Whole-Slide Image Analysis

Latest papers 133

Jun 30, 2026cs.CV

TaxoMIL: Taxonomy-Constrained Learning for Hierarchical Whole Slide Image Analysis

Whole slide image (WSI) analysis is central to computational pathology, with multiple instance learning (MIL) emerging as the standard pipeline for slide-level diagnosis. However, conventional approaches formulate WSI diagnosis as a flat classification task over discrete labels, contradicting the inherently hierarchical, coarse-to-fine nature of clinical reasoning. Although recent hierarchical classifiers and vision-language models (VLMs) have sought to address this structural gap, they either fail to capture semantic continuity between related diagnoses or suffer from unconstrained text generation that produces taxonomic hallucinations and parent-child label violations. To address these limitations, we propose TaxoMIL, a taxonomy-constrained framework that reformulates WSI diagnosis as a multi-granularity text generation task. TaxoMIL utilizes a dual-head Transformer decoder to generate coarse- and fine-level diagnostic text, and introduces taxonomy-guided objectives that explicitly structure the label embedding space and strictly ground slide-level visual representations within the clinical taxonomy. Extensive experiments across three diverse WSI datasets demonstrate that TaxoMIL consistently outperforms state-of-the-art MIL classifiers and VLM-based generative methods, yielding accurate and hierarchy-aware diagnostic predictions. The code is released at https://github.com/QuIIL/TaxoMIL
Jun 29, 2026cs.CV

A Multi Center Breast FNAC Whole-Slide Cytology Dataset for AI-Assisted Patch-Wise Classification Using C1 to C5 Reporting Categories

We present a multi center breast fine needle aspiration cytology (FNAC) dataset designed for patch wise classification using C1 to C5 reporting labels. The prospective dataset includes 321 patients and 470 whole-slide images (WSIs) collected from participating tertiary medical centers in India between May 2023 and March 2026. Slides were stained using Papanicolaou (190 WSIs) or MayGrunwald Giemsa (280 WSIs), scanned on a Hamamatsu NanoZoomer S360 at 40X magnification and 0.25 microns per pixel, and stored directly in NDPI format. Across the 470 WSIs, 446 WSIs contain annotated patch regions, yielding 7,398 PNG image patches with expert-verified C1 to C5 labels. The release includes NDPI WSIs, WSI-level GeoJSON annotation files, extracted patch images, deidentified metadata, a data dictionary, a validation summary, a manifest linking WSIs to Zenodo records, and code for dataset inspection and reuse. The complete dataset is approximately 950 GB and is available through Zenodo.
Jun 29, 2026cs.CV

Uncertainty Estimation in Pathology Foundation Models via Deep Mutual Learning

Pathology foundation models (PFMs) offer generalizable representations for whole-slide image (WSI) analysis, yet their clinical adoption remains limited. Specifically, their predictions lack reliable confidence estimates, and no single PFM is universally best across tasks, which severely undermines trust in medical settings. To overcome this, we propose DICE\mathtt{DICE}, a plug-and-play framework that ensembles KK frozen PFMs and models their disagreement as a proxy for uncertainty estimation. To ensure this proxy yields meaningful estimates, we align the ensemble members via deep mutual learning, and theoretically show that this objective upper-bounds the model uncertainty. Additionally, we demonstrate that the ensemble's consensus localizes abnormalities at the patch level without any explicit supervision. We evaluate DICE\mathtt{DICE} on three challenging WSI benchmarks. Notably, our framework provides reliable uncertainty estimates that accurately flag failure-prone cases under in- and out-of-distribution settings, while matching or outperforming SOTA baselines in classification, calibration, and localization. Overall, DICE\mathtt{DICE} takes a crucial step toward translating PFMs into uncertainty-aware decision-support systems.
Jun 29, 2026eess.IV

Data-Efficient Multimodal Alignment for Histopathology-based Molecular Prediction

H&E-stained whole-slide images offer cohort-scale availability and rich spatial context but lack molecular specificity, whereas bulk RNA-seq provides transcriptome-wide resolution at high cost with limited archival availability. We show that training a lightweight alignment module atop frozen histopathology and RNA-Seq foundation models enables open-vocabulary molecular prompting -- querying H&E slides with gene-set signatures to predict pathway activity without sequencing or end-to-end retraining. Using contrastive learning on a multi-cancer cohort (N=1,720), we achieve a 25-fold improvement in retrieval over baseline methods. Systematic analysis reveals a graduated predictability spectrum: morphologically grounded programs (cell-cycle programs, immune-related) are most reliably predicted (R^2>0.5), while predicting pathways with no morphological footprint remains challenging as expected. We validate clinical utility on the POSEIDON clinical trial: H&E-predicted squamous cell carcinoma scores recapitulate NSCLC subtype identity and predicted IFN-gamma mirror PD-L1 tumor-cell expression groups. Furthermore, genesets describing immune activation and fibrosis predict known tumor microenvironment archetypes from histology alone. We further validate generalization of our approach across unseen cohorts and demonstrate data-efficient domain adaptation, establishing a slide-native framework for molecular analysis on H&E images.
Jun 25, 2026cs.CV

Distribution-based deep multiple instance learning for tumor proportion scoring in NSCLC

