Whole-Slide Image Analysis

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Whole-slide image analysis studies how to extract clinically useful information from gigapixel tissue scans, where relevant cells and tissue patterns may be sparse and spread across multiple scales. Common approaches divide slides into patches and use multiple-instance learning with slide-level labels, while newer methods add spatial graphs, multiscale models, pathology foundation models, or vision-language systems. These methods support tasks such as cancer classification, grading, lesion and cell localization, survival prediction, molecular profiling, and report generation. A central challenge is balancing accuracy and clinically grounded evidence with computational cost and reliable generalization across hospitals, scanners, and patient cohorts.

Latest papers

214 papers35 papers in the last four weeks, up 75% on the four weeks before. 0.2% of all new papers.

Mar 10, 2026

PathMem: Toward Cognition-Aligned Memory Transformation for Pathology MLLMs

Computational pathology demands both visual pattern recognition and dynamic integration of structured domain knowledge, including taxonomy, grading criteria, and clinical evidence. In practice, diagnostic reasoning requires linking morphological evidence with formal diagnostic and grading criteria. Although multimodal large language models (MLLMs) demonstrate strong vision language reasoning capabilities, they lack explicit mechanisms for structured knowledge integration and interpretable memory control. As a result, existing models struggle to consistently incorporate pathology-specific diagnostic standards during reasoning. Inspired by the hierarchical memory process of human pathologists, we propose PathMem, a memory-centric multimodal framework for pathology MLLMs. PathMem organizes structured pathology knowledge as a long-term memory (LTM) and introduces a Memory Transformer that models the dynamic transition from LTM to working memory (WM) through multimodal memory activation and context-aware knowledge grounding, enabling context-aware memory refinement for downstream reasoning. PathMem achieves SOTA performance across benchmarks, improving WSI-Bench report generation (12.8% WSI-Precision, 10.1% WSI-Relevance) and open-ended diagnosis by 9.7% and 8.9% over prior WSI-based models.

Jinyue Li, Yuci Liang, Qiankun Li +7

University of Science and Technology of China · Shenzhen University · Nanyang Technological University +2

Memory-Augmented VLMs Medical VLMs Computational Pathology Multimodal Memory Whole-Slide Image Analysis

Mar 9, 2026

A Lightweight Multi-Cancer Tumor Localization Framework for Deployable Digital Pathology

Accurate localization of tumor regions from hematoxylin and eosin-stained whole-slide images is fundamental for translational research including spatial analysis, molecular profiling, and tissue architecture investigation. However, deep learning-based tumor detection trained within specific cancers may exhibit reduced robustness when applied across different tumor types. We investigated whether balanced training across cancers at modest scale can achieve high performance and generalize to unseen tumor types. A multi-cancer tumor localization model (MuCTaL) was trained on 79,984 non-overlapping tiles from four cancers (melanoma, hepatocellular carcinoma, colorectal cancer, and non-small cell lung cancer) using transfer learning with DenseNet169. The model achieved a tile-level ROC-AUC of 0.97 in validation data from the four training cancers, and 0.71 on an independent pancreatic ductal adenocarcinoma cohort. A scalable inference workflow was built to generate spatial tumor probability heatmaps compatible with existing digital pathology tools. Code and models are publicly available at https://github.com/AivaraX-AI/MuCTaL.

Brian Isett, Rebekah Dadey, Aofei Li +5

UPMC Hillman Cancer Center, Pittsburgh, PA, USA · Malignant Hematology and Medical Oncology Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA · Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA +2

Medical Image Localization Computational Pathology Whole-Slide Image Analysis Cross-Domain Generalization

Mar 6, 2026

MoEMambaMIL: Structure-Aware Selective State Space Modeling for Whole-Slide Image Analysis

Whole-slide image (WSI) analysis is challenging due to the gigapixel scale of slides and their inherent hierarchical multi-resolution structure. Existing multiple instance learning (MIL) approaches often model WSIs as unordered collections of patches, which limits their ability to capture structured dependencies between global tissue organization and local cellular patterns. Although recent State Space Models (SSMs) enable efficient modeling of long sequences, how to structure WSI tokens to fully exploit their spatial hierarchy remains an open problem.We propose MoEMambaMIL, a structure-aware SSM framework for WSI analysis that integrates region-nested selective scanning with mixture-of-experts (MoE) modeling. Leveraging multi-resolution preprocessing, MoEMambaMIL organizes patch tokens into region-aware sequences that preserve spatial containment across resolutions. On top of this structured sequence, we decouple resolution-aware encoding and region-adaptive contextual modeling via a combination of static, resolution-specific experts and dynamic sparse experts with learned routing. This design enables efficient long-sequence modeling while promoting expert specialization across heterogeneous diagnostic patterns. Experiments demonstrate that MoEMambaMIL achieves the best performance across 9 downstream tasks.

Dongqing Xie, Yonghuang Wu

Tongji University · Fudan University

Whole-Slide Image Analysis Multiple Instance Learning Visual SSMs

Mar 4, 2026

RANGER: Sparsely-Gated Mixture-of-Experts with Adaptive Retrieval Re-ranking for Pathology Report Generation

Pathology report generation remains a relatively under-explored downstream task, primarily due to the gigapixel scale and complex morphological heterogeneity of Whole Slide Images (WSIs). Existing pathology report generation frameworks typically employ transformer architectures, relying on a homogeneous decoder architecture and static knowledge retrieval integration. Such architectures limit generative specialization and may introduce noisy external guidance during the report generation process. To address these limitations, we propose RANGER, a sparsely-gated Mixture-of-Experts (MoE) framework with adaptive retrieval re-ranking for pathology report generation. Specifically, we integrate a sparsely gated MoE into the decoder, along with noisy top-

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routing and load-balancing regularization, to enable dynamic expert specialization across various diagnostic patterns. Additionally, we introduce an adaptive retrieval re-ranking module that selectively refines retrieved memory from a knowledge base before integration, reducing noise and improving semantic alignment based on visual feature representations. We perform extensive experiments on the PathText-BRCA dataset and demonstrate consistent improvements over existing approaches across standard natural language generation metrics. Our full RANGER model achieves optimal performance on PathText dataset, reaching BLEU-1 to BLEU-4 scores of 0.4598, 0.3044, 0.2036, and 0.1435, respectively, with METEOR of 0.1883, and ROUGE-L of 0.3038, validating the effectiveness of dynamic expert routing and adaptive knowledge refinement for semantically grounded pathology report generation.

