Pathology Foundation Models

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9 papers in the last four weeks, down 18% on the four weeks before. 0.1% of all new papers.

Jul 13, 2026

LaGuadia: Language-Guided Adaptive Distillation from Pathology Foundation Models

Pathology Foundation Models (PFMs) offer powerful Whole Slide Image (WSI) representations but suffer from massive computational costs. While Knowledge Distillation (KD) can create efficient student models, existing multi-teacher methods often use suboptimal uniform weighting that ignores tissue heterogeneity. We propose LaGuadia (Language-Guided Adaptive DistillAtion), a framework that develops a compact pathology image encoder by dynamically integrating expertise from multiple PFMs under clinical linguistic guidance. Our approach utilizes a multi-stage pipeline: first, extracting visually observable clinical keywords from pathology reports; second, aligning visual features with these keywords via a Vision-Language meta-teacher (MedSigLIP) to provide dense semantic guidance; and finally, performing adaptive KD where teacher contributions are weighted based on their semantic alignment with the clinical narrative. Experiments on WSI captioning, visual question answering, and slide-level classification tasks demonstrate that an 87M parameter LaGuadia student model matches or exceeds foundation-scale models such as GigaPath and UNI, achieving strong factual consistency and robust generalization. These results highlight clinical language as an effective semantic anchor for building efficient and reliable digital pathology systems. Code is available at https://github.com/hvcl/LaGuadia.

Gangsu Kim, Won-Ki Jeong

Department of Computer Science and Engineering, College of Informatics, Korea University, Republic of Korea

Computational Pathology Pathology Foundation Models Medical VLMs Multimodal Foundation Models Knowledge Distillation

Jul 10, 2026

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

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

Jiawen Li, Tian Guan, Huijuan Shi +5

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

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

Jul 6, 2026

Multi-Teacher Contrastive Distillation for Edge-Efficient Pathology Foundation Models

Computational pathology foundation models (PFMs) have advanced whole-slide image analysis. However, their size and inference cost hinder local deployment in pathology departments. We propose MuCoDi, a pretraining framework that distills frozen tile embeddings from multiple PFMs into compact edge-oriented encoders. Instead of regressing individual teacher features, MuCoDi trains lightweight MobileOne and RepViT students with a contrastive distillation objective adapted from MoCo v3, where cached Virchow2, UNI2, and H-Optimus-1 embeddings replace momentum-encoder keys. We pretrain students on 14.3M TCGA tiles from only 11.8K WSIs and evaluate frozen encoders on 23 clinically curated downstream classification tasks. RepViT-based MuCoEdge students retain near-teacher performance while reducing model size by orders of magnitude: MuCoEdge-R2.3 and MuCoEdge-R1.5 reach 71.0% external AUROC, within 0.8 percentage points of the best teacher (Virchow2, 71.8%), while MuCoEdge-R2.3 obtains the best external F1 and the second-best AUPRC (51.8% and 53.3%). MuCoEdge-R1.0 reaches 70.9% AUROC with only 6.4M parameters and 1.12 GFLOPs. On a Raspberry Pi 5, sub-million-parameter MobileOne students achieve up to 605-fold single-tile speedup over Virchow2 while retaining 66.5% to 66.9% external AUROC, demonstrating that PFM-quality pathology representations can be moved toward practical edge deployment. Code is available at https://anonymous.4open.science/r/mucodi-6243.

Tim Lenz, Maurice Heide, Marco Gustav +2

EKFZ for Digital Health, TU Dresden, Dresden, Germany · Pathology, University of Augsburg, Augsburg, Germany · Bavarian Cancer Research Center (BZKF), Augsburg, Germany +3

Computational Pathology Pathology Foundation Models Histopathology Image Classification Edge ML Knowledge Distillation

Jul 5, 2026

The Good, the Bad, and the Brittle: Benchmarking Robustness and Generalisation of Histopathology Foundation Models

How robust and generalisable are pathology foundation models and have their scaling limites been reached? We benchmarked twelve pathology foundation models (PFMs) and ResNet baselines using our Robustness Evaluation and Enhancement Toolbox (REET) across eleven clinically realistic perturbations and a dissimilarity-driven Non-Redundant K-fold validation (NR-Kfold) protocol. We introduce a Perturbation Performance Index (PPI) to summarise accuracy trends under controlled perturbation sweeps and analyse robustness scaling with parameter count. We show that PFMs consistently outperform CNNs in both robustness and domain generalisation, yet model scaling shows diminishing returns: mid-sized models such (UNI2/Virchow-2 etc.) achieve comparable or greater resilience than larger systems. NR-Kfold analysis further reveals systematic accuracy loss and increased variability when training-test similarity is broken, underscoring the need for explicit distribution-shift evaluation. These findings suggest that the next generation of pathology foundation models must prioritise data quality, multimodality information and domain alignment over parameter count to achieve genuine clinical reliability.