Accurate assessment of tumor proportion score (TPS) in non-small cell lung cancer (NSCLC) is critical for treatment planning and prognosis. Key challenges include the tedious manual work required to annotate each slide, combined with the limited number of experts certified for this task. Multiple instance learning (MIL) has proven to be an effective approach for predicting TPS scores at the slide level; however, existing methods struggle with non-expressive (zero class) images. Our approach involves two models: (1) an embedding-extraction and multiclass-classification network that captures the histopathological features of individual patches, and (2) a MIL model that aggregates these embeddings to predict zero-inflated beta (ZIBeta) parameters representing the overall TPS probability distribution for the entire slide. Using only slide-level TPS scores as labels, we demonstrate how this end-to-end framework can leverage a novel distribution-based architecture to improve prediction accuracy and explainability. ZIBeta modeling significantly outperforms baseline linear and ridge regression while capturing expected accuracy through distribution concentration.
Jun 23, 2026cs.IR

Reducing Redundancy in Whole-Slide Image Patching for Scalable Indexing and Retrieval

The rapid growth of digital pathology has created an urgent need for efficient indexing and retrieval of whole slide images (WSIs). This need is intensified by emerging generative AI workflows, particularly retrieval-augmented generation (RAG), which require dependable similarity search to support high-stakes clinical decision-making. Yet the substantial cost of high-performance storage limits the scalability and accessibility of WSI indexing for many healthcare institutions. Consequently, methods that can reduce storage demands while preserving retrieval accuracy have become a critical research priority. We propose ARReST (Antithetical Redundancy Reduction Strategy), a principled oppositional framework that leverages redundancy across dissimilar tissue classes to markedly decrease the number of patches that must be indexed from each WSI. Instead of eliminating only within-class duplicates, ARReST identifies antithetical patches-those whose representations contribute minimally to cross-class discrimination-and prunes them from the searchable archive. This targeted reduction substantially compresses the index without sacrificing morphological diversity or retrieval fidelity. By minimizing superfluous patch representations, ARReST reduces storage footprint, lowers computational overhead, and accelerates similarity search across large pathology repositories. Extensive experiments on TCGA repository (The Cancer Genome Atlas with 21 organs) demonstrate that ARReST achieves significant index compression while maintaining competitive retrieval performance. The observed storage savings of 3% to 60% (14%±\pm13%) can be reliably achieved without compromising retrieval performance for many organs. The proposed strategy enables scalable, cost-efficient WSI indexing and is well-suited for next-generation retrieval-driven clinical AI systems.
Jun 19, 2026cs.CV

HERO: Hypothesis-Driven Evidence Retrieval from Omics for Multi-Task Breast Cancer Analysis

Matched multi-omics can improve WSI-based biomarker and prognosis prediction, but most existing pipelines use omics as a paral lel feature stream or textual context rather than as an explicit retrieval constraint. HERO asks whether observed omics can be a testable mor phology hypothesis: a sparse pathway-to-morphology prior maps DNA methylation and miRNA into a K-dimensional intent vector m (K=16), TF-IDF retrieval over structured 10 captions selects endpoint-relevant regions, and a cosine gate c=cos(m,v) triggers deterministic deficit driven repair when c<τc. This closed-loop design bounds VLM calls, reduces reliance on embedding-based semantic matching, and makes every retrieval and verification step lexically auditable. On TCGA-BRCA (930WSIs, patient-level 5-fold CV), HERO sets new state-of-the-art across ER, PR, HER2, subtype, and risk prediction, outperforming both multimodal fusion and VLM-based baselines.
Jun 19, 2026cs.CV

Contrastive and Adaptive Multi-modal Masked Autoencoder for Spatial Transcriptomics

The high cost of spatial transcriptomics (ST) has driven extensive studies into predicting gene expression directly from H&E histology images. However, this prediction task faces an inherent limitation, as tissue morphology alone provides insufficient information to fully resolve underlying gene expression. To address this limitation, a recent study leverages partial gene expression to guide the prediction process alongside histology images. Building on this paradigm, we approach the prediction task as a spatial imputation problem, employing a Masked Autoencoder (MAE) to utilize a small fraction of gene expression as genetic anchors for inferring whole-slide gene expression profiles. Specifically, we propose a bio-saliency score and a learning-to-rank strategy to adaptively identify the most informative spots within the tissue. Based on these identified spots, our framework selects contiguous regions as genetic anchors to ensure suitability for real-world ST profiling hardware. To effectively leverage these anchors, we design a cross-modal joint encoder that integrates visual and genetic modalities. By aligning the selected anchors with their corresponding visual features via contrastive learning, the encoder generates robust joint representations to accurately predict gene expression across the whole slide. Notably, our framework consistently surpasses existing methods in both histology-only prediction and spatial imputation, achieving superior accuracy even without genetic anchors and further excelling with as little as 10% transcriptomic coverage. Our code is available at https://github.com/Kyyle2114/CAMMST.
Jun 18, 2026cs.CV

Semantic-Anchored Evidential Fusion for Domain-Robust Whole-Slide Survival Analysis

Whole-slide images (WSIs) are widely used for computational cancer prognosis. However, most existing methods primarily focus on in-domain performance and fail to generalize across clinical centers. This limitation stems from their reliance on pixel-derived representations that are highly susceptible to domain-specific artifacts caused by staining protocols and scanner hardware. We hypothesize that high-level pathology semantics, such as tumor grade and micro-environmental architecture, provide a domain-invariant semantic representation that mirrors the robust diagnostic logic of human pathologists. Therefore, we propose a Semantic-Anchored Evidential Fusion Survival (SAEFS) framework, where SAEFS derives semantic anchors from WSIs via Visual Question Answering (VQA), employs a dual-stream WSI evidence extraction architecture, uses Dirichlet-based Subjective Logic to model uncertainty, and fuses semantic and visual evidence through a cautious conjunction rule to avoid overconfident fusion from correlated sources. Trained exclusively on one source domain and evaluated zero-shot across four unseen domains, SAEFS consistently outperforms state-of-the-art models both in prediction accuracy and reliability, improving the average C-index by 10.2%. Quantitative analyses further show that VQA-derived semantic features exhibit significantly lower cross-center divergence than pixel-derived features, highlighting their robustness for cross-center clinical applications.
Jun 16, 2026cs.CV

