Whole-Slide Image Analysis

Latest papers 133

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.
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.
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
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 0.9740.974 with H-Optimus-1, approaching the 0.9870.987 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.
Aug 4, 2026cs.CV

S3^3-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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.