Dhyey Yajnik, Amina Asif, Fayyaz Minhas

Predictive Systems in Biomedicine Lab, Tissue Image Analytics Centre, Department of Computer Science, University of Warwick, United Kingdom

Distribution Shift Robustness Neural Network Robustness Pathology Foundation Models Histopathology Image Classification Cross-Dataset Generalization

Jun 29, 2026

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

\mathtt{DICE}

, a plug-and-play framework that ensembles

K

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

\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,

\mathtt{DICE}

takes a crucial step toward translating PFMs into uncertainty-aware decision-support systems.

Gbègninougbo Aurel Davy Tchokponhoue, Sevda Öğüt, Ali Idri +2

EPFL, Lausanne, Switzerland · UM5, Rabat, Morocco

Pathology Foundation Models Deep Ensembles Uncertainty Calibration Whole-Slide Image Analysis

Jun 29, 2026

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.

Dominik Winter, Dominik Vonficht, Loïc Le Bescond +6

AstraZeneca Computational Pathology and Biomarkers, Munich, Germany · AstraZeneca, Early Oncology and Translation Medicine, Cambridge, UK

Computational Pathology Cross-Modal Alignment Pathology Foundation Models Oncology Multimodal Contrastive Learning Gene Expression Prediction from Histopathology Images+1

Jun 27, 2026

Mitigating Batch Effects in Histopathology via Language-Mediated Robust Embedding Generation

Pathology foundation models (PFMs) have demonstrated strong potential across clinical and scientific applications, yet their performance is often hindered by batch effects, which are non-biological variations across tissue source institutions (TSIs) that distort learned feature representations and impair generalization. Conventional mitigation strategies, such as stain normalization, offer limited success in addressing these high-dimensional, complex artifacts. We present GLMP (General-purpose LLM-Mediated Pathology model), a novel framework that generates robust numerical embeddings from histology image patches through an intermediate textual representation. By leveraging pretrained general-purpose multimodal large language models (MLLMs) and text encoders, GLMP effectively prioritizes biologically meaningful signals over TSI-specific artifacts, thereby improving cross-institutional generalization. To our knowledge, GLMP is the first pathology model to use text descriptions of histological features as an intermediate representation for generating numerical embeddings from histology images. Our results highlight the untapped potential of broad-domain, non-specialized MLLMs in computational pathology and introduce a new paradigm for building versatile, generalizable, and robust pathology models.

Yishu Zhang, Shushan Wu, Zhenzhong Zhang +8

University of North Carolina at Chapel Hill

Computational Pathology Pathology Foundation Models Medical Image Representation Learning

Jun 16, 2026

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.

Tianyu Liu, Ziqing Wang, Zhaokang Liang +12

Program of Computational Biology and Bioinforamtics, Yale University, USA · Broad Institute of MIT and Harvard, USA · These authors contributed equally to this work. +12

Pathology Foundation Models Clinical Prediction Oncology Multimodal Fusion Whole-Slide Image Analysis Microscopy Image Analysis

Jun 16, 2026

SegTME-UNI2: A Foundation Model-Based Framework for Generalisable Multiclass Cell Segmentation and LLM-Driven Tumour Microenvironment Characterisation in Histopathology