Yixin Chen, Ziyu Su, Hikmat Khan +1

Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA · Department of Pathology, The Ohio State University, Columbus, OH, USA

Medical Report Generation Multimodal RAG Mixture-of-Experts Models Whole-Slide Image Analysis

Mar 4, 2026

WSI-INR: Implicit Neural Representations for Lesion Segmentation in Whole-Slide Images

Whole-slide images (WSIs) are fundamental for computational pathology, where accurate lesion segmentation is critical for clinical decision making. Existing methods partition WSIs into discrete patches, disrupting spatial continuity and treating multi-resolution views as independent samples, which leads to spatially fragmented segmentation and reduced robustness to resolution variations. To address the issues, we propose WSI-INR, a novel patch-free framework based on Implicit Neural Representations (INRs). WSI-INR models the WSI as a continuous implicit function mapping spatial coordinates directly to tissue semantics features, outputting segmentation results while preserving intrinsic spatial information across the entire slide. In the WSI-INR, we incorporate multi-resolution hash grid encoding to regard different resolution levels as varying sampling densities of the same continuous tissue, achieving a consistent feature representation across resolutions. In addition, by jointly training a shared INR decoder, WSI-INR can capture general priors across different cases. Experimental results showed that WSI-INR maintains robust segmentation performance across resolutions; at Base/4, our resolution-specific optimization improves Dice score by +26.11%, while U-Net and TransUNet decrease by 54.28% and 36.18%, respectively. Crucially, this work enables INRs to segment highly heterogeneous pathological lesions beyond structurally consistent anatomical tissues, offering a fresh perspective for pathological analysis.

Yunheng Wu, Wenqi Huang, Liangyi Wang +4

Graduate School of Informatics, Nagoya University, Nagoya, Japan · Chair for AI in Healthcare and Medicine, Technical University of Munich (TUM) and TUM University Hospital, Munich, Germany · School of Computation and Information Technology, Technical University of Munich, Munich, Germany +4

Image Segmentation Histopathology Image Segmentation Whole-Slide Image Analysis Implicit Neural Representations

Mar 3, 2026

BRIGHT: A Collaborative Generalist-Specialist Foundation Model for Breast Pathology

Generalist pathology foundation models (PFMs), pretrained on large-scale multi-organ datasets, have demonstrated remarkable predictive capabilities across diverse clinical applications. However, their proficiency on the full spectrum of clinically essential tasks within a specific organ system remains an open question due to the lack of large-scale validation cohorts for a single organ as well as the absence of a tailored training paradigm that can effectively translate broad histomorphological knowledge into the organ-specific expertise required for specialist-level interpretation. In this study, we propose BRIGHT, the first PFM specifically designed for breast pathology, trained on over 51,000 breast whole-slide images derived from a cohort of over 40,000 patients across 19 hospitals. BRIGHT employs a collaborative generalist-specialist framework to capture both universal and organ-specific features. To comprehensively evaluate the performance of PFMs on breast oncology, we curate the largest multi-institutional cohorts to date for downstream task development and evaluation, comprising over 25,000 WSIs across 10 hospitals. The validation cohorts cover the full spectrum of breast pathology across 25 distinct clinical tasks spanning diagnosis, biomarker prediction, treatment response and survival prediction. Extensive experiments demonstrate that BRIGHT outperforms five leading generalist PFMs, achieving state-of-the-art (SOTA) performance in 25 of 25 internal validation tasks and in 4 of 11 external validation tasks with excellent heatmap interpretability. By evaluating on large-scale validation cohorts, this study not only demonstrates BRIGHT's clinical utility in breast oncology but also validates a collaborative generalist-specialist paradigm, providing a scalable template for developing PFMs on a specific organ system, accelerating the translation of foundation models into ...

Xiaojing Guo, Jiatai Lin, Yumian Jia +39

Breast Cancer Healthcare Pathology Foundation Models Oncology Whole-Slide Image Analysis

Mar 2, 2026

MMNavAgent: Multi-Magnification WSI Navigation Agent for Clinically Consistent Whole-Slide Analysis

Recent AI navigation approaches aim to improve Whole-Slide Image (WSI) diagnosis by modeling spatial exploration and selecting diagnostically relevant regions, yet most operate at a single fixed magnification or rely on predefined magnification traversal. In clinical practice, pathologists examine slides across multiple magnifications and selectively inspect only necessary scales, dynamically integrating global and cellular evidence in a sequential manner. This mismatch prevents existing methods from modeling cross-magnification interactions and adaptive magnification selection inherent to real diagnostic workflows. To these, we propose a clinically consistent Multi-Magnification WSI Navigation Agent (MMNavAgent) that explicitly models multi magnification interaction and adaptive magnification selection. Specifically, we introduce a Cross-Magnification navigation Tool (CMT) that aggregates contextual information from adjacent magnifications to enhance discriminative representations along the navigation path. We further introduce a Magnification Selection Tool (MST) that leverages memory-driven reasoning within the agent framework to enable interactive and adaptive magnification selection, mimicking the sequential decision process of pathologists. Extensive experiments on a public dataset demonstrate improved diagnostic performance, with 1.45% gain of AUC and 2.93% gain of BACC over a non-agent baseline. Code will be public upon acceptance.

