typically rely on heuristic prototype learning and do not explicitly preserve learning-relevant feature distributions for downstream tasks. In response, we introduce a principled reformulation of WSI condensation as a distribution-matching problem under a fixed representational lens, and develop NICER, a tractable approximation framework based on a nonparametric prior with slide-adaptive capacity. Experiments on five histopathology datasets, together with clinical evaluation from a board-certified pathologist, show that NICER consistently outperforms prior methods, achieving an average accuracy improvement of 7.44% while offering improved efficiency-accuracy trade-offs, highlighting the benefits of principled, distribution-aware condensation for scalable histological representation learning. Source codes are available in https://github.com/nmduonggg/NICER.

Duong M. Nguyen, Trong Nghia Hoang, Hang Thi Nguyen +3

University of Illinois Urbana-Champaign · Washington State University · Hanoi Medical University +2

Computational Pathology Distribution Matching Dataset Distillation Dataset Condensation Whole-Slide Image Analysis

Sep 30, 2026eess.IV

The Effect of Tissue Detection on False Positives of Diffusion-Based Artifact Detection in Histopathology

One-class artifact detectors for whole-slide images learn normal tissue from a clean training pool and flag departures from it. The pool is built by a preprocessing pipeline whose tissue-detection step is usually treated as neutral. We tested whether it is. On 16 annotated slides from The Cancer Genome Atlas, we rebuilt the clean pool of a diffusion-based detector with different tissue detection methods and compared the resulting models in a four-fold cross-validation. Per-slide saturation-Otsu detection excluded normal tissue, chiefly tissue with large clear spaces such as adipose tissue and alveolar parenchyma, and on slides with thick marker ink kept the ink while excluding ordinary tissue. Replacing it with entropy-based detection reduced the false-positive fraction on held-out clean slides from 0.102 to 0.016, in every fold and with a second training seed, without loss of sensitivity; the gain came from the composition of the pool, not its size. Across three tissue detection methods, false positives followed the fraction of such clear-space tissue in the pool, a statistic that needs no labels or training (0.103, 0.016 and 0.009). The effect did not carry over at the same size to a nearest-neighbour detector on foundation-model features. On an external cohort, the curated pool lowered clean-control false positives by about 20%, far less than on the development slides, and the remaining cross-center loss was not explained by stain differences. For one-class quality control, tissue detection decides what the model learns as normal and should be chosen and reported accordingly.

Konstantinos Moutselos, Ilias Maglogiannis

Department of Digital Systems, University of Piraeus, Piraeus, Greece

Computational Pathology Diffusion-Based OOD Detection Whole-Slide Image Analysis

Sep 30, 2026cs.AI

GATE-ST: Gene-Aware Text-image Encoder for Spatial Transcriptomics

Spatial transcriptomics enables spatially resolved gene expression analysis from slide-level images while preserving morphological features, providing valuable information for studying disease mechanisms and developing treatments. However, spatial gene expression profiling typically requires expensive and time-consuming tests. While existing image-based prediction optimizations mostly revolve around including positional embeddings and further image-based changes, text-based optimizations remain relatively unexplored. We present GATE-ST, which incorporates text-based inputs into image-based spatial gene expression predictions. With this approach, generated text descriptions of genes are utilized to better spatial transcriptomics prediction results. Gene summaries are put through a text encoder, generating embeddings that integrate with image embeddings through cross-attention layers to align with morphological features. We demonstrate the effectiveness of such text inputs by benchmarking performance against random gene embeddings and multiple other image-text fusion architectures, and show that GATE-ST outperforms these alternatives. Our results demonstrate the effectiveness of GATE-ST in pathology imaging, which may greatly reduce the time and cost of accurate spatial transcriptomic predictions, proving the potential of text-guided spatial gene expression prediction.

Lucas Ni, Jian Luo, Wentao Huang +1

Ridge High School Basking Ridge, United States · Stony Brook University Stony Brook, United States

Spatial Transcriptomics Multimodal Embedding Spatial Gene Expression Prediction Gene Expression Prediction from Histopathology Images Whole-Slide Image Analysis

Sep 29, 2026cs.CV

Towards Scalable Context-Aware Single-Cell Spatial Transcriptomics Prediction from Histology Images

Predicting gene expression from H&E-stained histology images offers a scalable alternative to costly spatial transcriptomics, yet most existing methods operate at the spot level, where signals from multiple cells are aggregated and critical cellular heterogeneity is obscured. Extending this paradigm to single-cell resolution is non-trivial. Naively applying pathology foundation models faces a scale mismatch: their patch-level representations mix multiple cells, whereas per-cell cropping or resizing distorts morphology and removes local context. Conversely, segmentation-based models without strong pretrained visual encoders often lack the morphological representation capacity needed for accurate molecular prediction and inherit errors from imperfect cell boundary masks. Here, we present CELLO, an efficient end-to-end framework that performs a single pathology foundation model forward pass per image and uses grid sampling to extract location-specific features for all cells simultaneously. We further introduce a distance-decay cross-attention module that refines each cell representation using spatially biased local morphological context. Using 52 public Xenium-H&E pairs from HEST-1k that span 12 organs and approximately 10 million cells, CELLO improves the average predictive accuracy over the evaluated baselines while reducing the mean whole-slide inference time compared to DeepSpot2Cell, a 14.0x speed-up on average that excludes upstream cell segmentation. Our work establishes a scalable foundation for single-cell gene expression prediction from H&E images.

Zijun Gao, Chunbin Gu, Jinxi Xiang +2

The Chinese University of Hong Kong · Stanford University School of Medicine

Spatial Transcriptomics Spatial Gene Expression Prediction Gene Expression Prediction from Histopathology Images Whole-Slide Image Analysis

Sep 29, 2026cs.CV

What Makes High-Magnification Knowledge Transferable? A Study of Cross-Resolution Distillation in Whole-Slide Imaging

Cross-resolution knowledge distillation aims to improve low-magnification whole- slide analysis by transferring high-magnification representations, yet the conditions for useful transfer remain unclear. We develop a decomposition-based analysis of teacher access, representation loss, and model excess, motivating three questions: whether (a) teacher targets help the task, (b) low-magnification students can predict them, and (c) slide models benefit from those predictions. We investigate them through controlled experiments across ten pathology cohorts spanning classifi- cation, grading, and survival prediction. In the main comparison, providing teacher regional means alongside native low-magnification features improves downstream performance in all ten cohorts. Direct prediction achieves lower reconstruction error than residual prediction, yet the predicted features underrepresent variation in the teacher targets. Moreover, better reconstruction does not consistently improve downstream scores, and retaining native features changes performance even when the predicted teacher features are held fixed. Together, these findings expose a gap between reconstructing teacher representations and realizing their downstream value. They challenge the sufficiency of reconstruction error as a measure of cross-resolution transfer and provide a diagnostic framework for examining where that transfer breaks down. Future distillation designs must account for both what students can predict and how slide models use those predictions.

Zhiyuan Yang, Jiahao Cheng, Mahdi S. Hosseini

Department of Computer Science and Software Engineering (CSSE) Concordia University Montreal, Canada · Department of Computer Science and Software Engineering (CSSE) Concordia University Montreal, Canada Mila – Quebec AI Institute Montreal, Canada

Feature-Based Knowledge Distillation Knowledge Distillation Whole-Slide Image Analysis

Sep 28, 2026cs.CV

HERO: Histology Encoder for Robust Representation in Oncology

Foundation models trained on large pathology image corpora now provide strong, transferable representations for computational pathology. Over the past few years a series of such models has been released, each trained on more slides than the last; on standard classification and segmentation benchmarks, the leading models are now separated by small margins. In clinical use, however, the foundation model is applied to images from hospitals, scanners, and staining protocols outside its training data. Encoders generally embed these acquisition factors alongside biological information, which may introduce downstream errors and hinder safe clinical adoption. A pathology foundation model should therefore be robust to acquisition shift without giving up representation quality, yet robustness is seldom the axis along which models are compared. In this report, we introduce HERO (Histology Encoder for Robust Representation in Oncology), a ViT-G/14 pathology foundation model trained with the DINO and iBOT objectives and refined with high-resolution Gram anchoring on a morphology-balanced corpus of 500 million tiles from approximately 575,000 clinical whole-slide images. Across the evaluated public benchmarks, HERO shows the strongest robustness to center, scanner, and stain variation among the compared state-of-the-art foundation models, performs comparably on tile-level classification, segmentation, and gene-expression prediction, ranks first on average across 39 evaluated slide-level clinical tasks, and, under an equal-weighted framework-level analysis, has the best average rank across the six benchmark frameworks.

Zhi Li, Eghbal Amidi, Yating Cheng +12

Caris Life Sciences, Irving, TX, United States

Computational Pathology Domain Generalization Pathology Foundation Models Medical Image Representation Learning Whole-Slide Image Analysis

Sep 28, 2026cs.CV

Role-Guided MOE for Encoder-Level Pathology Representation Learning in WSI Classification

Whole slide image classification is a fundamental task in computational pathology, where patch representation quality directly affects downstream aggregation and slide-level discriminability. Pathology foundation models are widely adopted as frozen feature extractors for WSI classification; however, their fixed encoders may produce representations insufficiently adapted to target-specific tissue patterns and discriminative cues. Fine-tuning can improve target adaptation, but introduces a trade-off between pathology-specific representation capacity and adaptation efficiency, particularly in data-scarce settings. To address this, we propose a pathology role-guided mixture-of-experts feed-forward network (MoE-FFN) framework for efficient encoder-level representation learning. We design a two-stage training paradigm to establish and adapt pathology-aware expert specialization. In source-domain expert initialization, pathology-specific priors are distilled from a frozen Virchow2 teacher into a lightweight DINOv2-small student, while role prototypes serve as weak pathological anchors to encourage distinct expert functions. MoE-FFN blocks are introduced into selected high-level transformer layers to provide transformation diversity for heterogeneous pathological patterns. In target-domain adaptation, the initialized experts are refined through asymmetric prototype-guided optimization, enhancing task-relevant positive evidence and separating confusable hard negatives. The resulting encoder extracts offline patch representations that can be directly integrated with standard MIL aggregators. Experiments on the public BRACS dataset and a private PAROTID WSI dataset across five representative backbones demonstrate consistent improvements over the strongest baseline.