Predicting Immune Biomarkers with MultiModal Mixture-of-Expert Pathology Foundation Models Empowers Precision Oncology

Predicting immune biomarkers associated with the tumor immune microenvironment (TIME) is critical for advancing precision oncology, yet existing approaches are largely limited to single image modalities and suffer from insufficient resolution and incomplete utilization of complementary clinical and biological information. Here we introduce MixTIME, a multimodal foundation model that leverages a mixture-of-experts (MoE) architecture to integrate pathology foundation models trained across distinct modalities: image only (UNIv2), image text (CONCHv1.5), and image transcriptomic (STPath) representations for pixel-level and slide-level prediction of multiplex immunofluorescence (mIF) protein expression from hematoxylin and eosin (HE) whole-slide images. MixTIME employs a learnable router to dynamically weight expert contributions and is trained with a distribution- and tendency-aware loss function. Benchmarked on two datasets of different scales, MixTIME achieves state-of-the-art performance across 17 protein markers as measured by correlation metrics. The predicted mIF profiles substantially enhance downstream tasks, including spatial domain identification, survival prediction, and AI-assisted pathology report generation validated by expert pathologists from multiple institutes across the world. Furthermore, MixTIME enables longitudinal tracking of protein expression dynamics across clinical time points and reveals protein gene interaction patterns linked to drug resistance and immune suppression in tumor microenvironments. Collectively, MixTIME provides a scalable framework for multimodal biomarker discovery and clinical translation in computational pathology.
Jun 15, 2026cs.CV

Vision-Language Models as Zero-Annotation Oracles in Histopathology

Foreground segmentation is the critical first step of every computational pathology pipeline, yet existing methods rely on hand-tuned heuristics or supervised models that overfit to narrow stain and scanner distributions, failing silently on specialised stains such as Jones silver or Elastica van Gieson. We propose a coarse-to-fine approach that recasts foreground segmentation as a visual perception task and leverages general-purpose vision-language models (VLMs) as zero-annotation oracles. Our key insight is that tissue-versus-background discrimination is a natural-image recognition problem, not a histopathological one, so VLMs trained on internet-scale corpora generalise where domain-specific models cannot. We introduce Leica-75, a benchmark of 75 renal transplant whole-slide images spanning three stain families. On Leica-75, our method achieves the highest segmentation quality on out-of-distribution stains (Dice 0.858 +/- 0.027 on Jones, 0.853 +/- 0.041 on EVG) with 7x lower cross-stain variance than the best supervised baseline, while remaining competitive on in-distribution H&E. Few-shot prompting with automatically curated exemplars (Auto-context) rescues hard cases on Stress-32 (n=32), a curated stress-test subset (Dice 0.470 to 0.819 for the 2B model). VLM-based annotation review matches human expert consensus (kappa=0.989 for blur detection; mean precision/recall grading accuracy 0.708 vs. human 0.646 for segmentation mask review). The resulting pseudo-labels are used to distil lightweight student models that are as performant as the teacher model while running for a fraction of the cost. Our framework provides a principled, scalable solution to a persistent infrastructure bottleneck in digital pathology.
Jun 14, 2026cs.CV

RaLMPH: Reliability-aware Learning for Multi-Pathologist Harmonization in Whole-Slide Image Classification

Multiple Instance Learning (MIL) is a standard paradigm for Whole-Slide Image (WSI) analysis and has achieved strong results in computational pathology. However, most MIL pipelines assume a single "gold" label per slide, which conflicts with clinical practice where substantial inter-pathologist variability is common. Existing multi-annotator learning and label-refinement methods typically estimate global annotator reliability or rely on single-instance assumptions, making them poorly suited to MIL and to localized diagnostic contexts where experts disagree. We propose RaLMPH (Reliability-aware Learning for Multi-Pathologist Harmonization), a MIL-based label reconciliation framework for WSIs annotated by multiple pathologists. RaLMPH introduces a reliability field that jointly models (i) local neighborhood structure in WSI feature space and (ii) expert uncertainty (entropy), enabling per-sample identification of trustworthy reference neighborhoods. Leveraging this field, RaLMPH performs sample-wise local annotator ranking to select reliable opinions per slide and applies an adaptive gating mechanism to fuse labels conditioned on local reliability. Experiments on a clinical WSI dataset with labels from six pathologists, as well as controlled simulated benchmarks, show that RaLMPH consistently outperforms existing approaches. Further analyses clarify how our reliability-aware mechanism improves label reconciliation and downstream MIL performance.
Jun 10, 2026cs.CV

How Seemingly Inconsequential Design Choices Dictate Performance of LLMs in Pathology