Zhengyang Xu, Han Li, Jingsong Liu +10

Institute of Pathology, Technical University of Munich, Germany · Munich Center for Machine Learning (MCML), Munich, Germany · Computer Aided Medical Procedures (CAMP), TU Munich, Munich, Germany +7

Whole-Slide Image Analysis Computational Pathology

Mar 2, 2026

QCAgent: An agentic framework for quality-controllable pathology report generation from whole slide image

Recent methods for pathology report generation from whole-slide image (WSI) are capable of producing slide-level diagnostic descriptions but fail to ground fine-grained statements in localized visual evidence. Furthermore, they lack control over which diagnostic details to include and how to verify them. Inspired by emerging agentic analysis paradigms and the diagnostic workflow of pathologists,who selectively examine multiple fields of view, we propose QCAgent, an agentic framework for quality-controllable WSI report generation. The core innovations of this framework are as follows: (i) it incorporates a customized critique mechanism guided by a user-defined checklist specifying required diagnostic details and constraints; (ii) it re-identifies informative regions in the WSI based on the critique feedback and text-patch semantic retrieval, a process that iteratively enriches and reconciles the report. Experiments demonstrate that by making report requirements explicitly prompt-defined, constraint-aware, and verifiable through evidence-grounded refinement, QCAgent enables controllable generation of clinically meaningful and high-coverage pathology reports from WSI.

Rundong Wang, Wei Ba, Ying Zhou +8

School of Biomedical Engineering, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, P.R. China · Center for Medical Imaging, Robotics, Analytic Computing & Learning (MIRACLE), Suzhou Institute for Advance Research, USTC, 215123, P.R. China · Chinese PLA General Hospital Ninth Medical Center, China +1

Medical Report Generation Computational Pathology Whole-Slide Image Analysis Controllable Text Generation Agentic Workflows

Mar 1, 2026

ASMIL: Attention-Stabilized Multiple Instance Learning for Whole Slide Imaging

Attention-based multiple instance learning (MIL) has emerged as a powerful framework for whole slide image (WSI) diagnosis, leveraging attention to aggregate instance-level features into bag-level predictions. Despite this success, we find that such methods exhibit a new failure mode: unstable attention dynamics. Across four representative attention-based MIL methods and two public WSI datasets, we observe that attention distributions oscillate across epochs rather than converging to a consistent pattern, degrading performance. This instability adds to two previously reported challenges: overfitting and over-concentrated attention distribution. To simultaneously overcome these three limitations, we introduce attention-stabilized multiple instance learning (ASMIL), a novel unified framework. ASMIL uses an anchor model to stabilize attention, replaces softmax with a normalized sigmoid function in the anchor to prevent over-concentration, and applies token random dropping to mitigate overfitting. Extensive experiments demonstrate that ASMIL achieves up to a 6.49% F1 score improvement over state-of-the-art methods. Moreover, integrating the anchor model and normalized sigmoid into existing attention-based MIL methods consistently boosts their performance, with F1 score gains up to 10.73%. All code and data are publicly available at https://github.com/Linfeng-Ye/ASMIL.

Linfeng Ye, Shayan Mohajer Hamidi, Zhixiang Chi +5

University of Toronto · Stanford University · Hokkaido University

Multiple Instance Learning Whole-Slide Image Analysis Histopathology Image Classification

Mar 1, 2026

TC-SSA: Token Compression via Semantic Slot Aggregation for Gigapixel Pathology Reasoning

The application of large vision-language models to computational pathology holds great promise for diagnostic assistants but faces a critical computational bottleneck: the gigapixel scale of Whole Slide Images (WSIs). A single WSI typically contains over 105 patches, creating sequence lengths that exceed the constraints of standard Transformer architectures. Existing solutions often resort to spatial sampling, which risks discarding diagnostically critical evidence. To address this, we propose TC-SSA (Token Compression via Semantic Slot Aggregation), a learnable token compression framework that aggregates patch features into a fixed number of semantic slots. A gated routing module assigns patches to slots using sparse Top-2 routing, followed by weighted aggregation, enabling global slide coverage under a strict token budget. The resulting representation retains diagnostically relevant information while reducing the number of visual tokens to 1.7% of the original sequence. On the SlideBench(TCGA), our model achieves 78.34% overall accuracy and 77.14% on the diagnosis subset, outperforming sampling-based baselines under comparable token budgets. The method also generalizes to MIL classification, reaching AUC of 95.83% on TCGA-BRCA, 98.27% on TCGA-NSCLC and 79.80% on PANDA. These results suggest that learnable semantic aggregation provides an effective trade-off between efficiency and diagnostic performance for gigapixel pathology reasoning.

Zhuo Chen, Shawn Young, Lijian Xu

Shenzhen University of Advanced Technology Shenzhen, Guangdong, China · University of Nottingham NingBo China NingBo, ZheJiang, China FoSE, Department of Mathematics with Applied Mathematics

Visual Token Compression Whole-Slide Image Analysis Computational Pathology Histopathology Image Classification

Feb 28, 2026

Act Like a Pathologist: Tissue-Aware Whole Slide Image Reasoning

Computational pathology has advanced rapidly in recent years, driven by domain-specific image encoders and growing interest in using vision-language models to answer natural-language questions about diseases. Yet, the core problem behind pathology question-answering remains unsolved, considering that a gigapixel slide contains far more information than necessary for a given question. Pathologists naturally navigate tissue and morphology complexity by scanning broadly, and zooming in selectively according to the clinical questions. Current models, in contrast, rely on uniform patch sampling or broad attention maps, often attending equally to irrelevant regions while overlooking key visual evidence. In this work, we try to bring models closer to how humans actually examine slides. We propose a question-guided, tissue-aware, and coarse-to-fine retrieval framework, HistoSelect, that consists of two key components: a group sampler that identifies question-relevant tissue regions, followed by a patch selector that retrieves the most informative patches within those regions. By selecting only the most informative patches, our method becomes significantly more efficient: reducing visual token usage by 70% on average, while improving accuracy across three pathology QA tasks. Evaluated on 356,000 question-answer pairs, our approach outperforms existing methods and produces answers grounded in interpretable, pathologist-consistent regions. Our results suggest that bringing human-like search and attention patterns into WSI reasoning is a promising direction for building practical and reliable pathology VLMs. Code is available at https://github.com/winston52/HistoSelect.