Xinyu Ma, Xing Yang, Hongtao Jin +4

Artificial Intelligence Research Institute, Shenzhen MSU-BIT University, Shenzhen 518172, China · Shenzhen People’s Hospital, Shenzhen 518020, China

Pathology Foundation Models Mixture-of-Experts Models Medical Image Representation Learning Whole-Slide Image Analysis

Sep 28, 2026cs.CV

Modeling Whole-Slide Images as Dynamic Tumor Microenvironment Fields

Due to the gigapixel-scale nature of whole-slide images (WSIs), weakly supervised WSI analysis is commonly formulated as a multiple instance learning (MIL) problem, where patch-level features are aggregated into slide-level representations. However, diagnostic and prognostic evidence often arises from spatially coherent tumor microenvironment regions and their interactions, rather than isolated patches alone. Existing patch-level or static region-based methods usually overlook how tissue regions should be adaptively formed and subsequently evolved through microenvironment interactions across heterogeneous boundaries. In this paper, we propose Concept-Guided Tumor Microenvironment Evolution (TMEvolve), a reaction-diffusion-inspired framework that models WSIs as latent tumor microenvironment fields over discrete patch graphs. TMEvolve instantiates this view as a learnable graph-discretized evolution process over patch neighborhoods. It first forms adaptive soft tissue regions as coherent microenvironment units, then performs pseudo-time evolution through two complementary local dynamics: intra-region diffusion, which stabilizes latent states within coherent tissue compartments, and concept-guided boundary flux, which propagates visual feature signals and language-derived concept signals across heterogeneous region interfaces. The evolved microenvironment regions are finally aggregated for slide-level prediction. We evaluate TMEvolve on six datasets across three weakly supervised WSI tasks: survival prediction, gene expression prediction, and histological subtype classification. TMEvolve consistently improves over representative MIL methods, pathology foundation models, and concept-guided baselines. Ablation studies and visualizations further support the effectiveness and interpretability of TMEvolve, highlighting the value of dynamic region modeling and boundary interaction.

Lei Wu, Jiashuai Liu, Di Zhang +9

School of Computer Science and Technology, Xi’an Jiaotong University · University of Cambridge · Institute of Intelligent Medicine, Chinese Academy of Medical Sciences

Cancer Survival Prediction Histopathology Image Classification Multiple Instance Learning Whole-Slide Image Analysis

Sep 28, 2026cs.AI

MoSPR: Histology-to-Gene Expression Prediction with Morpho-Spatial Macrostates and Low-Rank Molecular Programs

Predicting molecular profiles from histopathology remains challenging because whole-slide images contain spatially organized, heterogeneous tissue patterns, while gene expression comprises thousands of correlated targets. We introduce MoSPR (Morpho-Spatial Program Regression), a linear framework that couples an adjacency-informed histology representation with a low-rank molecular basis. MoSPR clusters frozen patch embeddings into morphology microstates, aggregates their spatial adjacencies across the training cohort, and groups microstates with similar adjacency patterns into shared macrostates. Each slide is then represented by global morphology and macrostate-specific deviations, which are linearly mapped to coefficients of a training-derived low-rank gene-expression basis. Across three cancer cohorts from The Cancer Genome Atlas, MoSPR achieves the highest mean gene-expression prediction scores among all evaluated methods. Without pathway-level supervision, pathway scores derived from its predicted expression profiles rank first in eight of nine comparisons across three pathway collections. Ablation studies on the breast cancer cohort show complementary gains from adjacency-derived macrostate representation and low-rank molecular prediction. Moreover, with half of the training data on this cohort, MoSPR exceeds the full-data gene-prediction score of the strongest competing baseline. Finally, its linear formulation enables exact decomposition of each predicted expression profile into global and macrostate-specific molecular contributions, providing an interpretable link between spatially coherent macrostate regions and their associated molecular programs. Our code is available at https://github.com/Radisen-Panthera/MoSPR.

Dongmyung Shin, Geongyu Lee, Yesung Cho +1

OmixAI Co. Ltd. · Oncocross Co. Ltd. · Kyunghee University

Computational Pathology Explainable Medical Image Analysis Gene Expression Prediction from Histopathology Images Whole-Slide Image Analysis

Sep 24, 2026cs.CV

A Multimodal Dataset for Survival Prediction in Resected Pancreatic Ductal Adenocarcinoma

Survival research in pancreatic ductal adenocarcinoma (PDAC) is limited by the scarcity of datasets linking whole-slide histology with clinical, molecular, and long-term outcome data. We present a retrospective single-centre cohort of 302 patients who underwent PDAC resection at University Medical Center Gottingen. The dataset comprises 446 H&E whole-slide images, clinicopathological variables, targeted sequencing data for 154 patients, and overall-survival outcomes. During follow-up, 253 patients died, and the median follow-up was 76 months. To establish initial reference values, we evaluated fourteen survival-prediction configurations using identical five-repetition Monte Carlo cross-validation partitions. Ridge Cox regression using numeric clinicopathological variables achieved a mean concordance of

0.649 \pm 0.042

and

0.652 \pm 0.046

after adding KRAS and TP53 mutation status. The image-only attention model achieved

0.603 \pm 0.030

, while multimodal fusion achieved

0.619 \pm 0.025

, the highest concordance among the neural models. These results establish promising initial benchmarks for future research using this pancreas-specific multimodal dataset, paving the way for external validation.

Anh-Tien Nguyen, Mawuko Tettey, Jacqueline Michelle Metsch +14

Institute for Predictive Deep Learning for Medicine and Healthcare, Giessen University, Germany · Department of Medical Informatics, University Medical Center Göttingen, Germany · Institute of Pathology, University Medical Center Göttingen, Germany +2

Cancer Survival Prediction Oncology Multimodal Survival Analysis Whole-Slide Image Analysis Multimodal Learning

Sep 23, 2026cs.CV

Do Center Biases Propagate? Robustness of Pathology Foundation Models in Whole-Slide Image Classification

Pathology foundation models (PFMs) have transformed computational pathology through powerful representation learning from histopathological images. PFMs provide rich, discriminative representations for whole slide image (WSI) analysis, enabling tasks such as slide-level classification under multiple instance learning (MIL). However, these representations may also encode non-biological signals associated with acquisition centers, potentially introducing spurious shortcuts into downstream predictions. In this work, we evaluate center-associated robustness in WSI classification using a controlled training setting with increasing class-center correlations quantified by Cramér's V. We benchmark six PFMs across four datasets and two MIL aggregators, while evaluating ComBat as a robustification strategy. We further introduce the Area Under the Cramér's V Curve (AUCC) to jointly capture absolute classification performance and its degradation as spurious correlation increases. Results show that center-related information encoded by PFMs propagates to WSI-level predictions, with robustness depending on both the PFM representation and MIL aggregation strategy. Additionally, ComBat harmonization does not provide consistent robustness gains across datasets.

Ilán Carretero, Pablo Meseguer, Rocío del Amor +1

CVBLab, HumanTech, Universitat Politècnica de València (UPV), Valencia, Spain · Artikode Intelligence S.L., Valencia, Spain

Pathology Foundation Models Spurious Correlation Robustness Histopathology Image Classification Whole-Slide Image Analysis

Sep 21, 2026cs.CV

SLICEChat: Progressive In-Encoder Token Pruning for Whole-Slide Pathology Language Models

Whole-slide pathology images (WSIs) contain gigapixel-scale visual content, creating a major scalability challenge for slide-level multimodal large language models (MLLMs). Existing approaches process thousands of patch tokens and typically apply compression only after slide encoding, leaving multimodal attention computationally expensive. We introduce SLICEChat, a slide-level MLLM that integrates progressive token pruning within a hybrid Mamba--Transformer slide encoder. Mamba layers enable efficient long-range propagation, while Transformer layers preserve global interactions as the sequence is progressively shortened. Between stages, language-supervised, region-aware pruning removes spatially coherent low-utility regions under a controlled keep-rate schedule, producing compact slide representations before multimodal fusion. On SlideBench VQA, SLICEChat achieves 79.84% accuracy on TCGA and 59.09% on BCNB cohorts, outperforming prior slide-level pathology MLLMs, and achieves the highest overall WSI-Bench metrics. It also provides competitive memory usage and the inference latency among the evaluated models. These results demonstrate accurate and computationally efficient multimodal reasoning over gigapixel WSIs.

Ali Kerem Bozkurt, Baris Cem Bakay, Ibrahim Kulac +3

Kocı University, Department of Computer Engineering · Kocı University, Department of Pathology · Hacettepe University, Department of Artificial Intelligence and Data Engineering

Efficient Multimodal Inference Multimodal Large Language Models Multimodal Token Compression Visual Token Pruning Whole-Slide Image Analysis

Sep 21, 2026cs.CV

Patch-to-Global: Random Patch Diffusion for Globally Consistent Megapixel Artifact Inpainting in Whole Slide Images

Although deep learning has advanced Whole Slide Image (WSI) Analysis, tissue artifacts like bubbles and folds often cause silent failures by concealing essential morphology. Current pathology image restoration methods are mostly restricted to small patches, struggling to maintain global structural coherence at a megapixel scale. We introduce RestorePath, a framework for globally consistent megapixel scale inpainting that reconstructs diagnostic structures in histological image to prevent incorrect high-confidence predictions and lower error rates. Our model utilizes a Latent Diffusion Model (LDM) conditioned on Pathology Foundation Model (PFM) embeddings, integrating Large Kernel Attention (LKA) to manage long-range dependencies during random patch diffusion. Enhanced by Distance-Weighted Interpolation (DWI) and an Adaptive Guidance Scale (AGS), RestorePath ensures structural consistency and fidelity by modulating information from surrounding patches. Evaluations across TCGA-BRCA, BACH, and Camelyon16 datasets for images ranging from 512 to 4608 pixels demonstrate state-of-the-art performance in maintaining histological consistency. RestorePath significantly improves downstream Computational Pathology (CP) tasks, outperforming both raw artifact images and the conventional Detect-and-Discard (D&D) approach. The code is available at https://github.com/PathfinderLab/RestorePath

Hyeseong Lee, Eunsu Kim, D M Bappy +6

Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea · Department of Pathology, Korea University Anam Hospital, College of Medicine, Korea University, Seoul, Korea · Seegene Medical Foundation, Seoul, Korea +3

Computational Pathology Diffusion Models for Image Restoration Image Inpainting Whole-Slide Image Analysis

Sep 14, 2026cs.CV

Hyperbolic Contrastive Learning with Entailment for Spatial Transcriptomics

Spatial Transcriptomics (ST) has transformed biomedical research by enabling the spatial mapping of gene expression across tissue sections. However, high operational costs, specialized equipment requirements, and sensitivity to experimental noise limit the accessibility and scalability of ST. Recent computer vision approaches aim to overcome these limitations by predicting spatial gene expression directly from histopathology images. While effective, current approaches often suffer from gene expression over-smoothing and overly uniform predictions across tissue regions, suggesting that further progress depends on learning representations that reflect the hierarchical and asymmetric structure of gene regulation and tissue morphology. To address these issues, we propose Hyperbolic Contrastive Learning with Entailment for Spatial Transcriptomics (HyCLoST), a hyperbolic contrastive learning model that captures the intrinsic hierarchical relationships within ST data. By leveraging hyperbolic geometry and a gene-to-image entailment loss, HyCLoST learns structured, biologically grounded representations that improve gene expression prediction accuracy, achieving a 6% reduction in MSE and an 8% increase in PCC across 26 ST datasets, over previous methods. Our source code is publicly available at https://github.com/BCV-Uniandes/HyCLoST