General-purpose large language models (LLMs) are routinely used as baselines when evaluating specialized pathology models on whole-slide images (WSIs). Because WSIs exceed contemporary model context limits, LLM baselines routinely use small, high-magnification patches processed independently via majority voting, without systematic evaluation of seemingly inconsequential design choices such as patch size, patch count, and magnification. Generalist LLMs have consistently underperformed specialized systems, reinforcing the perception that domain-specific training or architectural adaptation is necessary for pathology tasks involving WSIs. Here, we conduct a systematic factorial analysis of four input design factors: inference mode, patch size, magnification, and patch count. We demonstrate that prior studies have overstated the gap between specialized models and general-purpose LLMs by choosing non-optimized input configurations. On the MultiPathQA benchmark, switching to a single balanced configuration (large patches at lower magnification, processed jointly) raises GPT-5 from 15.1% to 39.5% on cancer-type classification (TCGA) and from 38.1% to 62.9% on organ classification (GTEx). Per-task optimization yields further gains up to 43.9% (TCGA) and 71.6% (GTEx). The same configuration generalizes to two other models and to a fully held-out CPTAC cohort, where it improves Gemini 3 Flash by 23.4 percentage points without any task-specific tuning.
Jun 10, 2026cs.CV

Atlas H&E-TME: Scalable AI-Based Tissue Profiling at Expert Pathologist-Level Accuracy

Hematoxylin and eosin (H&E) staining is the cornerstone of histopathology, yet scalable, quantitative analysis of H&E whole-slide images (WSIs) remains a central challenge in computational pathology. We present Atlas H&E-TME, an AI-based system built on the Atlas family of pathology foundation models that predicts tissue quality, tissue region, and cell type labels across multiple cancer types, yielding over 4,500 quantitative readouts per slide at cell-level resolution. A key challenge to validating such systems is overcoming morphological ambiguity inherent to H&E-only ground truth and the limited scalability of more informed references drawing on modalities such as immunohistochemistry (IHC). We address this with a dual validation framework combining biologically grounded depth with technical and morphological breadth. For depth, we propose an IHC-informed multi-pathologist consensus protocol that substantially improves inter-rater agreement over conventional H&E-only annotation. This yields a molecularly grounded reference against which we compare Atlas H&E-TME and pathologists working from H&E alone. For breadth, we benchmark Atlas H&E-TME on over 200,000 high-confidence H&E-only pathologist annotations across 1,500+ cases spanning eight cancer types and their most common metastatic sites, with subtypes covering >90% of clinical cases per cancer type, drawn from 25+ sources and 8+ scanner models. Benchmarked against the IHC-informed consensus, Atlas H&E-TME matches or exceeds pathologist H&E-only performance and generalizes consistently and robustly across this broad morphological and technical scope. In doing so, Atlas H&E-TME turns the H&E slide -- the most ubiquitous data in pathology -- into a scalable, quantitative window into the tumor and its microenvironment, laying a foundation for the next generation of tissue-based biomarkers in translational and clinical research.
Jun 10, 2026cs.CV

AGE-MIL: Anchor-Guided Evidence Learning for Patient-Level Prediction

Existing computational pathology methods predominantly operate within whole-slide image (WSI)-level multiple instance learning (MIL) paradigms, while patient-level modeling remains underexplored. In routine pathological practice, however, pathologists derive diagnostic and prognostic conclusions by integrating evidence across multiple WSIs rather than relying on any single slide. This discrepancy creates a fundamental misalignment when patient-level supervision is directly imposed on conventional MIL frameworks, often leading to unstable optimization and degraded predictive reliability. To address this issue, we propose Anchor-Guided Evidence MIL (AGE-MIL), a weakly supervised framework for patient-level prediction. AGE-MIL constructs a patient-level anchor from slide representations to capture global pathological context and guide the retrieval and integration of diagnostically relevant local patches, enabling robust patient-level modeling. Patient-level risk is further modeled as an evidence accumulation process, promoting stable optimization under weak supervision. AGE-MIL is evaluated on six clinically relevant patient-level prediction tasks from two independent cohorts. Experimental results show that the proposed framework consistently outperforms eight state-of-the-art MIL methods. Code is available at https://github.com/wodeniua/AGE-MIL.
Jun 10, 2026cs.CV

SheafStain: Sheaf-Theoretic Schrödinger Bridge for Spatially and Biologically Coherent Virtual Staining

Current virtual staining approaches offer the potential for time- and cost-efficient biomarker quantification in cancer diagnostics and prognostics. However, patch-wise inference for gigapixel whole-slide images (WSIs) fails to maintain spatial continuity, yielding artifacts that cause catastrophic mismatches with ground-truth images. Although pathology Vision Foundation Models (VFMs) offer rich representations, their self-attention causes varying global contexts to produce inconsistent embeddings for the same physical region. We formalize and validate this ``context contamination'' as a sheaf-theoretic problem where these embeddings form a presheaf whose sections disagree on overlaps, so no global section restricts to them. To address this, we propose SheafStain, a new approach that reinterprets VFM features as sheaf-like sections for spatially and biologically coherent virtual staining. Specifically, SheafStain integrates class and patch tokens into a Schrödinger Bridge framework as sheaf-like sections. While the class token anchors biological consistency, patch tokens form a per-position spatial map. An encoder co-pretrained on Hematoxylin & Eosin (H&E) and Immunohistochemistry (IHC) yields cross-stain sections, so a single VFM feature space supervises both input conditioning and output stain alignment. Departing from prior work that evaluates on isolated 256×256256 \times 256 patches and either random-crops or resizes the 1024×10241024 \times 1024 ground truth, we translate at 256×256256 \times 256 and evaluate on the stitched 1024×10241024 \times 1024 outputs across HER2, ER, PR, and Ki-67. SheafStain demonstrates promising results against six prior methods while mitigating patch-boundary stitching artifacts. Code is available at https://github.com/deepnoid-ai/SheafStain.
Jun 9, 2026cs.CV