Wentao Huang, Weimin Lyu, Peiliang Lou +8

Stony Brook University, NY, USA · Mayo Clinic, MN, USA · Harvard Medical School, MA, USA +1

Pathology VQA Medical VQA Medical VLMs Whole-Slide Image Analysis

Feb 28, 2026

Hierarchical Classification for Improved Histopathology Image Analysis

Whole-slide image analysis is essential for diagnostic tasks in pathology, yet existing deep learning methods primarily rely on flat classification, ignoring hierarchical relationships among class labels. In this study, we propose HiClass, a hierarchical classification framework for improved histopathology image analysis, that enhances both coarse-grained and fine-grained WSI classification. Built based upon a multiple instance learning approach, HiClass extends it by introducing bidirectional feature integration that facilitates information exchange between coarse-grained and fine-grained feature representations, effectively learning hierarchical features. Moreover, we introduce tailored loss functions, including hierarchical consistency loss, intra- and inter-class distance loss, and group-wise cross-entropy loss, to further optimize hierarchical learning. We assess the performance of HiClass on a gastric biopsy dataset with 4 coarse-grained and 14 fine-grained classes, achieving superior classification performance for both coarse-grained classification and fine-grained classification. These results demonstrate the effectiveness of HiClass in improving WSI classification by capturing coarse-grained and fine-grained histopathological characteristics.

Keunho Byeon, Jinsol Song, Seong Min Hong +2

School of Electrical Engineering, Korea University, Seoul, Korea · Department of Hospital Pathology, The Catholic University of Korea College of Medicine, Seoul, Korea

Histopathology Image Classification Hierarchical Classification Whole-Slide Image Analysis Hierarchical Representation Learning Multiple Instance Learning

Feb 27, 2026

Margin-Consistent Deep Subtyping of Invasive Lung Adenocarcinoma via Perturbation Fidelity in Whole-Slide Image Analysis

Whole-slide image classification for invasive lung adenocarcinoma subtyping remains vulnerable to real-world imaging perturbations that undermine model reliability at the decision boundary. We propose a margin consistency framework evaluated on 203,226 patches from 143 whole-slide images spanning five adenocarcinoma subtypes in the BMIRDS-LUAD dataset. By combining attention-weighted patch aggregation with margin-aware training, our approach achieves robust feature-logit space alignment measured by Kendall correlations of 0.88 during training and 0.64 during validation. Contrastive regularization, while effective at improving class separation, tends to over-cluster features and suppress fine-grained morphological variation; to counteract this, we introduce Perturbation Fidelity (PF) scoring, which imposes structured perturbations through Bayesian-optimized parameters. Vision Transformer-Large achieves 95.20 +/- 4.65% accuracy, representing a 40% error reduction from the 92.00 +/- 5.36% baseline, while ResNet101 with an attention mechanism reaches 95.89 +/- 5.37% from 91.73 +/- 9.23%, a 50% error reduction. All five subtypes exceed an area under the receiver operating characteristic curve (AUC) of 0.99. On the WSSS4LUAD external benchmark, ResNet50 with an attention mechanism attains 80.1% accuracy, demonstrating cross-institutional generalizability despite approximately 15-20% domain-shift-related degradation and identifying opportunities for future adaptation research.

Meghdad Sabouri Rad, Junze, Huang +6

Vincent · Department of Pathology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA. · Columbia University, New York, NY, 10027, USA.

Histopathology Image Classification Cancer Subtype Classification Whole-Slide Image Analysis Computational Pathology Consistency Regularization

Feb 27, 2026

Footprint-Guided Exemplar-Free Continual Histopathology Report Generation

Rapid progress in vision-language modeling has enabled pathology report generation from gigapixel whole-slide images, but most approaches assume static training with simultaneous access to all data. In clinical deployment, however, new organs, institutions, and reporting conventions emerge over time, and sequential fine-tuning can cause catastrophic forgetting. We introduce an exemplar-free continual learning framework for WSI-to-report generation that avoids storing raw slides or patch exemplars. The core idea is a compact domain footprint built in a frozen patch-embedding space: a small codebook of representative morphology tokens together with slide-level co-occurrence summaries and lightweight patch-count priors. These footprints support generative replay by synthesizing pseudo-WSI representations that reflect domain-specific morphological mixtures, while a teacher snapshot provides pseudo-reports to supervise the updated model without retaining past data. To address shifting reporting conventions, we distill domain-specific linguistic characteristics into a compact style descriptor and use it to steer generation. At inference, the model identifies the most compatible descriptor directly from the slide signal, enabling domain-agnostic setup without requiring explicit domain identifiers. Evaluated across multiple public continual learning benchmarks, our approach outperforms exemplar-free and limited-buffer rehearsal baselines, highlighting footprint-based generative replay as a practical solution for deployment in evolving clinical settings.

Pratibha Kumari, Daniel Reisenbüchler, Afshin Bozorgpour +3

Faculty of Informatics and Data Science, University of Regensburg, Germany · Indian Institute of Information Technology Bhopal, India

Medical Report Generation Continual Learning for VLMs Replay-Based Continual Learning Whole-Slide Image Analysis

Feb 26, 2026

Hierarchical Multi-Scale Graph Learning with Knowledge-Guided Attention for Whole-Slide Image Survival Analysis

We propose a Hierarchical Multi-scale Knowledge-aware Graph Network (HMKGN) that models multi-scale interactions and spatially hierarchical relationships within whole-slide images (WSIs) for cancer prognostication. Unlike conventional attention-based MIL, which ignores spatial organization, or graph-based MIL, which relies on static handcrafted graphs, HMKGN enforces a hierarchical structure with spatial locality constraints, wherein local cellular-level dynamic graphs aggregate spatially proximate patches within each region of interest (ROI) and a global slide-level dynamic graph integrates ROI-level features into WSI-level representations. Moreover, multi-scale integration at the ROI level combines coarse contextual features from broader views with fine-grained structural representations from local patch-graph aggregation. We evaluate HMKGN on four TCGA cohorts (KIRC, LGG, PAAD, and STAD; N=513, 487, 138, and 370) for survival prediction. It consistently outperforms existing MIL-based models, yielding improved concordance indices (10.85% better) and statistically significant stratification of patient survival risk (log-rank p < 0.05).