Characterising the TME from routine H&E-stained histology images requires simultaneous cell segmentation, biological feature extraction, and interpretable clinical reporting. We present SegTME-UNI2, a unified framework addressing all three requirements end-to-end: a segmentation backbone that converts raw H&E patches into per-nucleus class labels, a structured feature-extraction pipeline that turns those labels into quantitative TME descriptors, and a language-model narrative generator that turns those descriptors into clinician-readable text. At its core is UNI2-UperHoVer, a dual-head multiscale segmentation model that pairs UNI2 with two parallel UperNet decoders: one for six-class semantic segmentation and one for HV gradient regression enabling watershed-based nuclear instance separation. It is trained via a three-stage progressive pseudo-label curriculum, scaling from PanNuke (Stage 1, 0.25um/pixel) to TCGA-UT Scale-0 (Stage 2, 0.5um/pixel) and full 1.6M-patch, six-scale TCGA-UT (Stage 3, 0.5 to 1.0um/pixel). TCGA-UT's coarser, broader per-patch context than PanNuke's also permits a larger tile stride during whole-slide inference. This pipeline computes 22 per-patch compositional, morphological, spatial-entropy, and intercellular-distance metrics and translates them into six categorical phenotype labels and a standardised biological-token vocabulary, fine-tuned via NVIDIA BioNeMo that converts into clinically grounded narratives whose individual claims can be spot-checked directly against the underlying features. Qualitative validation on IGNITE NSCLC tiles shows the pipeline produces biologically coherent phenotype classifications and narratives despite inter-institutional stain variability and imperfect segmentation. The pseudo-labelled TCGA-UT dataset and UNI2-UperHoVer checkpoints are publicly released to support large-scale TME profiling and spatial biology research.

Wan Siti Halimatul Munirah Wan Ahmad, Faris Syahmi Samidi, Mohammad Badal Ahmmed +3

Department of Data Science and Artificial Intelligence, School of Computing and Artificial Intelligence, Faculty of Engineering and Technology, Sunway University, Bandar Sunway, Malaysia · Department of Electrical and Electronic Engineering, College of Engineering, Universiti Tenaga Nasional, Kajang, Malaysia · Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, Malaysia

Computational Pathology Medical Report Generation Histopathology Image Segmentation Instance Segmentation Pathology Foundation Models Oncology

Jun 15, 2026

Probing, Fusion, and Trustworthiness: A Systematic Evaluation of Foundation Model Representations for Multimodal Cancer Analysis

Foundation models (FMs) have emerged as powerful representation extractors for medical data, yet their generalizability to datasets under distribution shift remains underexplored. This work systematically evaluates FM-based representations on a suite of computational pathology tasks across two real-world commercial cohorts, IH-BC and IH-NSCLC, drawn from the licensed in-house (IH) oncology dataset. The analysis focuses on two modalities, whole-slide images and transcriptomic profiles, drawn from the IH multimodal data. We first benchmark unimodal probing performance across five FMs on eight downstream classification tasks, and find that image and omics representations carry complementary predictive signals. Then we investigate whether multimodal fusion can yield additional gains over unimodal baselines by comparing three image-omics fusion strategies built on paired representations. The trustworthiness of selected unimodal and multimodal pipelines is further assessed through conformal prediction. Our results show that FM representations achieve competitive performance on out-of-distribution data and that multimodal fusion helps mainly when no single modality dominates the signal. Conformal prediction reveals that in the majority of cases where a point prediction fails, the true diagnosis remains recoverable within the prediction set, reinforcing the value of uncertainty-aware inference for clinical support.

Jingyu Hu, Giuseppe Tripodi, Reed Naidoo +2

The Alan Turing Institute, London, United Kingdom · University of Manchester, Manchester, United Kingdom · The Institute of Cancer Research, London, United Kingdom +1

Computational Pathology Multimodal Robustness Pathology Foundation Models Multimodal Classification Oncology Multimodal Foundation Models+1

Jun 10, 2026

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.

Kai Standvoss, Miriam Hägele, Rosemarie Krupar +25

Aignostics, Germany · Institute of Pathology, Charité – Universitätsmedizin Berlin, Germany · Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Germany +9

Computational Pathology Pathology Foundation Models Oncology Histopathology Image Classification Medical Image Benchmarks Whole-Slide Image Analysis

Jun 9, 2026

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.

Sofiène Boutaj, Leo Fillioux, Maria Vakalopoulou +2

Université Paris-Saclay, CentraleSupélec, Gustave Roussy, INSERM, IHU PRISM, Cancer Data Science Unit, France · Université Paris-Saclay, CentraleSupélec, MICS Laboratory, France

Pathology Foundation Models Medical Image Benchmarks Whole-Slide Image Analysis

Jun 5, 2026

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/.