Daniela Vega, Paula Cárdenas, Hannah Ceballos +2

Center for Research and Formation in Artificial Intelligence Universidad de los Andes, Colombia

Contrastive Learning Spatial Transcriptomics Spatial Gene Expression Prediction Gene Expression Prediction from Histopathology Images Whole-Slide Image Analysis Hyperbolic Representation Learning

Sep 11, 2026eess.IV

Seamless Whole Slide Label-Free Virtual Staining

Label-free virtual staining offers a compelling, non-destructive alternative to standard histopathology; however, its clinical adoption is hindered by the computational bottlenecks inherent to processing gigapixel Whole Slide Images (WSIs). Current deep learning approaches require patch-based inference to avoid memory constraints, which disrupts global tissue continuity and introduces tiling artifacts--displaying visible seams and color shifts. To address this, we introduce the Consistency Memory Bank (COMB), a novel label-free virtual staining framework that enforces spatial and channel consistency across tiles without memory bottlenecks. COMB decouples context storage from computation, utilizing a dynamic retrieval mechanism to fetch feature representations from adjacent tiles. This enables a retrieval-based context integration strategy that adopts local padding to resolve spatial discontinuities and neighbor-aware channel attention to stabilize statistical drift. Further optimized with a sliding window schedule to ensure minimal memory overhead, our method demonstrates superior performance over state-of-the-art baselines, achieving significant improvements in both perceptual fidelity and tiling consistency, while suggesting its downstream utility in tumor segmentation. Code is available at https://github.com/dou0000/COMB.

Dou Hoon Kwark, Kianoush Falahkheirkhah, Ji-hun Oh +3

University of Illinois Urbana-Champaign, Urbana, IL, USA · National Center for Supercomputing Applications, Urbana, IL, USA

Computational Pathology Virtual Staining Whole-Slide Image Analysis

Sep 3, 2026cs.CV

Semantic-Aware Subgraph State Space Model for WSI Classification in Histopathology

Histopathological subtyping relies on the recognition of characteristic histological patterns. These patterns may be expressed by individual tissue structures or by the spatial distribution and co-occurrence of multiple structures, and they often span irregularly shaped tissue regions, termed semantic units in this work. However, conventional patch-based representations may fragment such units and fail to explicitly preserve their internal spatial organization, while efficiently modeling relationships among numerous spatially separated units remains challenging. To address these limitations, we propose the Semantic-Aware Subgraph State Space Model (SASG-SSM), a flexible and efficient framework for whole slide image (WSI) classification. Semantic-Aware Subgraphs (SASGs) first approximate irregularly shaped semantic units by adaptively grouping spatially connected patches guided by class-agnostic visual-semantic priors. By representing patches as graph nodes with adjacency edges, SASGs preserve their internal spatial organization rather than treating them as an unordered set. A Subgraph State Space Module (SG-SSM) subsequently combines a graph neural network encoder for intra-subgraph topology encoding with a Mamba-based state space encoder for efficient contextualization across large numbers of subgraphs. This module integrates local structural information within semantic units with global contextual information arising from their distribution and co-occurrence across the WSI, while efficiently modeling a large number of spatially distributed regions. Extensive experiments across four WSI subtyping datasets demonstrate consistent advantages over representative state-of-the-art methods. Further evaluations under small-cohort and few-shot settings demonstrate robustness and data efficiency under limited training data. Code will be released at https://github.com/HLSvois/SASG-SSM.

Feixing Chen, Hao Lu, Lin Luo +1

National College for Excellent Engineers Beihang University Beijing, P.R.C. 100191 · School of Biological Science and Medical Engineering Beihang University Beijing, P.R.C. 100191 · College of Engineering Peking University Beijing, P.R.C. 100871

Visual SSMs Histopathology Image Classification Whole-Slide Image Analysis

Sep 2, 2026cs.CV

Morphology signal in whole slide image foundation models can automatically triage slides

Patient exams in the cancer diagnosis and staging process typically generate several whole slide images (WSIs). One of the initial steps in training models on WSI data is identifying one or a few slides containing tumor or other diagnostic biomarkers necessary for downstream prediction tasks such as estimating recurrence risk or progression-free survival. This step requires tedious manual curation by experienced pathologists. Many published datasets make the artificial assumption of 1 slide per patient. Alternatively, all slides per patient may be used for model training, which may dilute the signal from the few slides containing tumor or other relevant information. In this paper, we present a pipeline to overcome these challenges using publicly available WSI foundation models (FMs). Our evaluations show that ranking WSIs based on predictions from zero-shot classification using WSI FMs accurately identifies slides with the most tumor, indicating that WSI FMs contain sufficient morphology signal to automatically triage slides. We also present a formulation for ranked evaluation to benchmark FM performance in slide triage. We show, on multiple datasets, that tumor slides are identified in the top-2 ranked slides for patients with up to 43 slides.

Ayushi Sinha, Shashank Yadav, Benjamin Holmes +9

Department of Radiology, Mayo Clinic, Rochester MN · Department of Radiation Oncology, Mayo Clinic, Rochester MN · AI Program, Mayo Clinic, Rochester MN +4

Computational Pathology Pathology Foundation Models Oncology Whole-Slide Image Analysis

Sep 1, 2026cs.CV

Benchmarking Vision-Language Models for Automated Pathology Diagnosis and Report Generation

The rapid advancement of vision-language models (VLMs) has accelerated progress in computational pathology; however, whole-slide image (WSI)-based pathology report generation remains limited by the scarcity of large-scale WSI--report datasets and the complexity of mapping spatially distributed visual patterns to structured clinical text. To address this, we introduce a clinically curated Pan-Asia WSI--report dataset of approximately 10,500 pairs from five institutions and establish the REG 2025 benchmark through a MICCAI challenge for systematic evaluation of multimodal models. We analyze submitted methods spanning pretrained VLMs, multiple-instance learning frameworks, hierarchical expert models, retrieval-augmented generation, and cross-modal Transformers. Rather than indicating that VLM use alone was sufficient for superior performance, the results suggest that top-performing methods benefited from structured report representations, hierarchical diagnostic decomposition, and effective multimodal grounding. We identify key limitations, including instability in quantitative attribute estimation (e.g., numeric hallucination) and a tendency toward diagnostic overspecification, with some errors resembling known diagnostic pitfalls in routine pathology. These findings establish REG 2025 as a benchmark for evaluating WSI-based structured report generation and vision-language understanding in computational pathology, providing insights for the design of clinically grounded multimodal pathology models.

Yumi Lee, Harim Oh, Hyoryung Kim +52

Computational Pathology Medical VLMs Medical Image Benchmarks Whole-Slide Image Analysis

Sep 1, 2026cs.CV

FTU-Seek: Foundation Model-Guided Hard-Negative Learning for Sparse Functional Tissue Unit Segmentation

Functional tissue units (FTUs), including tertiary lymphoid structures (TLSs), blood vessels, and glands, encode localized immune, vascular, and epithelial organization in histopathology. Accurate quantification of these structures is important for studying tissue architecture and disease-associated tissue organization. However, FTUs are frequently sparse, heterogeneous, and surrounded by large amounts of morphologically similar background tissue, making automated segmentation in whole-slide images (WSIs) challenging. We therefore developed FTU-Seek, a pathology foundation model-guided framework that treats morphology-aware negative-patch selection as a key component of sparse FTU segmentation. FTU-Seek uses frozen multi-depth features from the UNI pathology foundation model to train a patch-level classifier that distinguishes FTU-containing from FTU-absent tissue. Target-absent patches are subsequently ranked according to their predicted target-containing probabilities, and the highest-scoring hard negatives are selected through a static Top

K

strategy to construct compact segmentation training sets. The framework was evaluated using five-fold cross-validation and internal test cohorts across TLS, blood-vessel, and gland segmentation tasks, with an additional independent 30-WSI held-out cohort for TLS. Positive-only, all-tissue, random-negative, and matched random Top

K

sampling strategies served as comparators. Segmentation-derived phenotypes were further explored in external TCGA cohorts.

Zonghao Liu, Lei Su, Jiguang Yu +4

Department of Hepatopancreatobiliary Surgery, Clinical Oncology School, Fujian Medical University, Fuzhou, 350014, China. · Innovation Center for Cancer Research, Clinical Oncology School, Fujian Medical University, Fuzhou, 350014, China. · Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. +5

Histopathology Image Segmentation Whole-Slide Image Analysis

Aug 31, 2026cs.CV

SlideMix: Enhancing Whole Slide Image Analysis via Multimodal Shuffling

Histopathological whole slide images (WSIs) are central to cancer diagnosis, but their gigapixel scale, tissue heterogeneity, weak slide-level supervision, sparse diagnostic regions, and multi-scale evidence make robust automated analysis challenging. Multiple instance learning (MIL) is widely used to aggregate tile-level features into slide-level predictions, yet existing augmentation strategies often perturb tissue regions without preserving diagnostic relevance, slide context, or cross-scale structure. We propose SlideMix, a model-agnostic multimodal augmentation framework for MIL-based WSI analysis. SlideMix uses a retrieval-augmented vision-language model (VLM)-based Visual-Language Adaptive Region selector to identify diagnostically relevant regions and reduce weak-label noise. It then performs In-place Tile Shuffling within meaningful tissue regions to mix feature embeddings while preserving slide-level context. A VLM-based soft-labeling module supervises mixed samples, while a multi-factor, loss-driven online Curriculum-Learning Feedback scheme adaptively controls shuffle granularity, feature similarity, and shuffle ratio to promote cross-scale representation learning. Across 11 WSI datasets comprising 20,523 slides, 8 diagnostic tasks, and 10 WSI backbones, SlideMix improves accuracy and generalization in most settings and compares favorably with established augmentation baselines, providing a simple plug-and-play approach for more robust and scalable digital pathology models. Source code: https://github.com/Xia-Research-Lab/SlideMix

Chad Wong, Sicheng Chen, Tianyi Zhang +4

1Nhu Department of Electrical Engineering and Computer Science, University of California, Irvine · Department of Electrical & Computer Engineering, National University of Singapore · 3PuzzleLogic Pte Ltd, Singapore 229594, Singapore

Data Augmentation Histopathology Image Classification Multiple Instance Learning Whole-Slide Image Analysis

Aug 31, 2026cs.AI

SlideBank: A Persistent Hierarchical Evidence Bank for Consistent Whole-Slide Reasoning

Whole-slide images (WSIs) are challenging for vision-language reasoning because diagnostically relevant morphology is sparse, heterogeneous, and distributed across gigapixel-scale images and multiple spatial resolutions. Existing WSI models and pathology agents can aggregate slide features or actively acquire evidence, but the information retained after exploration is often difficult to access semantically while preserving its connection to the original visual evidence. We introduce SlideBank, a training-free framework that represents each WSI as a persistent, concept-indexed, and spatially grounded evidence bank. SlideBank performs question-independent coarse-to-fine exploration to identify informative regions and multi-scale views, converts them into explicit morphological observations, and grounds pathology signals to their supporting patches and WSI coordinates. At inference time, questions are routed to relevant signals and evidence scales, and the linked global, regional, and patch evidence is integrated through confidence-based cross-level consensus. Experiments on WSI-VQA and SlideBench-BCNB show that with Patho-R1, SlideBank reaches 52.77% on WSI-VQA and with Quilt-LLaVA, it reaches 50.92% average accuracy on SlideBench-BCNB, while structured signal-guided retrieval consistently outperforms random evidence sampling. Reusing the same bank across repeated queries further achieves over 99% rephrasing consistency and substantially reduces amortized inference cost through persistent evidence reuse.