Bin Xu, Yufei Zhou, Boling Song +6

Nanjing University of Information Science and Technology, Nanjing, China · Case Western Reserve University, Cleveland, OH, USA · Georgia Institute of Technology and Emory University, Atlanta, GA, USA +4

Hierarchical GNNs Cancer Survival Prediction Whole-Slide Image Analysis Computational Pathology Multi-Scale Feature Fusion

Feb 25, 2026

CARE: A Molecular-Guided Foundation Model with Adaptive Region Modeling for Whole Slide Image Analysis

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

Di Zhang, Zhangpeng Gong, Xiaobo Pang +14

Xi’an Jiaotong University · University of Cambridge · KingMed +2

Pathology Foundation Models Whole-Slide Image Analysis Multimodal Foundation Models Gene Expression Prediction from Histopathology Images

Feb 24, 2026

MUSE: Harnessing Precise and Diverse Semantics for Few-Shot Whole Slide Image Classification

In computational pathology, few-shot whole slide image classification is primarily driven by the extreme scarcity of expert-labeled slides. Recent vision-language methods incorporate textual semantics generated by large language models, but treat these descriptions as static class-level priors that are shared across all samples and lack sample-wise refinement. This limits both the diversity and precision of visual-semantic alignment, hindering generalization under limited supervision. To overcome this, we propose the stochastic MUlti-view Semantic Enhancement (MUSE), a framework that first refines semantic precision via sample-wise adaptation and then enhances semantic richness through retrieval-augmented multi-view generation. Specifically, MUSE introduces Sample-wise Fine-grained Semantic Enhancement (SFSE), which yields a fine-grained semantic prior for each sample through MoE-based adaptive visual-semantic interaction. Guided by this prior, Stochastic Multi-view Model Optimization (SMMO) constructs an LLM-generated knowledge base of diverse pathological descriptions per class, then retrieves and stochastically integrates multiple matched textual views during training. These dynamically selected texts serve as enriched semantic supervisions to stochastically optimize the vision-language model, promoting robustness and mitigating overfitting. Experiments on three benchmark WSI datasets show that MUSE consistently outperforms existing vision-language baselines in few-shot settings, demonstrating that effective few-shot pathology learning requires not only richer semantic sources but also their active and sample-aware semantic optimization. Our code is available at: https://github.com/JiahaoXu-god/CVPR2026_MUSE.

Jiahao Xu, Sheng Huang, Xin Zhang +3

School of Big Data & Software Engineering, Chongqing University · School of Computer Science & Technology, Chongqing University

Computational Pathology Medical VLMs Whole-Slide Image Analysis

Feb 23, 2026

Exploiting Label-Independent Regularization from Spatial Dependencies for Whole Slide Image Analysis

Whole slide images, with their gigapixel-scale panoramas of tissue samples, are pivotal for precise disease diagnosis. However, their analysis is hindered by immense data size and scarce annotations. Existing MIL methods face challenges due to the fundamental imbalance where a single bag-level label must guide the learning of numerous patch-level features. This sparse supervision makes it difficult to reliably identify discriminative patches during training, leading to unstable optimization and suboptimal solutions. We propose a spatially regularized MIL framework that leverages inherent spatial relationships among patch features as label-independent regularization signals. Our approach learns a shared representation space by jointly optimizing feature-induced spatial reconstruction and label-guided classification objectives, enforcing consistency between intrinsic structural patterns and supervisory signals. Experimental results on multiple public datasets demonstrate significant improvements over state-of-the-art methods, offering a promising direction.

Weiyi Wu, Xinwen Xu, Chongyang Gao +3

1Dartmouth College · 2Massachusetts General Hospital · 3Northwestern University

Whole-Slide Image Analysis Multiple Instance Learning Histopathology Image Classification

Feb 23, 2026

Hepato-LLaVA: An Expert MLLM with Sparse Topo-Pack Attention for Hepatocellular Pathology Analysis on Whole Slide Images

Hepatocellular Carcinoma diagnosis relies heavily on the interpretation of gigapixel Whole Slide Images. However, current computational approaches are constrained by fixed-resolution processing mechanisms and inefficient feature aggregation, which inevitably lead to either severe information loss or high feature redundancy. To address these challenges, we propose Hepato-LLaVA, a specialized Multi-modal Large Language Model designed for fine-grained hepatocellular pathology analysis. We introduce a novel Sparse Topo-Pack Attention mechanism that explicitly models 2D tissue topology. This mechanism effectively aggregates local diagnostic evidence into semantic summary tokens while preserving global context. Furthermore, to overcome the lack of multi-scale data, we present HepatoPathoVQA, a clinically grounded dataset comprising 33K hierarchically structured question-answer pairs validated by expert pathologists. Our experiments demonstrate that Hepato-LLaVA achieves state-of-the-art performance on HCC diagnosis and captioning tasks, significantly outperforming existing methods. Our code and implementation details are available at https://pris-cv.github.io/Hepto-LLaVA/.

Yuxuan Yang, Zhonghao Yan, Yi Zhang +6

School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing 100876, China · Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

Pathology VQA Medical VLMs Whole-Slide Image Analysis Medical VQA Histopathology Image Classification

Feb 21, 2026

AINet: Anchor Instances Learning for Regional Heterogeneity in Whole Slide Image

Recent advances in multi-instance learning (MIL) have witnessed impressive performance in whole slide image (WSI) analysis. However, the inherent sparsity of tumors and their morphological diversity lead to obvious heterogeneity across regions, posing significant challenges in aggregating high-quality and discriminative representations. To address this, we introduce a novel concept of anchor instance (AI), a compact subset of instances that are representative within their regions (local) and discriminative at the bag (global) level. These AIs act as semantic references to guide interactions across regions, correcting non-discriminative patterns while preserving regional diversity. Specifically, we propose a dual-level anchor mining (DAM) module to select AIs from massive instances, where the most informative AI in each region is extracted by assessing its similarity to both local and global embeddings. Furthermore, to ensure completeness and diversity, we devise an anchor-guided region correction (ARC) module that explores the complementary information from all regions to correct each regional representation. Building upon DAM and ARC, we develop a concise yet effective framework, AINet, which employs a simple predictor and surpasses state-of-the-art methods with substantially fewer FLOPs and parameters. Moreover, both DAM and ARC are modular and can be seamlessly integrated into existing MIL frameworks, consistently improving their performance.