Bokai Zhao, Yiyang Zhang, Long Bai +3

DAMO Academy, Alibaba Group · Institute of Automation, Chinese Academy of Sciences · Hupan Lab

Pathology Foundation Models Medical Image Representation Learning Medical Image Benchmarks Whole-Slide Image Analysis Self-Supervised Visual Representation Learning

Jun 3, 2026

A Pathology Foundation Model for Gastric Cancer with Real-World Validation

Gastric cancer remains a major cause of cancer mortality, yet its histological and molecular heterogeneity complicates diagnosis and risk stratification. General-purpose pathology foundation models (PFMs) often plateau on fine-grained endpoints central to gastric cancer care, and few have undergone rigorous prospective validation or clinical reader studies. We present GRACE, a Gastric-specific foundation model for Real-world Assessment and Clinical dEcision support. GRACE was developed from multicenter gastric pathology datasets totaling 48,364 primarily HE-stained whole-slide images from 37,493 patients. When evaluated on 28 clinically relevant tasks, GRACE consistently outperformed representative pancancer PFMs, achieving a macro-AUC of 0.9188, with strong performance for precancerous lesion diagnosis (macro-AUC 0.9322), tumor histopathological assessment (macro-AUC 0.9119), molecular profiling (macro-AUC 0.8682), and prognostic prediction. Beyond benchmarking, GRACE's translational value was substantiated through a rigorous evidence chain. Under safety-gated criteria requiring 100% NPV for rule-out and 100% PPV for rule-in, GRACE streamlined review for up to 69.6% of malignancy-diagnosis cases and triaged 46.8% of MMR-IHC follow-up requests. This translational feasibility was further strengthened by a randomized crossover reader study of pathologist-AI collaboration. With GRACE assistance, diagnostic accuracy improved from 82.0% to 89.9%, yielding nearly twofold higher adjusted odds of a correct diagnosis (OR 1.987) alongside concurrent gains in sensitivity and specificity. AI assistance also reduced diagnostic time by 14.9%, elevated diagnostic confidence by 9.0%, and markedly improved inter-rater agreement. When calibrated to maintain non-inferior performance to senior pathologists, the AI-assisted workflow could triage 60.7% of atrophy and 82.7% of intestinal metaplasia cases.

Ling Liang, Jiabo Ma, Zhengyu Zhang +25

Department of Computer Science and Engineering, The Hong Kong University of Science and Technology, Hong Kong SAR, China · Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China · Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China +18

Computational Pathology Medical Diagnosis Clinical Decision Support Pathology Foundation Models Oncology Histopathology Image Classification

Jun 3, 2026

Do Foundation Models See Biology? Evaluating Attention Coherence with Spatial Transcriptomics in Glioblastoma

Whether attention maps from pathology foundation models capture genuine biology remains unknown, yet this question is critical for clinical trust and regulatory approval. We propose a spatial transcriptomics-based framework for orthogonal, hypothesis-free evaluation of attention and apply it to five pathology foundation models (CONCH v1.5, UNI v2, Virchow2, GigaPath, H-Optimus-1) and a ResNet50 baseline. Using attention-based multiple instance learning, we train single-task and multi-task models to predict five molecular alterations in glioblastoma on the CPTAC cohort, validate on an independent TCGA cohort, and evaluate biological coherence of attention maps against 87 transcriptional signatures using co-registered Visium spatial transcriptomics data from 18 samples. Internally, no single encoder dominates across all tasks, and external validation inverts internal performance rankings. Attention maps show a five-fold enrichment gradient from pathways (Cohen's d=0.329) to individual genes (d=0.055), indicating that attention captures emergent multi-gene transcriptional programs rather than individual molecular events. Spatially smooth attention maps do not imply biological coherence, and different encoders attend to distinct biological compartments. Our framework provides objective, quantitative assessment of what foundation models learn from histopathology, moving the field beyond qualitative saliency map review.

Dilakshan Srikanthan, Amoon Jamzad, Paul Wilson +5

Translational Medicine, School of Medicine, Queen’s University, Kingston, ON, Canada · School of Computing, Queen’s University, Kingston, ON, Canada · Department of Surgery, Queen’s University, Kingston, ON, Canada

Pathology Foundation Models Explainable Medical Image Analysis

May 29, 2026

Spatial Transcriptomics-Guided Alignment Enhances Molecular Profiling in Pathology Foundation Model