From Patches to Patients: A study of the tile-to-slide performance transferability in Digital Pathology

Foundation Models (FMs) have recently redefined the state-of-the-art in histopathology by providing robust representations for whole-slide image (WSI) analysis. However, selecting the optimal foundation model (FM) for a specific clinical cohort currently requires multiple preprocessing steps, followed by computationally expensive feature extraction and the training of a Multiple Instance Learning (MIL) aggregator for every model. In this work, we investigate whether efficient tile-level linear probing can serve as a reliable proxy for slide-level performance, reducing the need to run full slide-level pipelines for every candidate encoder. We benchmark 19 state-of-the-art FMs on 42 slide-level and 16 tile-level tasks, comparing tile probing metrics against slide-level outcomes using ABMIL and Mean Pooling aggregations. We observe a high correlation between tile and slide performance across varying task difficulties, indicating that encoder representation quality is the primary determinant of WSI success. Sensitivity analyses show that transferability is stable across models and is more influenced by cohort sizes and numbers of tiles per slide than by average task difficulty. We also measure the agreement in best performing models between tile and slide-level tasks, showing tile benchmarks reliably shortlist strong candidates. Overall, our study indicates that tile-level benchmarking provides an efficient and practical first step for narrowing down candidate models, while slide-level evaluation remains essential for final validation on clinical tasks.
Jun 8, 2026cs.CV

GD-MIL: Grade-Disentangled Multiple Instance Learning for Multimodal Biochemical Recurrence Prediction in Prostate Cancer

Biochemical recurrence (BCR) after radical prostatectomy is a critical endpoint in prostate cancer, yet risk stratification relies almost entirely on variables dominated by Gleason grade. Whether H&E whole slide images (WSIs) carry prognostic signal beyond grade, and whether multiple instance learning (MIL) can recover it, remains unsettled. A key obstacle is that many pipelines select model checkpoints on the evaluation fold, artificially inflating concordance. We construct a rigorous benchmark on TCGA-PRAD (487 patients, 101 BCR events) using strict out-of-fold scoring over five-fold cross-validation repeated across five seeds. The choice of MIL aggregator (ABMIL, CLAM, TransMIL, PatchGCN) has little effect (C-index 0.61-0.64 with UNI2-h), while the feature extractor is the dominant factor (ResNet50 0.566 versus pathology foundation models up to 0.639). A clinical Cox model on grade, stage, and age reaches 0.687; no imaging-only model significantly outperforms it (p > 0.10). We introduce Grade-Disentangled MIL (GD-MIL), a gated-attention MIL encoder trained with a gradient-reversal grade adversary that encourages the slide representation to be invariant to Gleason grade before late fusion with clinical variables. GD-MIL achieves C-index 0.704, significantly outperforming both the clinical baseline (delta-c = +0.029, p = 0.0005) and the best imaging-only model (delta-c = +0.062, p = 0.039), suggesting H&E morphology contains prognostic information complementary to grade. A median risk split yields log-rank p < 0.0001 separation in BCR-free survival (~20% vs ~70% at five years).
Jun 7, 2026cs.CV

Learnable Token Sparsification for Efficient Gigapixel Whole Slide Image Reasoning

The processing of gigapixel whole slide images within vision language models faces a major difficulty due to an excessive number of visual tokens. Existing solutions typically rely on spatial downsampling or heuristic pruning strategies that operate without training, and these methods often discard subtle but clinically meaningful patterns because pathological evidence is scattered irregularly across the tissue. To overcome this limitation, we reformulate token reduction in whole slide images as a trainable sparsification problem, allowing the model to learn an optimal selection strategy instead of following fixed heuristics. We propose a decoupled routing architecture. To enable gradient propagation through the nondifferentiable pruning operation during training, we introduce a component called SparseLearn. This component uses a variance-preserving noise gate that regulates the information flow of each patch via a differentiable Soft Top-K operator, together with a diagonal attention denoiser that recovers perturbed representations without leaking spatial information. At inference time, the SparseLearn module is entirely discarded, and the trained scorer applies a deterministic Hard Top-K operator to keep only the highest scoring 32 tokens, incurring no extra computation. By compressing the visual sequence down to a sparse set of just 32 tokens, which represents as little as 0.78% of the original length, our framework achieves 73.32% overall accuracy on SlideBench (TCGA), consistently surpassing sampling-based baselines and general-purpose vision language models. It also demonstrates strong zero shot generalization on SlideBench (BCNB) and WSI VQA*. By resolving the visual context bottleneck and preventing the dilution of sparse diagnostic evidence, this work provides a highly efficient paradigm for end to end gigapixel whole slide image reasoning.
Jun 6, 2026cs.AI