Tingting Zheng, Hongxun Yao, Kui Jiang +2

Harbin Institute of Technology · Tsinghua University · Zhengzhou University

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

Feb 21, 2026

Initialization matters in few-shot adaptation of vision-language models for histopathological image classification

Vision language models (VLM) pre-trained on datasets of histopathological image-caption pairs enabled zero-shot slide-level classification. The ability of VLM image encoders to extract discriminative features also opens the door for supervised fine-tuning for whole-slide image (WSI) classification, ideally using few labeled samples. Slide-level prediction frameworks require the incorporation of multiple instance learning (MIL) due to the gigapixel size of the WSI. Following patch-level feature extraction and aggregation, MIL frameworks rely on linear classifiers trained on top of the slide-level aggregated features. Classifier weight initialization has a large influence on Linear Probing performance in efficient transfer learning (ETL) approaches based on few-shot learning. In this work, we propose Zero-Shot Multiple-Instance Learning (ZS-MIL) to address the limitations of random classifier initialization that underperform zero-shot prediction in MIL problems. ZS-MIL uses the class-level embeddings of the VLM text encoder as the classification layer's starting point to compute each sample's bag-level probabilities. Through multiple experiments, we demonstrate the robustness of ZS-MIL compared to well-known weight initialization techniques both in terms of performance and variability in an ETL few-shot scenario for subtyping prediction.

Pablo Meseguer, Rocío del Amor, Valery Naranjo

Instituto Universitario de Investigación en Tecnología Centrada en el Ser Humano (HUMAN-Tech), Universitat Politècnica de Valencia, Valencia, Spain · Valencian Graduate School and Research Network for Artificial Intelligence (valgrAI), Valencia, Spain

Histopathology Image Classification VLM Adaptation Few-Shot Image Classification Whole-Slide Image Analysis Multiple Instance Learning

Feb 18, 2026

Automated Histopathology Report Generation via Pyramidal Feature Extraction and the UNI Foundation Model

Generating diagnostic text from histopathology whole slide images (WSIs) is challenging due to the gigapixel scale of the input and the requirement for precise, domain specific language. We propose a hierarchical vision language framework that combines a frozen pathology foundation model with a Transformer decoder for report generation. To make WSI processing tractable, we perform multi resolution pyramidal patch selection (downsampling factors 2^3 to 2^6) and remove background and artifacts using Laplacian variance and HSV based criteria. Patch features are extracted with the UNI Vision Transformer and projected to a 6 layer Transformer decoder that generates diagnostic text via cross attention. To better represent biomedical terminology, we tokenize the output using BioGPT. Finally, we add a retrieval based verification step that compares generated reports with a reference corpus using Sentence BERT embeddings; if a high similarity match is found, the generated report is replaced with the retrieved ground truth reference to improve reliability.

Ahmet Halici, Ece Tugba Cebeci, Musa Balci +2

ViseurAI

Medical Report Generation Medical VLMs Whole-Slide Image Analysis

Feb 17, 2026

Context-aware Skin Cancer Epithelial Cell Classification with Scalable Graph Transformers

Whole-slide images (WSIs) from cancer patients contain rich information that can be used for medical diagnosis or to follow treatment progress. To automate their analysis, numerous deep learning methods based on convolutional neural networks and Vision Transformers have been developed and have achieved strong performance in segmentation and classification tasks. However, due to the large size and complex cellular organization of WSIs, these models rely on patch-based representations, losing vital tissue-level context. We propose using scalable Graph Transformers on a full-WSI cell graph for classification. We evaluate this methodology on a challenging task: the classification of healthy versus tumor epithelial cells in cutaneous squamous cell carcinoma (cSCC), where both cell types exhibit very similar morphologies and are therefore difficult to differentiate for image-based approaches. We first compared image-based and graph-based methods on a single WSI. Graph Transformer models SGFormer and DIFFormer achieved balanced accuracies of

85.2 \pm 1.5

(

\pm

standard error) and

85.1 \pm 2.5

in 3-fold cross-validation, respectively, whereas the best image-based method reached

81.2 \pm 3.0

. By evaluating several node feature configurations, we found that the most informative representation combined morphological and texture features as well as the cell classes of non-epithelial cells, highlighting the importance of the surrounding cellular context. We then extended our work to train on several WSIs from several patients. To address the computational constraints of image-based models, we extracted four

2560 \times 2560

pixel patches from each image and converted them into graphs. In this setting, DIFFormer achieved a balanced accuracy of

83.6 \pm 1.9

(3-fold cross-validation), while the state-of-the-art image-based model CellViT256 reached

78.1 \pm 0.5

.

Lucas Sancéré, Noémie Moreau, Katarzyna Bozek

Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, North Rhine-Westphalia, Germany · Institute for Biomedical Informatics, Faculty of Medicine and University Hospital Cologne, University of Cologne, North Rhine-Westphalia, Germany · Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, North Rhine-Westphalia, Germany +1

Computational Pathology Oncology Histopathology Image Classification Graph Transformer Whole-Slide Image Analysis

Feb 16, 2026

Prototype Instance-semantic Disentanglement with Low-rank Regularized Subspace Clustering for WSIs Explainable Recognition

The tumor region plays a key role in pathological diagnosis. Tumor tissues are highly similar to precancerous lesions and non tumor instances often greatly exceed tumor instances in whole slide images (WSIs). These issues cause instance-semantic entanglement in multi-instance learning frameworks, degrading both model representation capability and interpretability. To address this, we propose an end-to-end prototype instance semantic disentanglement framework with low-rank regularized subspace clustering, PID-LRSC, in two aspects. First, we use secondary instance subspace learning to construct low-rank regularized subspace clustering (LRSC), addressing instance entanglement caused by an excessive proportion of non tumor instances. Second, we employ enhanced contrastive learning to design prototype instance semantic disentanglement (PID), resolving semantic entanglement caused by the high similarity between tumor and precancerous tissues. We conduct extensive experiments on multicentre pathology datasets, implying that PID-LRSC outperforms other SOTA methods. Overall, PID-LRSC provides clearer instance semantics during decision-making and significantly enhances the reliability of auxiliary diagnostic outcomes.