Beidi Zhao, Gexin Huang, Ciro Zhang +6

University of British Columbia · Vector Institute · Harvard University +3

Memory-Augmented VLMs Medical VQA Medical Image Grounding Whole-Slide Image Analysis

Aug 31, 2026cs.CV

Reliable Benchmarking of Artifact Detection in Computational Pathology: A Reproducibility and Uncertainty Analysis

Background and Objective: Quality control is a prerequisite for whole-slide image analysis, yet the benchmarks on which quality-control methods are compared share four properties that make their reported differences hard to interpret: few independent slides, annotation concentrated in a minority of them, pooled ratio metrics with no closed-form standard error, and a single inherited train/test partition. We propose a reliability protocol for such benchmarks. Methods: The protocol quantifies four sources of variability - test-set sampling, training stochasticity, partition composition, and undocumented preprocessing - a claim is reportable only if it survives all four; three of the four cost minutes of compute. We apply it to an independent reconstruction of a published diffusion-based artifact detector, evaluated on the original 24-slide partition and against a supervised baseline. Results: The method's central mechanism reproduces: the auxiliary contrastive term improves pooled F1 from 0.673 to 0.688 and replicates under a second seed (+0.0156, p = 0.031; +0.0190, p = 0.005), although it acts on pen marking rather than the artifact types cited to motivate it. Its comparative claims do not: differences between design variants, and against the supervised baseline, fall inside the uncertainty of the evaluation. Four of 24 slides carry 70% of scored annotated pixels, giving an effective sample size of 6.2, and the inherited partition sits at the 7th percentile. An unreported tissue-restriction step excludes 41.4% of out-of-focus annotation against 2.6% of air bubble; such a gate is confounded with blur by construction. Conclusions: Small-cohort benchmarks support far weaker conclusions than current reporting implies. The four checks are cheap enough to accompany any evaluation on such a resource and separate reproducible effects from differences the evaluation cannot resolve.

Konstantinos Moutselos, Ilias Maglogiannis

Department of Digital Systems, University of Piraeus, Piraeus, Greece

Computational Pathology Uncertainty Quantification Medical Image Benchmarks Whole-Slide Image Analysis

Aug 31, 2026cs.CV

Whole-Slide Image Analysis under Realistic Few-Shot Annotation Protocols

Automating the analysis of whole-slide images has high clinical value, since characterizing cancers requires examining them in detail. Such analysis increasingly relies on vision-language models that provide patch-level zero-shot predictions. However, these predictions remain noisy and must be refined with a few annotations. A promising paradigm for this refinement is few-shot transduction. Rather than treating each patch independently, these methods leverage the relations between patches, together with a few annotations, to refine all predictions jointly. However, current transductive methods are evaluated under conditions that overlook key properties of whole-slide images: (i) datasets consist of independent patches extracted from multiple slides, ignoring the complex tissue organization; (ii) datasets are mostly balanced, whereas a single whole-slide image exhibits severe class imbalance, with several classes absent; and (iii) annotations are sampled at random, without reflecting how a pathologist annotates a limited number of regions. To align the transduction paradigm to realistic whole-slide settings, we introduce the following contributions. First, we propose SlideCRF, which adapts conditional random fields for whole-slide images by combining spatial and biological cues while accounting for classes that may be absent from a given slide. Second, we provide a set of realistic annotation protocols, based on spatially localized clicks and scribbles, modeling different pathologist interactions, such as the iterative correction of model errors. Across four datasets, we show that SlideCRF outperforms current transductive methods in macro F1, improving over the zero-shot predictions by +24.2% and +37.5% with one and 16 clicks per present class, respectively.

Tiffanie Godelaine, Maxime Zanella, Karim El Khoury +2

Institute of Information and Communication Technologies, Electronics, and Applied Mathematics (ICTEAM), Université catholique de Louvain (UCLouvain), 1348 Louvain-la-Neuve, Belgium

Computational Pathology Conditional Random Fields Few-Shot Learning Few-Shot Image Classification Whole-Slide Image Analysis

Aug 10, 2026cs.CV

One Model to Magnify Them All: Efficient Scale-Invariant Histopathology via Conditional Normalization and Continuous Magnification Training

Whole slide images (WSIs) in digital histopathology are acquired at discrete magnification levels encoding complementary diagnostic information from global tissue architecture to fine-grained cellular morphology. Yet, deep learning models remain sensitive to scale variation. Existing magnification-invariant methods rely on multi-scale architectures at predefined discrete resolutions, while in clinical deployment the acquisition magnification varies continuously, rarely aligns with a model's fixed training resolution, and intermediate scales are common, so robust coverage otherwise demands a costly ensemble of magnification-specific models. We propose Conditional Layer Normalization (CLN), a lightweight mechanism that generates affine normalization parameters from input pixel size via a small MLP, integrated into standard CNN architectures for both WSI classification and segmentation. Trained on patches sampled continuously across a range of pixel sizes, the model decouples inference from scanner-dependent magnification and generalizes to arbitrary, previously unseen scales at test time. On the PANDA prostate cancer dataset, our approach on average matches or exceeds independently trained single-magnification models and ranks among the top three performers at every evaluated magnification, including those unseen during training. This collapses a five-model ensemble into a single network and reduces training, and inference cost roughly 4-5 times, while leaving the multiply-accumulate count unchanged. The code is available at: https://github.com/aflorkowska/OneModelToMagnifyThemAll.

Agnieszka Florkowska, Henning Müller, Marek Wodzinski

Sano Centre for Computational Medicine, Krakow, Poland · AGH University of Krakow, al. Adama Mickiewicza 30, 30-059 Kraków, Poland · Institute of Informatics, HES-SO Valais-Wallis, Sierre, Switzerland +1

Computational Pathology Histopathology Image Segmentation Layer Normalization Histopathology Image Classification Whole-Slide Image Analysis

Aug 9, 2026cs.CV

Agentic Visual Reasoning in Whole-Slide Pathology Images via Active Perception

Whole-slide visual reasoning requires identifying sparse diagnostic evidence in gigapixel pathology slides and integrating observations across spatial scales. Existing WSI methods either compress densely sampled patches into global representations or use pretrained vision-language models with heuristic region selection, weakening links between predictions and morphology or lacking pathology-trained observation policies. We present AdaptivePath, an active-perception framework that formulates WSI evidence acquisition as sequential decision making. The Navigator learns question-agnostic abnormality-driven navigation from pathologist-reviewed labels to select observation locations and spatial extents, avoiding costly question-specific trajectory annotations. We train this policy through alternating representation learning and proximal policy optimization, followed by fine-tuning with geometric and appearance consistency objectives to stabilize focus trajectories. During inference, the Navigator hierarchically acquires sparse observations from low to high magnification under a limited ROI budget. A Morphology Interpreter converts observations into question-conditioned evidence, while the Deliberator evaluates evidence and revises intermediate answers across magnifications. The Arbiter integrates deliberation history to produce final answers. AdaptivePath achieves state-of-the-art zero-shot performance on WSI and region pathology VQA benchmarks and reaches 80.14% accuracy for cancer subtype classification across six TCGA cohorts. In a blinded diagnostic-utility study, pathologists using AdaptivePath-selected observation sequences achieve 82.9% accuracy. These results demonstrate that learned active perception enables effective and traceable visual reasoning over gigapixel pathology slides.

Jingyun Chen, Fengchun Liu, Linghan Cai +5

College of Computer Science and Technology, Harbin Institute of Technology, Shenzhen · School of Computing and Data Science, The University of Hong Kong

Active Perception Medical VQA Active View Selection Whole-Slide Image Analysis

Aug 8, 2026cs.CV

Gated Spatial Redundancy Projection for Pathology Transformer Attentions

Transformer models are increasingly used for whole-slide image analysis in computational pathology. Yet, WSIs differ fundamentally from natural images: neighbouring patches often contain highly similar tissue type, stain, texture, and cellular composition. We identify this local spatial redundancy as a pathology-specific failure mode of self-attention, where dominant neighbourhood features can be repeatedly mixed into patch-tokens and weaken subtle diagnostic or prognostic deviations. We propose Gated Spatial Redundancy Projection (Gated SRP), a lightweight drop-in correction module for self-attention layers. For each patch token and attention head, Gated SRP estimates a local redundancy axis from neighbouring value vectors, projects the attention output onto this axis, and applies a learned signed gate to correct the redundancy-aligned component geometrically. Across five TCGA survival cohorts, Gated SRP obtains the highest mean C-index among the compared attention variants in all cohorts, with an average improvement over the base attention, while adding only +0.02% parameters. Across five slide-level classification datasets, it improves the base attention on 12 of 16 reported metrics and achieves the best AUC on three datasets. Code is publicly available at https://github.com/AtlasAnalyticsLab/GatedSRP.