A Multi-modal Agentic Co-pilot for Evidence Grounded Computational Pathology

Pathology is the cornerstone of modern medicine, where accurate decision-making relies heavily on evidence-based practices. While artificial intelligence (AI) has the potential to transform clinical workflows, the intersection of AI and evidence-based medicine remains under-explored, with primitive attempts restricted to text-only general medicine. In this work, we present PathPocket, a multimodal AI agentic co-pilot designed specifically for evidence grounded pathology. We construct the most comprehensive pathology evidence corpus to date, encompassing approximately 110,472 public and authorized documents structured across a rigorous hierarchy of evidence from clinical guideline to expert opinion. From this meticulously graded foundation, we build a large-scale multimodal pathology hypergraph containing over 4.55 million entities and 7.10 million relations. Serving as a robust knowledge engine, this hypergraph provides traceable evidence for a collaborative multi-agent reasoning framework integrating input understanding, evidence retrieval, filtering, and diagnosis generation. This enables PathPocket to seamlessly resolve a wide spectrum of clinical tasks, ranging from text-only queries to complex multimodal diagnostics involving region-of-interest (ROI) and gigapixel whole-slide images (WSIs). We rigorously evaluate the system on a multidimensional benchmark of over 200,000 real-world cases, where it significantly outperforms existing state-of-the-arts. Crucially, extensive user studies demonstrate that PathPocket substantially improves the diagnostic accuracy and confidence of pathologists. By directly grounding pathology interpretations in verifiable literature, PathPocket offers a practical and scalable solution for the future of evidence grounded computational pathology.
Jun 5, 2026cs.CV

Mitosis Detection in the Wild: Multi-Tumor and Context-Aware Generalization in the MIDOG 2025 Challenge

Automated mitosis detection is a well-established task in computational pathology. While previous benchmarks focused on scanner-induced domain shift, clinical "real-world" application requires models to be robust across the vast variance to be expected in the histological landscape. The MItosis DOmain Generalization (MIDOG) 2025 challenge was designed to evaluate algorithmic performance across unprecedented biological and contextual diversity. We curated a test dataset of 365 cases, encompassing 12 distinct human, canine and feline tumor types, digitized across multiple scanning platforms. Moving beyond hand-selected hotspots, the challenge required detection also in random tissue areas (representative of the whole slide detection situation) and challenging areas (areas rich in hard negatives). In the second track, we introduced the classification of atypical mitotic figures (AMFs). There were 18 teams submitting to the detection track, with F1 scores ranging up to 0.740. In the AMF detection track, we had 21 submissions with balanced accuracy values up to 0.908. Our analysis reveals that while most models perform reliably in traditional hotspots, significant performance degradation occurs in challenging ROIs, where false positive rates tripled. Furthermore, performance varied significantly across the 12 tumor types, highlighting "blind spots" in current state-of-the-art architectures when encountering rare or highly pleomorphic malignancies. Moreover, we evaluated the effectiveness of ensembling and found a mean increases of 1.5 and 1.3 percentage points in F1 score and balanced accuracy, respectively. In contrast, TTA showed no relevant improvement. MIDOG 2025 demonstrates that "in the wild" mitosis detection remains a significant hurdle. The transition from hotspot-only evaluation to a multi-contextual framework provides a more realistic proxy for clinical reliability.
Jun 5, 2026eess.IV

DaX: Learning General Pathology Representations Across Scales

Computational pathology requires visual representations that transfer across diverse clinical endpoints and remain robust to variation in magnification, staining, scanner type, slide preparation, and input resolution. We present DaX, a pathology vision foundation model that adapts DINOv3-style self-supervised learning to whole-slide histopathology. DaX is initialized from natural-image DINOv3 weights and incorporates continuous magnification training, cross-scale tissue views, orientation-agnostic and acquisition-robust augmentation, multi-input-size training, and Gram-anchored dense consistency. These designs aim to connect local cellular morphology with global tissue architecture while stabilizing dense token-level representations across input scales. We further construct a WSI-level benchmark comprising 161 clinically meaningful tasks from 44 public datasets, covering 28,182 patients and 34,394 slides across four clinical domains and nine task categories. All models are evaluated under a fixed patient-level cross-validation protocol with fold-level statistical ranking, enabling reproducible comparisons that are less sensitive to split-dependent variation. Across this benchmark, DaX achieves the highest mean performance across tasks and consistently strong task-level ranking scores, with gains spanning diagnostic pathology, biomarker and molecular profiling, tissue/specimen context, and risk, response, and prognosis. These results support DaX as a transferable visual encoder for computational pathology and provide a standardized evaluation framework for future pathology foundation models. Project page: https://alibaba-damo-academy.github.io/DaX/benchboard/.
Jun 5, 2026cs.CV

LRMIL: Efficient Low-Resolution Multiple Instance Learning via High-Resolution Knowledge Distillation for Whole Slide Image Classification

Multiple instance learning (MIL) has become a standard paradigm for whole slide image (WSI) analysis in digital pathology, as it enables slide-level prediction without dense annotations. Existing MIL methods typically rely on exhaustive extraction and encoding of high-resolution patches. However, this practice suffers from two critical limitations in real-world clinical settings: it struggles to capture global visual cues at lower magnifications, and incurs substantial computational overhead due to the massive number of high-resolution patches per slide. To address these limitations, we propose an efficient low-resolution multiple instance learning (LRMIL) framework that transfers high-resolution knowledge to low-resolution representations. LRMIL adopts a two-stage distillation strategy. First, patch-level cross-resolution distillation aligns low-resolution patch embeddings with high-resolution representations. Second, slide-level knowledge distillation trains a low-resolution student MIL model under both slide-level supervision and teacher guidance. At inference time, LRMIL operates exclusively on low-resolution patches, substantially reducing data preprocessing and computational cost. Extensive experiments on multiple WSI benchmarks demonstrate that LRMIL consistently outperforms state-of-the-art MIL methods while achieving more efficient inference. These results highlight LRMIL as a practical and scalable solution for WSI analysis in clinical pathology.
Jun 1, 2026cs.CV