Chentao Li, Pan Huang

Whole-Slide Image Analysis Histopathology Image Classification Explainable Medical Image Analysis Multiple Instance Learning Clustering

Feb 3, 2026

AtlasPatch: Scalable Foundation Model-based Tissue Detection and Patch Extraction for Computational Pathology

Whole-slide image (WSI) preprocessing, including tissue detection and patch extraction, is critical computational pathology, yet remains a major bottleneck for large-scale workflows. Existing methods often rely either on threshold-based heuristics that are sensitive to staining variations, tissue fragmentation, and artifacts, or on patch-wise deep learning pipelines with substantially higher computational cost. We present AtlasPatch, a scalable high-throughput WSI preprocessing method built around a foundation-model-based tissue detector that operates at thumbnail resolution: a single thumbnail-level forward pass yields a tissue mask that directly guides patch coordinate generation at the target desired magnification, avoiding repeated patch-level inference. The proposed detector's robustness and efficiency is driven by two coupled contributions: (i) a parameter-efficient adaptation of the SAM2 foundation model that updates only its layer-normalization parameters (0.076% of model weights), and (ii) a curated and semi-manually annotated multi-cohort dataset of 30,000 WSI thumbnail-mask pairs deliberately spanning multiple organs, scanners, tissue appearances, and artifacts. The detector is coupled with pyramid-aware contour mapping from thumbnail to full-resolution slide coordinates, enabling direct patch coordinate generation at the target magnification and parallelized high-throughput patch extraction. AtlasPatch's tissue detection achieves a precision of 0.986 and remains robust across slide variations. Compared with widely used deep-learning preprocessing methods, AtlasPatch is up to 16x faster while preserving downstream multiple-instance learning performance across six slide-level classification tasks. These results position AtlasPatch as a frontier of efficient preprocessing in large-scale computational pathology and pathology foundation models.

Ahmed Alagha, Christopher Leclerc, Yousef Kotp +12

Department of Computer Science and Software Engineering (CSSE), Concordia University, Montreal, QC, Canada, H3G 1M8 · Concordia Institute for Information Systems Engineering (CIISE), Concordia University, Montreal, QC, Canada, H3G 1M8 · Mila–Quebec AI Institute, Montreal, QC, Canada, H2S 3H1 +5

Computational Pathology Whole-Slide Image Analysis Histopathology Image Segmentation Segment Anything Models

Feb 2, 2026

Toxicity Assessment in Preclinical Histopathology via Class-Aware Mahalanobis Distance for Known and Novel Anomalies

Drug-induced toxicity is a leading cause of preclinical and early-clinical failure, making early detection critical. Histopathology is the gold standard for toxicity assessment but relies on expert pathologists, creating a bottleneck for large-scale screening. We introduce an AI-based anomaly detection framework for whole-slide images (WSIs) of rodent liver that identifies healthy tissue and known pathologies (anomalies) and flags samples without training data as out-of-distribution (OOD). We evaluate OOD detection on two held-out categories: apoptosis (single-cell, near-OOD) and staining/processing artifacts (heterogeneous, far-OOD). We build a novel pixelwise-annotated dataset and fine-tune a pre-trained Vision Transformer (DINOv2) via Low-Rank Adaptation (LoRA) for segmentation, then use the Mahalanobis distance for OOD detection with class-specific thresholds. Optimizing the false positive rate subject to a predefined constraint on the false negative rate yields only 0.16% of pathological tissue classified as healthy and 0.35% of healthy tissue classified as pathological. Our false negative rate does not penalise cross-type errors, reflecting the safety-first objective of never overlooking a lesion; under the stricter correct-class criterion our method assigns 93.93% of ID and 89.38% of OOD findings to their own class. The study demonstrates technical feasibility of pixel-level anomaly detection for mouse liver histopathology, indicating possible applications in improving preclinical workflows and drug development efficiency.

Olga Graf, Dhrupal Patel, Peter Groß +3

Tübingen AI Center, University of Tübingen, Tübingen, Germany · Toxicologic Pathologist, Gujarat, India · Boehringer Ingelheim Pharma GmbH and Co., Biberach an der Riß, Germany +1

Histopathology Image Segmentation Mahalanobis Distance Medical Image Anomaly Detection Toxicity Detection OOD Detection Whole-Slide Image Analysis

Jan 6, 2026

LSP-DETR: Efficient and Scalable Nuclei Segmentation in Whole-Slide Images

Background and Objective: Precise and scalable instance segmentation of cell nuclei is a fundamental prerequisite for computational pathology, yet gigapixel whole-slide images (WSIs) pose significant computational challenges. While patch-based processing is standard during training, existing methods are often limited to small tile sizes during inference due to architectural bottlenecks or reliance on computationally expensive post-processing for instance separation. We introduce a faster, scalable, and end-to-end framework capable of processing large-scale image tiles while accurately modeling biologically realistic overlapping nuclei. Methods: We propose LSP-DETR (Local Star Polygon DEtection TRansformer). The model represents nuclei as star-convex polygons and employs a lightweight transformer with linear complexity, enabling the processing of high-resolution images in a single forward pass. A novel radial distance loss accommodates annotation uncertainty, allowing the segmentation of overlapping nuclei to emerge naturally without explicit overlap labels. Results: LSP-DETR achieves state-of-the-art efficiency, with an inference time of 0.45 s/mm^2, a 3.2x speedup over StarDist, the next-fastest method. On PanNuke, the model achieves competitive accuracy (67.5 bPQ), while yielding an F

_1

-score of 0.964 in polygon overlap when evaluated against consensus annotations from two expert pathologists. Furthermore, it outperforms larger models such as LKCell in generalization robustness, reaching an F1-score of 85.0 on MoNuSeg. Conclusions: LSP-DETR bridges the gap between high-fidelity segmentation and practical clinical requirements by eliminating heuristic post-processing. By providing a scalable, linear-complexity solution that naturally handles overlaps between nuclei, this framework sets a new direction for efficient high-throughput WSI analysis in digital pathology.