Zhiyuan Yang, Jiahao Cheng, Vincent Quoc-Huy Trinh +1

Department of Computer Science and Software Engineering (CSSE), Concordia University, Montreal, Canada · Axe Cancer, Centre de recherche du CHUM, Université de Montréal, Montréal, Canada · Mila - Quebec AI Institute, Montreal, Canada

Cancer Survival Prediction Self-Attention Attention Mechanisms Histopathology Image Classification Whole-Slide Image Analysis

Aug 6, 2026cs.CV

Beyond Relevance: Bayesian Evidence Acquisition for Agentic Whole-Slide Image Reasoning

Whole-slide image (WSI) reasoning requires an agent to sequentially acquire visual evidence before answering a diagnostic question. Existing training-free agentic frameworks formulate this process as iterative patch retrieval based on semantic relevance to the question. However, semantic relevance does not necessarily imply diagnostic informativeness in computational pathology, where competing diagnoses often exhibit similar and overlapping morphological patterns, making many patches semantically relevant yet diagnostically non-discriminative. Consequently, relevance-based retrieval may acquire redundant observations and leave diagnostic uncertainty unresolved. We propose BEACON, a plug-and-play agentic framework that reformulates WSI reasoning as a Bayesian evidence acquisition problem. BEACON maintains a probabilistic belief over competing diagnostic hypotheses and sequentially acquires patches by maximizing expected information gain (EIG) to reduce diagnostic uncertainty. An evidence controller then determines whether to answer, acquire additional evidence, or perform higher-resolution inspection. Built entirely from off-the-shelf foundation models, BEACON requires no additional training or fine-tuning. Extensive zero-shot experiments across five WSI-VQA benchmarks demonstrate that BEACON achieves the strongest overall performance among training-free agentic frameworks while substantially improving evidence acquisition efficiency, establishing Bayesian evidence acquisition as a principled paradigm for uncertainty-aware agentic WSI reasoning. The code is available at https://github.com/bryanwong17/BEACON

Bryan Wong, Xun Xu, Huazhu Fu +2

1Korea Advanced Institute of Science and Technology (KAIST) · Institute of Advanced Intelligence and Computing (IAIC), A*STAR · Centre for Frontier AI Research (CFAR), A*STAR

Visual Question Answering Computational Pathology Medical VQA Whole-Slide Image Analysis

Aug 5, 2026cs.CV

Bag-of-Visual-Words for Spatial Mapping of Lung Adenocarcinoma Growth Patterns

Spatial mapping of lung adenocarcinoma (LUAD) growth patterns across whole slide images (WSIs) requires resolving architectural context at the region level, yet existing methods operate at the individual tile level and produce generic morphological clusters rather than clinically defined pattern maps. We propose a weakly supervised Bag-of-Visual-Words (BoVW) pipeline that learns a visual vocabulary from frozen foundation model embeddings extracted from a small set of annotated regions of interest (ROIs). Pattern prototypes are constructed as mean BoVW histograms of same-label ROIs and used for nearest-prototype classification of sliding-window regions under Jensen--Shannon divergence. The resulting predictions are projected onto the WSI tile grid to produce interpretable spatial pattern maps. We evaluate the method on 87 CPTAC-LUAD patients using three foundation model encoders and multiple vocabulary sizes on two clinically motivated tasks. For tumour/healthy classification, the best configuration achieves a balanced accuracy of

0.974

with H-Optimus-1, approaching the

0.987

obtained by a supervised SVM trained on mean-pooled WSI embeddings. For binary histologic grade classification, the BoVW pipeline achieves higher balanced accuracy than the supervised baseline for all encoders, suggesting that ROI-level pattern decomposition preserves grade-relevant heterogeneity that is attenuated by global mean pooling.

Darya Ardan, Valentin Oreiller, Henning Müller

Department of Computer Science, University of Geneva, Geneva, Switzerland · Informatics Institute, University of Applied Sciences Western Switzerland (HES-SO Valais), Sierre, Switzerland · Radiology Service, Medical Faculty, University of Geneva, Geneva, Switzerland

Computational Pathology Oncology Histopathology Image Classification Whole-Slide Image Analysis

Aug 4, 2026cs.CV

S $^3$ -Diff: Structural Semantic Synergy Diffusion Model for High Fidelity Super Resolution of Pathological Images

Digital pathology relies on high-resolution whole slide images for accurate diagnosis, yet limitations in imaging devices, storage, and transmission often make lower-resolution pathology images more common in clinical workflows. Current super-resolution techniques often tend to smooth diagnostically relevant morphology, leading to over-smoothed textures and semantic drift that compromise downstream clinical interpretation. To this end, we develop the Structural Semantic Synergy Diffusion Model (S3-Diff), a diffusion framework for high-fidelity super-resolution of pathological images. The core of S3-Diff is Specimen-aware Structural Anchoring (SSA), which combines prognosis-aware tissue support extracted by a fixed SAM with LR-HR gradient discrepancies to generate a specimen-specific structural anchor to preserve pathological morphology. Concurrently, we introduce Structure-guided Semantic Fidelity Tuning (SSFT) to adapt DINOv3 representations using SSA-derived structural supervision. SSFT combines the adapted semantic energy with LR-derived edge and grayscale cues. The resulting control guides denoising to suppress stochastic artifacts and maintain structural consistency. Extensive experimental results demonstrate that S3-Diff consistently outperforms state-of-the-art methods in both reconstruction quality and downstream survival analysis performance. The source code will be made public.

Jiaming Liang, QiHui Han, Guangye Ou +6

South China University of Technology Software Engineering Guangzhou, China · South China University of Technology School of Future Technology Guangzhou, China

Computational Pathology Diffusion Models for Image Restoration Medical Image Super-Resolution Whole-Slide Image Analysis

Aug 4, 2026cs.CV

From Multi-Resolution Cells to Gigapixel Whole Slide Images Foundation Model for Computational Pathology

Vision Transformers (ViTs) and their hierarchical variants have achieved strong performance in Computational Pathology (CPath). However, most are pre-trained on single-resolution Whole Slide Images (WSIs), limiting their generalization across arbitrary resolutions. Gigapixel WSIs inherently contain diagnostic patterns at multiple scales, including cellular morphologies, tissue architectures, and global context, mirroring how expert pathologists examine WSIs. We introduce Multi-Resolution Pyramid Transformer (MRPT), a model that hierarchically aggregates multi-resolution information from cellular to tissue and WSI levels. MRPT employs a biologically meaningful Consecutive Cross-Resolution Attention (CCRA) mechanism to capture scale-independent interactions and enforces multi-resolution semantic consistency by aligning embeddings across resolutions, yielding robust and generalizable WSI representations. Pre-trained in a multi-resolution self-supervised manner on 624M patches, 2.4M regions, and 36K WSIs, MRPT learns rich coarse-to-fine histopathology features. Extensive experiments on 34 diverse datasets show that MRPT surpasses recent foundation models and Multimodal Large Language Models (MLLMs) in cancer subtype classification, tissue phenotyping, and Visual Question Answering (VQA) for WSI understanding.

Basit Alawode, Moshira Ali Abdalla, Dwarikanath Mahapatra +2

Khalifa University of Science and Technology, UAE · University of Western Australia, Australia

Representation Learning Vision Transformer Pathology Foundation Models Histopathology Image Classification Whole-Slide Image Analysis

Aug 4, 2026cs.AI

Spatial proteomics guided by H&E-based AI reveals recurrence-risk niches in triple-negative breast cancer

Deep learning models can predict cancer recurrence from H&E stained slides, but the localized molecular states underlying these predictions remain largely obscured. Here, we developed an outcome informed spatial pathology framework in TNBC that integrates AI generated recurrence risk heatmaps with mass spectrometry based spatial proteomics. In a cohort of 156 patients, distribution based aggregation of high scoring patches achieved an AUC of 0.77 and a C-index of 0.77 in an independent test cohort. Bulk proteomics associated high image derived risk with cell cycle and genome maintenance programs and low risk with immune activation. High and low risk patches coexisted within the same tumor compartment and displayed distinct nuclear and architectural features, revealing intratumoral heterogeneity beyond tissue compartment identity. We then used the heatmaps as coordinate level guides to physically isolate and profile 46 AI defined tumor regions from two recurrence patients. Spatial proteomic profiling revealed a concordant molecular contrast across both patients: mitotic programs were enriched in high risk regions and immune and antigen presentation programs in low risk regions. A 13 protein composite derived from these spatial contrasts showed a trend toward poorer recurrence-free survival with increasing scores in an expanded cohort, while the corresponding transcript based composite stratified recurrence free survival in the independent METABRIC TNBC cohort. Integrating the protein composite with the H&E derived risk score improved the out of bag C-index from 0.679 to 0.739 and enhanced time dependent discrimination at 3 and 5 years. Together, these findings define a new role for outcome trained AI models as spatially explicit experimental guides that connect prognostic morphology with localized molecular states and advance biologically grounded, multiscale biomarker discovery in TNBC.

Yesung Cho, Ji Hwan Park, Chanil Kim +27

OmixAI Co. Ltd., Seoul, Republic of Korea · Meteor Biotech Co. Ltd., Seoul, Republic of Korea · Oncocross Co. Ltd., Seoul, Republic of Korea +4

Breast Cancer Computational Pathology Cancer Survival Prediction Clinical Outcome Prediction Oncology Whole-Slide Image Analysis

Aug 2, 2026cs.CV

Training-Free Out-of-Distribution Detection for Pathology Whole-Slide Images

Safe deployment of AI methods in medicine requires robust guardrails that detect when input data deviate from the training distribution to ensure that models provide predictions only within their scope of expertise and abstain otherwise. Out-of-distribution (OOD) detection can provide such safeguards and is extensively studied in general computer vision. Yet, it remains underdeveloped in computational pathology, where gigapixel whole-slide images (WSIs), subtle differences between disease subtypes, and variability in tissue preparation pose unique challenges for conventional OOD methods. We propose ZIO, a training-free, multimodal OOD detector for pathology WSIs that leverages vision--language pathology foundation models (FMs). ZIO constructs text and visual prototypes of in-distribution classes and integrates their complementary information through a prototype shrinkage mechanism to derive OOD scores. We provide the ZIO formulation for both slide- and patch-level FMs. We evaluate ZIO across diverse clinically relevant domain shifts, including rare diseases and near-OOD settings. Extensive evaluation of over 14,700 WSIs from five independent consortia shows that ZIO consistently outperforms both unimodal prototypes and 40 state-of-the-art OOD methods. These results demonstrate the benefits of multimodal representation for OOD detection and pave the way towards safer AI deployment in clinical practice.

Sabri Mustafa Kahya, Richard R. Chen, Muhammet Sami Yavuz +4

Computational Pathology OOD Detection Whole-Slide Image Analysis

Aug 2, 2026cs.CV

From Patches to Evidence Balls: Class-Conditioned Evidence Retrieval for Few-Shot Whole Slide Image Classification

Whole slide image (WSI) classification is an evidence-driven task, where diagnostic cues are often sparse, spatially organized, and class-dependent. Existing MIL and vision-language methods aggregate a large pool of patch features into a single global slide representation. Under few-shot supervision, limited slide-level labels make it difficult to learn a reliable aggregation mechanism that organizes sparse local cues into compact and coherent diagnostic evidence. Moreover, a shared slide representation compresses evidence supporting a candidate class and its alternatives into the same feature, limiting class-specific reasoning and interpretability. To address these issues, we propose EviBall, a class-conditioned evidence retrieval framework for few-shot WSI classification. EviBall organizes local patches into Evidence Balls through semantic-spatial assignment and center refinement, yielding compact and spatially coherent evidence units under weak supervision. It then uses task-specific class queries, including language-guided queries for morphology-oriented tasks and molecular-guided queries for molecular endpoint prediction, to retrieve supporting evidence balls and produce class-conditioned evidence representations for direct class-wise prediction. By introducing structured evidence units and task-relevant semantic guidance, EviBall reduces the reliance on learning an unconstrained global aggregation mechanism from scarce slide-level labels. It therefore reformulates few-shot WSI classification as structured evidence retrieval and competition among candidate classes. Extensive experiments across four morphology-oriented and molecular endpoint WSI tasks demonstrate that EviBall consistently outperforms conventional and vision-language MIL baselines under diverse few-shot settings, while providing spatially localized and class-specific evidence for each prediction.