Pathway-Structured Privileged Distillation for Deployable Computational Pathology

Integrating transcriptomics and histopathology can improve cancer risk modelling, yet practical use is constrained by the limited availability of RNA profiling in routine settings. Here we introduce Mixture of Pathway Experts (MoPE), a knowledge-distillation framework that reframes multimodal learning as privileged distillation for histology-only inference. MoPE is motivated by the partial observability between RNA profiles and whole-slide images: histology can capture morphology-linked consequences of certain molecular programmes, but cannot be expected to reconstruct the full transcriptomic state. MoPE encodes RNA-derived pathways and transfers the molecular supervision to pathway-indexed pathology experts through memory-usage alignment. Across diverse public benchmarks and two independent breast cancer cohorts, MoPE consistently improved WSI-only inference performance relative to baseline methods. Pathway-usage analyses and human-audited visual inspection provide bounded inspection of model behaviour and candidate morphology-linked readouts. These results support pathway-structured privileged distillation as a promising route to using molecular information during training while preserving RNA-free inference.
Jun 1, 2026cs.CV

Deep Learning for Generating Computational PIN-4 Immunohistochemistry Staining from Prostate Biopsy H&E Images

Immunohistochemistry (IHC)is frequently used to resolve diagnostically ambiguous prostate cancer biopsy findings on hematoxylin and eosin (H&E)-stained tissue. However, PIN-4 IHC staining is typically performed on adjacent tissue sections, limiting direct spatial comparison between the H&E morphology and the corresponding immunophenotypic signal. A paired, registered H&E/PIN-4 dataset was constructed from routine clinical prostate biopsy whole-slide images (WSIs), and a conditional generative adversarial network (cGAN) was trained to synthesize PIN-4 staining patterns directly from native H&E image patches. The final dataset comprised 172 paired WSIs from 93 patients and 27,298 registered 1024x1024 patch pairs, spanning adenocarcinoma-positive and benign cases with representation across age, race, and ethnicity groups. The model was evaluated on a held-out test set of 1,814 patch pairs from 17 WSIs, achieving a mean peak signal-to-noise ratio (PSNR) of 21.88 dB, structural similarity index measure (SSIM) of 0.667, Pearson correlation coefficient (PCC) of 0.684, and learned perceptual image patch similarity (LPIPS) of 0.417. Qualitative review by a board-certified pathologist showed that generated images captured diagnostically relevant PIN-4 staining patterns, including AMACR/racemase expression and basal-cell-associated staining, while preserving spatial correspondence with the source H&E morphology. Accuracy of synthesis varied across morphologically complex regions, including high-grade carcinoma and intraductal carcinoma. These results support the feasibility of supervised PIN-4 synthesis from routinely acquired brightfield H&E prostate biopsy images. The approach enables direct interpretation of predicted PIN-4 marker patterns in the context of the source prostate H&E architecture, addressing a current spatial limitation of conventional adjacent-section IHC.
May 29, 2026cs.CV

Simple Token-Efficient Vision-Language Model for Case-level Pathology Synoptic Report Generation

Generating clinically useful pathology reports for pathology cases from whole-slide images (WSIs) is challenging due to gigapixel resolution, long visual-token sequences, and the complexity of case-level reasoning, where a single case may contain multiple WSIs with heterogeneous tissues and ambiguous findings. We present a simple token-efficient vision--language model for case-level synoptic report generation that remains practical under constrained GPU memory. Our architecture follows a minimal three-component design: a frozen pathology patch encoder, a lightweight two-layer MLP vision-language aligner, and a large language model decoder, with an explicit WSI marker token to separate slides within a case. Training proceeds in two supervised stages: (1) aligner-only WSI captioning using heterogeneous WSI-text pairs, and (2) case-level supervised fine-tuning on case-report pairs for structured report generation. To reduce sequence length, we represent each slide using 512×512512 \times 512 patches at 5×5\times magnification, which reduces the average sequence length by up to 64×64\times times compared to the commonly used 20×20\times patches. Combined with efficient training techniques, we enable practical training with only half a NVIDIA H100 GPU. Across both training stages, our approach achieves high ROUGE-L/METEOR/BLEU-4 scores while being substantially more efficient in memory and runtime. In AI-based evaluations, our model is consistently preferred over strong baselines. Extensive ablations characterize performance-efficiency trade-offs and identify simple choices that improve robustness in multi-WSI settings. Overall, this work provides a strong, reproducible baseline for efficient pathology report generation, lowering the barrier to multi-WSI VLM research under limited compute.
May 28, 2026cs.CV

SlideCheck: Guiding Self-Supervised Pretraining of Pathology Foundation Models via Dataset Distributions