Matěj Pekár, Vít Musil, Rudolf Nenutil +2

Masaryk University, Faculty of Informatics, Botanická 68a, Brno, 602 00, Czech Republic · Masaryk Memorial Cancer Institute, Žlutý kopec 7, Brno, 656 53, Czech Republic · BBMRI-ERIC, Neue Stiftingtalstraße 2/B/6, Graz, 8010, Austria

Computational Pathology Image Segmentation Histopathology Image Segmentation Instance Segmentation Detection Transformer Whole-Slide Image Analysis

Dec 19, 2025

PathFLIP: Fine-grained Language-Image Pretraining for Versatile Computational Pathology

While Vision-Language Models (VLMs) have achieved notable progress in computational pathology (CPath), the gigapixel scale and spatial heterogeneity of Whole Slide Images (WSIs) continue to pose challenges for multimodal understanding. Existing alignment methods struggle to capture fine-grained correspondences between textual descriptions and visual cues across thousands of patches from a slide, compromising their performance on downstream tasks. In this paper, we propose PathFLIP (Pathology Fine-grained Language-Image Pretraining), a novel framework for holistic WSI interpretation. PathFLIP decomposes slide-level captions into region-level subcaptions and generates text-conditioned region embeddings to facilitate precise visual-language grounding. By harnessing Large Language Models (LLMs), PathFLIP can seamlessly follow diverse clinical instructions and adapt to varied diagnostic contexts. Furthermore, it exhibits versatile capabilities across multiple paradigms, efficiently handling slide-level classification and retrieval, fine-grained lesion localization, and instruction following. Extensive experiments demonstrate that PathFLIP outperforms existing large-scale pathological VLMs on four representative benchmarks while requiring significantly less training data, paving the way for fine-grained, instruction-aware WSI interpretation in clinical practice.

Fengchun Liu, Songhan Jiang, Linghan Cai +2

Harbin Institute of Technology, Shenzhen, School of Computer Science and Technology · National University of Singapore, Department of Electronic and Computer Engineering

Computational Pathology Vision-Language Grounding Medical VLMs Whole-Slide Image Analysis

Nov 7, 2025

Towards Cellular-Scale Interpretability in Pathology Foundation Models for Biomarker Assessment

Molecular biomarker testing in pathology is often costly and tissue-consuming, limiting scalable clinical deployment. Artificial intelligence applied to hematoxylin and eosin (HE)-stained histology could enable rapid biomarker screening, but clinical translation requires models that are both accurate and interpretable. Here we introduce Hireca, a biomarker-focused pathology foundation model pretrained on more than 80,000 whole-slide images spanning 38 organ types from three medical centers, together with CytoMap, an interpretability module that localizes cellular-scale evidence underlying predictions. Across 10 biomarker tasks encompassing morphological, molecular, genetic, and spatial-transcriptomic-proxy readouts, Hireca ranked first in five tasks and outperformed comparable models overall. In evaluation by eight pathologists from two countries, CytoMap was consistently preferred over alternative visualization approaches and revealed error patterns in difficult cases. These results position Hireca and CytoMap as a transparent framework for clinically reviewable biomarker assessment directly from routine HE histology.

Jingsong Liu, Han Li, Zhengyang Xu +19

Institute of Pathology, Technical University of Munich, Munich, Germany · Munich Center for Machine Learning (MCML), Munich, Germany · Munich Data Science Institute (MDSI), Munich, Germany +6

Computational Pathology Healthcare Pathology Foundation Models Explainable Medical Image Analysis Whole-Slide Image Analysis

Oct 7, 2025

Multimodal Feature Prototype Learning for Interpretable and Discriminative Cancer Survival Prediction

Survival analysis plays a vital role in making clinical decisions. However, the models currently in use are often difficult to interpret, which reduces their usefulness in clinical settings. Prototype learning presents a potential solution, yet traditional methods focus on local similarities and static matching, neglecting the broader tumor context and lacking strong semantic alignment with genomic data. To overcome these issues, we introduce an innovative prototype-based multimodal framework, FeatProto, aimed at enhancing cancer survival prediction by addressing significant limitations in current prototype learning methodologies within pathology. Our framework establishes a unified feature prototype space that integrates both global and local features of whole slide images (WSI) with genomic profiles. This integration facilitates traceable and interpretable decision-making processes. Our approach includes three main innovations: (1) A robust phenotype representation that merges critical patches with global context, harmonized with genomic data to minimize local bias. (2) An Exponential Prototype Update Strategy (EMA ProtoUp) that sustains stable cross-modal associations and employs a wandering mechanism to adapt prototypes flexibly to tumor heterogeneity. (3) A hierarchical prototype matching scheme designed to capture global centrality, local typicality, and cohort-level trends, thereby refining prototype inference. Comprehensive evaluations on four publicly available cancer datasets indicate that our method surpasses current leading unimodal and multimodal survival prediction techniques in both accuracy and interpretability, providing a new perspective on prototype learning for critical medical applications. Our source code is available at https://github.com/JSLiam94/FeatProto.

Shuo Jiang, Zhuwen Chen, Liaoman Xu +6

Hangzhou Dianzi University, Hangzhou 310018, China · School of Information and Communication Technology, Griffith University, QLD 4215, Australia · Shenzhen Research Institute of Big Data, Shenzhen 518172, China +3

Computational Pathology Cancer Survival Prediction Prototype Learning Multimodal Survival Analysis Explainable Medical Image Analysis Whole-Slide Image Analysis+1