Di Zhang, Li Zhang, Jiashuai Liu +9

XJTU · JUFE · University of Cambridge +1

Few-Shot Learning Histopathology Image Classification Multiple Instance Learning Evidence Retrieval Whole-Slide Image Analysis

Aug 1, 2026cs.CV

Zero-Cost Virtual RNA: Approximating Immunotherapy Signatures via Cross-Modal WSI Retrieval

Identifying the

Inflamed'' immunophenotype in Gastric Adenocarcinoma predicts immunotherapy response but requires an expensive 10-gene RNA signature. While deep learning on standard H\&E slides offers a scalable alternative, conventional binary classifiers oversimplify continuous RNA data and introduce label noise. To resolve this, we propose VITA (VIrtual Transcriptomic Approximation). By aligning H\&E and RNA into a joint latent space during training, VITA requires only standard H\&E at inference to retrieve morphologically similar historical cases and approximate the continuous RNA signature. Achieving 0.72 classification accuracy and a 0.66 Spearman correlation, VITA provides a cost-effective

virtual transcriptomics'' pre-screening tool that preserves the continuous phenotypic spectrum without requiring genomic sequencing.

Sigrid Vila-Bagaria, Mar Teixidó, Miquel Piñol +3

Image Processing Group, Universitat Politècnica de Catalunya, Spain · Research group of Cancer Biomarkers & Oncological Pathology, IRB Lleida, Spain

Computational Pathology Cross-Modal Retrieval Oncology Gene Expression Prediction from Histopathology Images Whole-Slide Image Analysis

Jul 30, 2026cs.CV

Beyond Classification: Pathology Foundation Models as Detection Encoders for Mitotic Figures

Pathology foundation models (FMs) are models trained on vast amounts of typically unlabeled data and have been shown to yield regularized latent spaces that can be used effectively in downstream classification tasks. This is also true for the classification of mitotic figures vs. other cells. However, it is so far unclear if the latent space of current FMs provides features that are discriminant and spatially suitably resolved to also serve as a backbone for dense object detection paradigms. In this work, we investigate this question for common current pathology FMs (UNI, UNI2-h, Virchow, Virchow2, H-optimus-0, H-optimus-1) and compare their performance against a fully end-to-end trained baseline based on a ResNet50 architecture. We combine FM backbones with representatives of single stage, dual stage and self-attention-based detectors (RetinaNet, Faster R-CNN, Deformable DETR respectively) on the multi-domain MIDOG++ dataset, and on the TUPAC16 dataset as an out-of-domain case. We show that the H-optimus-0 and Virchow models yielded competitive performance, indicating that the latent spaces of current FMs, all trained on image-level self-supervision, are suitable for direct mitotic figure detection and may be slightly more robust on our out-of-domain test case. All code is made available publicly at https://github.com/DeepMicroscopy/FM4MFdet.

Sweta Banerjee, Alireza Teimoury, Nils Porsche +11

Flensburg University of Applied Sciences, Flensburg, Germany · Julius-Maximilians-Universität Würzburg, Würzburg, Germany · Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany +4

Computational Pathology Pathology Foundation Models Object Detection Whole-Slide Image Analysis

Jul 26, 2026cs.CV

PathSelect: Sequential Token Selection for Whole Slide Pathology

Gigapixel Whole-Slide Images (WSIs) present a fundamental computational bottleneck for vision-language models (VLMs) due to extreme sequence lengths. Existing approaches predominantly rely on spatial sampling or training-free pruning, which risk diluting weak but informative signals, leading to the loss of critical diagnostic evidence due to the spatially diffuse nature of pathological cues. We reformulate WSI token pruning as a sequential selection process, enabling the model to autonomously learn an optimal routing strategy rather than relying on static heuristics. We herein propose a decoupled routing framework integrated as an active plugin into the fully pre-trained SlideChat base model, leaving both the slide encoder and large language model frozen. To provide continuous gradients for the non-differentiable pruning operation during training, we introduce PathSelect. PathSelect employs a variance-preserving noise gate to modulate each patch's information flow via a differentiable Soft Top-K operator, paired with a diagonal-attention Denoiser that recovers the perturbed representations without semantic leakage. At inference, the PathSelect module is entirely detached. Relying solely on the trained Scorer, a deterministic Hard Top-K operator executes adaptive, data-dependent trajectory termination, significantly accelerating downstream generative processing with exceptionally low sequential token selection latency. Driven by an empirical average of only 44.86 tokens under a maximum constraint of K = 128, our framework achieves 74.00% overall accuracy on SlideBench (TCGA), representing an approximate 36.6x spatial token reduction relative to the uncompressed baseline average while consistently outperforming sampling-based counterparts.

Jingzhi Chen, Landi He, Zehong Chen +2

Shenzhen University of Advanced Technology

Efficient VLM Inference Medical VLMs Visual Token Pruning Whole-Slide Image Analysis

Jul 26, 2026cs.CV

Weakly Supervised Instance-Level Gleason Pattern Estimation Using Primary and Secondary Labels

In prostate cancer histopathology, the Gleason Score is determined by the most frequent (Primary) and second most frequent (Secondary) Gleason patterns within a whole-slide image. Although these slide-level labels are routinely available in clinical practice, instance-level Gleason annotations are rarely provided, making patch-level learning challenging. We propose a Multiple Instance Learning (MIL) framework that estimates instance-level Gleason patterns from slide-level Primary and Secondary labels. The proposed method formulates instance-level learning according to the clinical definition of the Gleason Score by aggregating instance predictions into class counts and explicitly modeling the Primary pattern, Secondary pattern, and their dominance. Experimental results demonstrate that the proposed formulation enables effective instance-level learning and outperforms existing MIL approaches on the SICAP-MIL dataset.

Nao Sugeta, Kaito Shiku, Shinnosuke Matsuo +1

Kyushu University, Japan

Weakly Supervised Learning Oncology Multiple Instance Learning Whole-Slide Image Analysis Automated Grading

Jul 21, 2026cs.CV

Pathologist Attention-Aligned Report Generation for Prostate Histopathology

The allocation of visual attention by pathologists during cancer diagnosis is a highly selective process that critically shapes the information extracted from whole-slide images (WSIs). Human attention helps medical imaging tasks such as classification and segmentation, and becomes a strong semantic cue for identifying diagnostically informative regions for report generation. In this paper, we introduce human attention into the training of pathologist report generation models. To this end, we collected a multimodal human-attention dataset of 121 prostate WSIs annotated with pathologists' multi-scale viewport trajectories synchronized with the pathologists' verbal descriptions and cursor movements for five clinically relevant components (e.g., Gleason patterns). Using this dataset, we finetune two report generation models with an attention-alignment loss that regularizes the model attention over image patches to match the distribution of pathologist attention. We evaluate our approach on prostate cancer report generation and visual question answering using two models with different internal attention mechanisms (i.e., how image tokens are integrated into the language decoder). Experiments show average gains of 10.9% on NLP-based metrics and 19.3% in accuracy across five clinically relevant report components. Further, model attention maps extracted at inference time, with minimal computational overhead, align more closely with pathologist attention, providing stronger visual support for the generated reports by highlighting the regions that most influence the output.

Ruoyu Xue, Suryakant Singh, Souradeep Chakraborty +12

Department of Computer Science, Stony Brook University, USA · Department of Biomedical Informatics, Stony Brook University, USA · Université Paris-Saclay, CentraleSupélec, Gustave Roussy, INSERM, IHU PRISM, Cancer Data Science Unit, France +4

Computational Pathology Medical Report Generation Medical VQA Oncology Whole-Slide Image Analysis

Jul 21, 2026cs.CV

PathAgentBench: Benchmarking Evidence-Seeking Vision-Language Models on Whole-Slide Pathology Image

Whole-slide image (WSI) diagnosis requires identifying diagnostically relevant regions, examining them across magnifications, and integrating multi-scale evidence. However, most existing pathology benchmarks evaluate models on pre-cropped patches or pre-extracted slide features, leaving their ability to acquire evidence directly from gigapixel WSIs largely untested. We introduce PathAgentBench, a benchmark for evaluating evidence-seeking vision-language models (VLMs) across four complementary capabilities: image-to-text matching for evidence interpretation, text-to-image retrieval for evidence verification, diagnostic-region localization for evidence acquisition, and multi-scale reasoning for evidence integration. The benchmark is organized as a diagnostic tree that links nested regions across magnifications with scale-specific findings and path-level diagnoses. It contains 1,822 TCGA WSIs and 17,135 diagnostic paths annotated by ten board-certified pathologists. An additional private cohort of 190 breast cancer WSIs with detailed annotations is used to evaluate autonomous whole-slide exploration. We evaluate 20 general-purpose, medical, and pathology-specialized models. Leading open-weight models achieve over 93% accuracy in multi-scale reasoning and over 50% accuracy in both cross-modal matching tasks. In contrast, diagnostic-region localization remains challenging: the best text-guided mean intersection-over-union is below 0.09, underperforming a simple center-based heuristic. During autonomous exploration, the unconditional hit rate decreases from 0.522 at low magnification to 0.185 at intermediate magnification and 0.020 at high magnification. These results reveal a pronounced gap between reasoning over curated evidence and acquiring that evidence directly from WSIs. PathAgentBench provides a unified framework for measuring and improving evidence-seeking pathology models.

Dankai Liao, Tianyi Zhang, Yufeng Wu +6

Department of Biomedical Engineering, National University of Singapore, Singapore 117417, Singapore

VLM Evaluation Medical VLMs Medical Image Localization Medical Image Benchmarks Whole-Slide Image Analysis

Jul 20, 2026cs.CL

PathReportEval: A Systematic Benchmark for Pathology Report Generation

Pathology report generation from whole-slide images (WSIs) is a rapidly growing multimodal learning problem, yet progress is difficult to measure because existing studies use heterogeneous datasets, model settings, visual encoders, and evaluation protocols. Moreover, commonly used natural language generation metrics, including BLEU, ROUGE, and METEOR, primarily reward lexical similarity and often fail to detect clinically consequential errors such as omitted diagnoses, hallucinated findings, or discordant tumor attributes. We present a standardized benchmark and evaluation framework for pathology report generation. The benchmark evaluates four representative methods across three datasets (TCGA, HistAI, and REG 2025) using three pathology foundation encoders (CONCHv1.5, UNI2-h, and H-Optimus-1). Our framework standardizes preprocessing, feature extraction, training, decoding, and evaluation, enabling fair comparison across models while providing a modular platform for integrating new methods, datasets, and encoders. A central contribution is the Clinical Report Quality Score (CRQS), a clinically grounded metric for evaluating factual correctness. CRQS maps reference and generated reports into structured clinical attributes and measures four complementary dimensions: clinical fact coverage, key information recall, hallucination rate, and clinical discordance, producing both an overall score and interpretable sub-scores. Experiments demonstrate that conventional language-generation metrics are weakly aligned with clinical correctness and frequently overestimate report quality. In contrast, CRQS reveals clinically meaningful differences between models and encoders that lexical metrics fail to capture. Together, the benchmark, public plug-and-play framework, and CRQS establish a reproducible foundation for rigorous evaluation of pathology report generation.