Pathology foundation models are pretrained on large streams of WSI-derived patches, while supervision during data construction is often slide-level, sparse, or heterogeneous. This mismatch makes it difficult to understand and control which biological patterns enter the pretraining data. We propose SlideCheck, a lightweight pretraining data guidance tool built on frozen pathology foundation model patch features. Rather than serving as a standalone patch diagnostic model, SlideCheck provides explicit abnormality and malignancy scores for organizing, filtering, and auditing pathology pretraining data. SlideCheck uses a dual-head MLP to separately model broad abnormal morphology and malignant evidence. A regularized feature-space scorer provides a supervised anchor for patch-level evidence estimation, while score-attention agreement combines patch scores with WSI-level MIL attention to mine high-confidence pseudo labels. The same scores are then used to construct broad-positive ViT pretraining subsets, where a patch is selected if either abnormality or malignancy evidence exceeds a threshold. Experiments show that SlideCheck-defined data distributions influence the downstream behavior of self-supervised ViT pretraining, indicating that biological composition is an important controllable factor in pathology foundation model development. Curated subsets can approach full-data performance, suggesting that explicitly scored patch pools may support more efficient and auditable pretraining data construction. These findings position SlideCheck as a data guidance and auditing layer for transforming large, undifferentiated patch pools into controllable and reusable pretraining datasets.
May 25, 2026eess.IV

A Clinically Validated Foundation Model for Comprehensive Lung Pathology Interpretation

Pathological assessment guides lung cancer diagnosis, treatment selection, and prognostic evaluation, yet current CPath approaches rely on task-specific models for isolated objectives. Although pan-cancer foundation models offer versatility, they lack subspecialty-level depth and have not been evaluated across clinical workflows or prospectively validated in real-world settings. We introduce PulmoFoundation, a multi-center, prospectively validated, randomized controlled trial (RCT)-evaluated foundation model for comprehensive lung pathology assessment across pre-operative, intra-operative, and post-operative care. Built upon Virchow2 via subspecialty-specific pretraining using ~40,000 diagnostic H&E-stained whole-slide images (WSIs), PulmoFoundation was systematically evaluated on ~26,000 WSIs across 32 clinically relevant tasks. In addition to accurately predicting molecular markers and patient survival, our model achieves clinical-grade performance in core diagnostic tasks across biopsy, frozen section, and surgical resection slides. In a registered prospective study of 1,357 patients across 11 diagnostic tasks, our model achieved an average AUC of 92.3%. Using pre-specified triage thresholds, PulmoFoundation could reduce additional second-review burden for 68.8% of biopsies and 83.0% of frozen sections, and defer 44.5% of IHC stain orders, with PPVs of 1.0, 0.991, and 0.966. Beyond prospective validation, we conducted a crossover RCT with eight pathologists, in which AI assistance improved diagnostic accuracy across 4,928 case-reader pairs (91.7% w/ AI vs. 83.8% w/o AI). AI assistance also reduced median diagnostic time by 19.6%, increased diagnostic confidence by 8.7%, and improved inter-rater agreement from moderate (kappa = 0.56) to substantial (kappa = 0.76). Together, these evaluations support PulmoFoundation as a clinically validated decision-support system for lung pathology.
May 25, 2026cs.CV

Benchmarking Pathology Foundation Models for Spatial Domain Understanding

Pathology foundation models (PFMs) have emerged as a core approach for learning transferable representations from whole slide images (WSIs), and they are typically benchmarked through downstream clinical endpoints. While such task level evaluations are indispensable, they offer limited insight into what the representations themselves encode, particularly whether PFM embeddings can distinguish meaningful tissue regions and capture their spatial relationships. We present SpaPath-Bench, a representation level benchmark designed to diagnose spatial representation capability in PFMs. SpaPath-Bench formulates spatial domain identification (SDI) on paired whole slide image and spatial transcriptomics (ST) data as a diagnostic task. It curates 42 public paired WSI and ST slides, enables large scale evaluation across 19 encoders and seven SDI methods, and measures partition quality using three complementary criteria: unsupervised spatial coherence, transcriptomics referenced agreement, and expert referenced agreement. Across 83K runs, SpaPath-Bench reveals that different pretraining paradigms capture distinct aspects of tissue spatial architecture, and it provides practical guidance for building the next generation of spatially aware computational pathology models. Code and data pipelines are publicly available at https://bokai-zhao.github.io/SpaPath-benchboard/.
May 24, 2026cs.CV

Aligning Cellular Sheaves with Classifier Attention for Interpretable Weakly-Supervised Pathology Localization

Weakly-supervised classification of whole-slide images with attention-based multiple instance learning (ABMIL) on top of foundation features now reaches near-saturation on Camelyon16 slide-level performance, but the corresponding attention maps are an imperfect localization signal: in clinical interpretation, a model that classifies correctly without firing on the actual lesion is hard to trust. We address this gap with cellular sheaves, which equip each vertex and edge of a graph with a finite-dimensional vector space and consistent linear maps between them, providing a principled way to detect local disagreement on graph-structured data. We apply cellular sheaves to weakly-supervised tumour localization on whole-slide images, combining a sheaf disagreement field with ABMIL. The natural training objective, encouraging consistency between similar features, produces a disagreement field that tracks tissue-level texture rather than diagnostic content. We propose attention-conditional consistency, which uses the classifier's attention to define which neighbouring patches should agree. Joint training of the classifier and the sheaf under this objective produces a disagreement field with patch-level AUC 0.940 on Camelyon16 and raises the attention head from its ABMIL-alone level of 0.717 to 0.953. Two-stage ablation with the classifier frozen at its ABMIL values reaches only 0.727 on the disagreement field and leaves attention at 0.717, confirming that the gain comes from the projector co-adapting under both objectives, not from the loss change in isolation. The trained model transfers without retraining to annotated slides from Camelyon17, maintaining Delta AUC 0.932 +/- 0.083 and attention AUC 0.955 +/- 0.099. The result is an attention map and a sheaf-disagreement map that fire on the same diagnostic regions, giving clinicians two complementary explanations for each slide-level prediction.