Suryakant Singh, Sejuti Majumder, Beatrice Knudsen +2

Department of Biomedical Informatics Stony Brook University Stony Brook, NY, USA · Department of Pathology University of Utah Salt Lake City, UT, USA

Medical Report Generation Medical Image Benchmarks Whole-Slide Image Analysis

Jul 20, 2026cs.CV

GigaPath-Flash and GigaTIME-Flash: Efficient Pathology Foundation Models for Whole-Slide and Tumor Microenvironment Analysis

Foundation models have emerged as a driving force in computational pathology, with the potential to transform cancer diagnosis, prognosis, and treatment selection by learning transferable representations from large-scale histopathology data. A growing landscape of pathology foundation models now spans diverse data sources, architectures, and downstream applications. However, most pretrained models operate only at the image-tile level, use restrictive licenses, and remain computationally expensive, limiting large-scale slide-level clinical and research use. Here, we introduce GigaPath-Flash and GigaTIME-Flash, efficient models for whole-slide pathology AI and spatial proteomics prediction. GigaPath-Flash combines a 22M-parameter ViT-S tile encoder with a 21M-parameter LongNet slide encoder, both pretrained on large-scale real-world histopathology data. Its compact tile encoder is distilled from the billion-parameter GigaPath (ViT-g) teacher and shared by both models. GigaPath-Flash retains 97% of GigaPath's average slide-level performance with 50x less compute. GigaTIME-Flash extends this backbone to predict the tumor immune microenvironment directly from routine H&E images. It surpasses the original CNN-based GigaTIME in prediction quality while running 6x faster and using 8x less GPU memory. Together with GigaPath and GigaTIME, these models form an open-weight, Apache-2.0-licensed family pretrained on large-scale real-world clinical data. By releasing all models and weights, we provide accessible building blocks for computational pathology, immuno-oncology, and precision health.

Naoto Usuyama, Jeya Maria Jose Valanarasu, Sicong Yao +27

Microsoft Research · Paul G. Allen School of Computer Science and Engineering, University of Washington · Providence Genomics +2

Pathology Foundation Models Oncology Whole-Slide Image Analysis

Jul 16, 2026cs.CV

Pretraining Multiple Instance Learning Networks with Multi-Teacher Distillation from Pathology Slide Foundation Models

Multiple instance learning (MIL) has become the main paradigm for whole-slide image (WSI) analysis in computational pathology. However, existing MIL aggregators are still typically trained from scratch for each downstream task, relying on limited slide-level labels to learn both aggregation mechanisms and downstream discriminative representations simultaneously. As a result, they often suffer from unstable optimization, overfitting, and limited transferability. Similar to pretrained ResNet and Vision Transformer models in natural image learning, MIL also requires reusable pretrained initialization. However, high-quality slide-level pretraining data remain scarce, and MIL models are usually lightweight and weakly supervised, making large-scale pretraining difficult in practice. To address this challenge, we propose a distillation-based pretraining framework for MIL, which leverages two slide-level foundation models, TITAN and CARE, as teachers to transfer their representational knowledge into a diverse set of MIL architectures. To effectively balance supervision from different teachers, we further introduce an angular dispersion normalized distillation loss. The distilled weights are then used as initialization for downstream adaptation. We conduct systematic evaluations on 15 benchmark datasets under both linear probing and full-parameter fine-tuning, and further validate its advantages in few-shot scenarios. Experimental results show that pretraining generally improves MIL aggregators over from scratch training, especially in linear-probing and few-shot settings, while maintaining the computational efficiency of lightweight MIL models. Code is available at https://github.com/fu0201/MIL_Pretrained.

Mingxi Fu, Jiawen Li, Renao Yan +4

Tsinghua Shenzhen International Graduate School, Tsinghua University · University of Washington · City University of Hong Kong (Dongguan) +2

Multi-Teacher Knowledge Distillation Multiple Instance Learning Whole-Slide Image Analysis

Jul 14, 2026cs.CV

CGRL: Concept-Guided Pruning and Representation Learning for Whole-Slide Image Classification

Weakly supervised whole-slide image (WSI) classification is widely used in computational pathology because slide-level labels are easier to obtain than dense region annotations. Existing multiple instance learning (MIL) methods often aggregate large bags of patch embeddings using mainly visual cues, which can retain many non-informative patches and provide weak alignment between instance features and class-level disease semantics. We propose Concept-Guided Pruning and Representation Learning (CGRL), a simple framework that introduces class-level concept prototypes derived from disease prompts into the MIL pipeline. First, concept-relevance pruning ranks patch instances by their similarity to class concepts and retains the top-K concept-relevant patches for downstream MIL aggregation. Second, concept-guided contrastive representation learning constructs class-wise positive and negative patch sets from the same similarity matrix and optimizes target-class, symmetric auxiliary, and cross-class separation objectives, thereby regularizing the projected concept space. We evaluate CGRL on TCGA-BRCA and TCGA-NSCLC using multiple representative MIL methods. Experimental results show that CGRL improves several model-dataset combinations, with gains depending on the downstream MIL model and dataset. It achieves particularly clear improvements in accuracy and macro-F1 while reducing computational cost through concept-relevance pruning. These findings demonstrate that class-level semantic concepts provide an effective and practical prior for patch selection and representation learning in weakly supervised computational pathology.

Thuc Huynh, Tuan Le, Doanh C. Bui

University of Information Technology, Ho Chi Minh City, Vietnam · Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam

Computational Pathology Contrastive Learning Weakly Supervised Learning Multiple Instance Learning Whole-Slide Image Analysis

Jul 14, 2026cs.CV

Demonstration of the common dual-channel feature decoupling characteristic of front-door mediation causal inference methods in whole-slice image classification

Causal inference using front door intervention and multi-instance learning (MIL) has advanced the analysis of Whole Slide Images (WSI) in digital pathology. These methods adjust feature distributions of subtle evidence sub-images to correctly associate them with WSI-level diagnoses. We propose and prove 2 hypotheses for evaluating such methods: 1) Causal inference MIL introduces an independent classification channel that effectively completes WSI classification; 2) Greater difference between features extracted by the new and baseline channels increases effectiveness in eliminating false correlations. This hypothesis describes the core of causal inference MILs: overlaying parallel, independent channels to eliminate false associations between WSI-level diagnostic and non-diagnostic evidence sub-images by increasing deep feature diversity. Based on these hypotheses, we evaluated several causal inference MILs on breast cancer and non-small cell lung cancer datasets. This hypothesis provides a new theoretical perspective for applying causal inference to WSI analysis.

Zhirui Zhang, Tianhang Nan, Yong Ding +3

College of Medicine and Biological Information Engineering, Northeastern University, China

Representation Disentanglement Histopathology Image Classification Causal Inference Multiple Instance Learning Whole-Slide Image Analysis

Jul 14, 2026cs.CV

Auditing Data Leakage in Whole-Slide Image Multimodal Benchmarks

Recent vision-language models (VLMs) for computational pathology report striking zero-shot performance on whole-slide image (WSI) visual question answering (VQA) benchmarks. We audit these claims and find them fundamentally compromised by data leakage at two hierarchical levels: patient-level leakage, where slides from the same case appear in both training and test folds, and institutional-level leakage, where different cases nonetheless share staining-batch and scanner signatures through a common Tissue Source Site (TSS). By tracing canonical slide, case, and TSS identifiers across major public resources, we document case level train test overlaps of 92.3~100% on TCGA-derived benchmarks, together with near-complete TSS overlap. We further demonstrate that both leakage levels are linearly decodable from foundation-model feature space, that they induce a measurable accuracy gap between leaked and audit-clean cases on a published checkpoint, and that across multiple published WSI VLMs, peak reported accuracies concentrate on the most heavily contaminated benchmarks. Therefore, the current WSI VQA evaluation cannot distinguish genuine multimodal reasoning from nearest-neighbor retrieval over memorized institutional and patient-specific artifacts. Finally, we outline concrete recommendations for contamination-free evaluation. By addressing benchmark construction, provenance disclosure, and automated overlap auditing, we aim to guide future research toward verifiable claims of progress.

Wenhao Zhang, Zhongliang Zhou, John Kang +1

University of Virginia · Merck & Co., Inc.

VLM Evaluation Data Leakage Medical VQA Medical Image Benchmarks Whole-Slide Image Analysis

Jul 12, 2026cs.CV

Toward Efficient Weakly Supervised Semantic Segmentation Using Only Low-Magnification Histopathological Images

Whole-slide images (WSIs) provide rich tissue-level and cellular-level information, but storing and transmitting high-magnification pathology data is resource-intensive. Moreover, annotating WSIs at the pixel level is labor-intensive and time-consuming. Therefore, it is important to investigate whether low-magnification pathology images with limited annotations (i.e., image-level instead of pixel-level labels) can achieve performance comparable to high-magnification images. This paper presents a systematic benchmark study on weakly supervised histopathological image segmentation under different low-resolution storage settings. Starting from high-resolution image patches, we simulate lower-magnification inputs and reconstruct them to the original size using interpolation and deep learning-based reconstruction methods before applying the weakly-supervised segmentation pipeline. This framework enables a quantitative evaluation of how weakly supervised methods respond to different levels of resolution degradation. Experimental results show that reconstruction quality metrics alone are insufficient to predict downstream segmentation performance. In particular, the study identifies a critical degradation point where the localization of small-scale structures declines significantly. These findings provide practical guidance for designing efficient digital pathology storage systems while maintaining reliable automated analysis. Code is available at https://github.com/Dung-Dx/LowMagWSS

Dung Minh Do, Nhat-Thanh Huynh, Duc Minh Huynh +2

University of Information Technology, Ho Chi Minh City, Vietnam · Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam

Weakly Supervised Image Segmentation Histopathology Image Segmentation Weakly Supervised Semantic Segmentation Medical Image Segmentation Whole-Slide Image Analysis

Jul 11, 2026cs.CV

TVT-PAPD: Pathology-Aware Prototype Distillation for Self-Supervised Whole Slide Image Classification

Self-supervised learning (SSL) has emerged as an effective paradigm for learning transferable representations from large-scale unlabeled whole slide images (WSIs). However, existing SSL methods primarily learn generic visual features and often fail to explicitly capture pathology-specific morphological patterns that are critical for disease characterization. To address this limitation, we propose Tiny Vision Transformer with Pathology-Aware Prototype Distillation (TVT-PAPD). This self-supervised pathology representation learning framework integrates a Tiny Vision Transformer (TVT) with a novel Pathology-Aware Prototype Distillation (PAPD) module. PAPD employs a learnable pathology prototype bank to discover and preserve representative tissue morphology patterns, encouraging semantically similar pathological regions to learn consistent and discriminative representations. The proposed framework enhances pathology-aware feature learning while maintaining computational efficiency with 90M parameters. Experiments on the Cancer Genome Atlas (TCGA) low-grade glioma (LGG)/glioblastoma (GBM) dataset and the Indian Pathology Brain (IPD-Brain) dataset demonstrate that TVT-PAPD achieves weighted F1-scores of 93.02% and 90.23%, respectively, for LGG-GBM classification, while exhibiting strong cross-cohort generalization across independent glioma datasets.

Ramesh Naidu Laveti, Jaya Sreevalsan-Nair, T K Srikanth

E-Health Research Center, International Institute of Information Technology Bangalore, Karnataka 560100, India.

Prototype Learning Histopathology Image Classification Brain Tumor Classification Medical Image Representation Learning Whole-Slide Image Analysis

Jul 10, 2026cs.CV

ALICE: Learning a General-Purpose Pathology Foundation Model from Vision, Vision-Language, and Slide-Level Experts

Foundation models are reshaping computational pathology, yet their capabilities remain shaped by pretraining objectives, data sources, and spatial scales, fragmenting complementary expertise across separate backbones. Here we present ALICE, a unified foundation model trained through multi-stage agglomerative distillation that sequentially distills eight vision-only, vision-language, and slide-level teacher models into dedicated modules of a single backbone. ALICE is pretrained on 24,985,184 tile-level pathology images and 155,604 high-resolution images, and evaluated across 21 task scenarios, 96 downstream tasks, and 48 data sources, spanning region-of-interest tissue analysis, vision-language multimodal evaluation, and whole-slide clinical assessment. In all three evaluation settings, ALICE achieved the best average rank among task-matched pathology foundation models. These results demonstrate that agglomerative distillation can consolidate complementary capabilities from specialized models into a unified backbone for broad computational pathology applications. The model is available at https://github.com/WonderLandxD/ALICE.

Jiawen Li, Tian Guan, Huijuan Shi +5

Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China · Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China · Department of Engineering Science, University of Oxford, Oxford, UK +1

Computational Pathology Unified Multimodal Models Pathology Foundation Models Multi-Teacher Knowledge Distillation Multimodal Foundation Models Whole-Slide Image Analysis

Jul 10, 2026eess.IV

Slide-Level Active Learning Reduces Annotation Burden in H&E images

Deep learning-based segmentation of histopathology whole-slide images (WSIs) requires large amounts of pixel-level annotations, which are costly and time-consuming to obtain. Active learning (AL) has been proposed to reduce this effort, but existing methods exhibit three key limitations. Uncertainty estimation is unreliable on partially annotated WSIs, patch-level acquisition is inconsistent with slide-level annotation workflows, and class imbalance in multi-class settings is not explicitly addressed. To address these challenges, we propose SHAL (Slide-level Hybrid Active Learning), a patient-level AL framework for annotation-efficient multi-class histopathology segmentation. SHAL integrates three complementary components: a foreground-aware strategy that suppresses bias from unlabeled background regions, a stage-adaptive mechanism that hybridizes predictive entropy and epistemic uncertainty across learning stages, and a class-aware strategy that prioritizes diagnostically relevant tissue classes. SHAL is evaluated on the TCGA colorectal cancer dataset. It achieves the highest Macro Dice at the full annotation budget (0.846) and reaches Dice greater than or equal to 0.80 using only 26 percent of the budget (50 of 190 slides), whereas competing methods reach this threshold only at 37 percent (70 slides). Across five independent external cohorts, SHAL attains the highest mean external Macro Dice (0.815) and the smallest internal-to-external generalization gap among all methods (0.025 at Round 3 and 0.026 at the full budget). The results indicate that patient-level hybrid uncertainty acquisition reduces annotation cost without sacrificing cross-domain generalization in computational pathology.

Mahsa Vali, Zhilong Weng, Noémie Moreaua +2

Institute for Biomedical Informatics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany · Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany · Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany +3

Computational Pathology Histopathology Image Segmentation Medical Image Segmentation Whole-Slide Image Analysis

Jul 9, 2026cs.CV

ProsMAE: Multi-Source MAE Pretraining for ISUP Grade Classification

Whole slide images (WSIs) provide rich diagnostic information for computational pathology, but their gigapixel scale, stain variation, scanner differences, tissue artifacts, and limited expert annotation make robust model training challenging. This paper presents a multi-source Masked Autoencoder (MAE) framework, named ProsMAE, for histopathology representation learning. Tiles from Prostate cANcer graDe Assessment (PANDA), CAncer MEtastases in LYmph nOdes challeNge 2017 (CAMELYON17), and BReAst Carcinoma Subtyping (BRACS) are used for ProsMAE pretraining to expose the encoder to diverse tissue morphology and acquisition conditions. The learned encoder is transferred for International Society of Urological Pathology (ISUP) grade classification through ProsCLS, using a frozen encoder and a linear classification head. ProsMAE achieved a higher mean validation quadratic weighted kappa (QWK) than the vanilla MAE frozen linear-probe baseline under the evaluated disjoint PANDA split. Repeated-split evaluation remains necessary to further establish robustness across split compositions.

Anna Jung, Kyeonghun Kim, Youngung Han +6

SNU · OUTTA · GIST +1

Computational Pathology Masked Autoencoders Oncology Histopathology Image Classification Medical Image Representation Learning Whole-Slide Image Analysis

Jul 6, 2026cs.CV

Continual Model Merging with Test-Time Adaptation for Whole-Slide Image Analysis

Model merging offers a practical alternative to conventional continual learning by integrating independently fine-tuned models without retaining previous training data. Recent state-of-the-art model merging methods employ test-time adaptation (TTA-guided merging) to address distribution shifts by adjusting merging-related variables using unlabeled target data. However, these methods have primarily been studied in multi-task or single-target settings, and their behavior under sequential continual learning remains insufficiently understood. We present a benchmark study that maps this family of methods to rehearsal-free continual Whole Slide Image classification and evaluates them against traditional continual-learning approaches. Experiments on six TCGA cancer-subtyping cohorts cover CLASS-IL and TASK-IL scenarios, in-domain and out-of-domain evaluation, and different task orders. The results show that adapting model merging at test time can provide strong task-specific performance and improve retention of previously acquired knowledge without storing historical WSIs. Nevertheless, performance remains sensitive to task order and to the interaction between adaptation on the current distribution and accumulated knowledge. This benchmark identifies model merging with test-time adaptation as a promising direction for continual computational pathology and motivates future methods that balance adaptation to domain shift with explicit preservation of historical knowledge.

Duc-Thanh Le, Doanh C. Bui, Maï K. Nguyen +1

University of Information Technology · 2Viet Nam National University Ho Chi Minh City · 3ETIS (UMR 8051), CY Cergy Paris University, ENSEA, CNRS, France

Continual Test-Time Adaptation Histopathology Image Classification Whole-Slide Image Analysis

Jul 6, 2026cs.CV

MergeSurv: Merging-Based Continual Learning for Survival Analysis on Whole-Slide Images

Survival analysis on Whole Slide Images (WSIs) is important in computational pathology for prognosis estimation and treatment planning. However, existing survival models are typically trained independently for each cancer cohort, making continual adaptation computationally expensive for gigapixel-scale WSIs. In this study, we propose MergeSurv, a merging-based continual learning framework for WSI survival analysis. A pathology vision-language foundation model is independently fine-tuned on each task, and the learned parameters are sequentially merged into a unified model without storing previous training data. We further investigate two inference strategies: One-for-All (OFA) and Voting-Expert Aggregation (VEA). Experiments on four TCGA cohorts demonstrate that MergeSurv outperforms naive fine-tuning as well as representative regularization-based and rehearsal-based continual learning methods, while effectively reducing catastrophic forgetting. The results suggest that model merging is a promising direction for scalable and privacy-preserving continual learning in computational pathology.

Vu Minh Tran, Doanh C. Bui, Maï K. Nguyen +1

University of Information Technology · 2Viet Nam National University Ho Chi Minh City · 3ETIS (UMR 8051), CY Cergy Paris University, ENSEA, CNRS, France

Cancer Survival Prediction Survival Analysis Continual Learning Oncology Model Merging Whole-Slide Image Analysis

Jul 4, 2026cs.CV

Paired Uterine Whole-Slide Images and Pathology Reports for Multimodal Computational Pathology

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 dataset underwent a structured multi-stage validation procedure involving board-certified pathologists to ensure reliable annotations. TUM-Uteria supports research in computational pathology, including whole-slide image analysis, multimodal learning, and automated pathology report generation.

Han Li, Jingsong Liu, Ayako Ura +14

Institute of Pathology, Technical University of Munich, Munich, Germany · 2Computer Aided Medical Procedures (CAMP), Technical University of Munich, Munich, Germany · 6Munich Center for Machine Learning (MCML), Munich, Germany +4

Computational Pathology Medical Report Generation Whole-Slide Image Analysis

Jul 1, 2026cs.CV

Prior-Anchored Debiasing for Long-Tailed Multi-Organ Pathology Report Generation

Automated pathology report generation from Whole Slide Images (WSIs) has attracted increasing attention in digital pathology. However, existing methods are predominantly developed under single-organ settings, overlooking the multi-organ scenarios encountered in clinical practice, where organ types typically follow a long-tailed distribution. To address this gap, we identify two critical biases: (1) visual representation bias, where the encoder favors head-class patterns over tail-class discriminative features, and (2) textual decoding bias, where the decoder overfits to head-class narrative patterns, yielding diagnostically unreliable outputs for tail-class organs. To mitigate these two biases, we propose a novel Prior-anchored multi-Organ pathology report Generation framework (PriOrGen). Specifically, a Visual-Prototype Anchored Bottleneck module leverages the information bottleneck principle with learnable anchor representations to selectively retain diagnostically relevant visual information while filtering out head-biased redundancy. Secondly, a Meta-Report Anchored Bank module constructs an organ-specific meta-report anchored bank and retrieves organ-faithful textual priors to steer the decoder away from head-class narrative patterns. Extensive experiments on a multi-organ pathology dataset demonstrate that our method effectively mitigates long-tail biases and achieves superior report generation performance across both head and tail organ categories compared to state-of-the-art methods.

Feng Yang, Jie Liu, Yubo Pang +5

City University of Hong Kong, Hong Kong SAR · University of Nottingham, United Kingdom · University of Massachusetts Boston, United States

Medical Report Generation Long-Tail Learning Whole-Slide Image Analysis