Comprehensive molecular profiling is essential for modern precision oncology but remains hindered by prohibitive costs, specimen exhaustion, and protracted turnaround times. While pathology foundation models (PFMs) have demonstrated potential for inferring molecular phenotypes from routine hematoxylin and eosin (H&E) whole-slide images (WSIs), current architectures primarily rely on vision-centric self-supervised learning or vision-language alignment, lacking the spatially resolved molecular supervision required to connect subtle morphological features with underlying genomic alterations. Spatial transcriptomics (ST) emerges as a transformative technology that enables transcriptomic quantification within intact tissue sections, thereby preserving the precise spatial link between histology and molecular profiles. In this study, we present a Spatial Transcriptomics-guided Alignment framework for Molecular Profiling (STAMP), which endows PFMs with intrinsic molecular awareness. To support this paradigm, we curated HumanST-1k, a human ST dataset spanning diverse anatomical organs and sequencing platforms. This atlas yields 1.8 million pairs of H&E patches and corresponding transcriptomic profiles, providing a corpus that links histological structures with their molecular states. To mitigate the technical noise inherent to raw transcriptomics, STAMP applies a pathway-informed alignment strategy that aggregates transcriptomic data into biologically functional pathways, which are subsequently integrated into PFMs via parameter-efficient fine-tuning. This alignment enriches the representation space of PFMs and unlocks their capacity to resolve sub-visual molecular signatures. The clinical utility of these augmented representations was validated through a multi-tier evaluation framework.

Fengtao Zhou, Yingxue Xu, Zhengyu Zhang +20

Department of Computer Science and Engineering, The Hong Kong University of Science and Technology, Hong Kong SAR, China · Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China · Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China +16

Spatial Transcriptomics Cross-Modal Alignment Pathology Foundation Models Molecular Representation Learning

May 29, 2026

When Are Multimodal Predictions Biologically Supported? A Diagnostic Evaluation Framework

Multimodal models in oncology can produce accurate predictions, but accurate prediction does not reveal whether the model has learned biology that is shared across modalities, biology confined to one modality, or spurious correlations that reflect confounders rather than genuine biology. We introduce DECAT, a model-agnostic post-hoc evaluation framework that classifies multimodal representations into four diagnostic scenarios for a given task and modality, using five null-referenced metrics and a rule-based decision procedure. The framework operates on learned representations, requires no knowledge of which specific confounder is present, and returns indeterminate when the evidence is insufficient. We validate DECAT on synthetic data across four multimodal model classes (over 2,500 trained representations) and on real data from 8,979 TCGA patients, evaluating both multimodal embeddings and five pretrained pathology foundation models. Entangled models (e.g., CLIP) achieve near-perfect shared biology detection but falsely claim shared biology in the majority of cases where it is absent on real foundation model embeddings. This false claim rate increases with confound strength so that larger cohorts and stronger representations produce more confident but still incorrect diagnoses. Applied to both multimodal TCGA embeddings and five pathology foundation models without paired RNA, DECAT detects confounding invisible to AUROC without requiring the confounder labels, as confirmed by post-hoc stratification.

Dylan Steiner, Gustavo Arango-Argoty, Gerald Sun +1

Oncology Data Science & AI, R&D, AstraZeneca, Boston, US

Pathology Foundation Models Multimodal Embedding Oncology Multimodal Model Evaluation Multimodal Understanding

May 28, 2026

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.

Mingyi He, Xinyi Guo, Xitong Ling +7

Beijing University of Chemical Technology · South China Normal University · Tsinghua University

Self-Supervised Pre-Training Pathology Foundation Models Whole-Slide Image Analysis

May 25, 2026

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.

Zhengrui Guo, Zhengyu Zhang, Jiabo Ma +23

Department of Computer Science and Engineering, Hong Kong University of Science and Technology, Hong Kong, China · Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China · Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China +15

Computational Pathology Clinical Decision Support Pathology Foundation Models Oncology Whole-Slide Image Analysis

May 25, 2026

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/.

Bokai Zhao, Yiyang Zhang, Yuanchi Zhu +6

School of Artificial Intelligence, University of Chinese Academy of Sciences. · Brainnetome Center, Institute of Automation, Chinese Academy of Sciences. · Beijing Key Laboratory of Brainnetome and Brain-Computer Interface, Institute of Automation, Chinese Academy of Sciences. +2

Pathology Foundation Models Medical Image Benchmarks Whole-Slide Image Analysis

May 24, 2026

Discrepancy Minimization Improves Cross-Hospital Robustness in Digital Pathology

Pathology foundation models (PFMs) have advanced rapidly in recent years and support training classifiers for a range of histopathology tasks. However, their robustness across hospitals remains limited: performance often degrades when training a classifier on data from one hospital and evaluating it on another target hospital. We address this challenge by fine-tuning PFMs with a local maximum mean discrepancy (LMMD) objective that applies to two settings: domain adaptation, where unlabeled target-hospital data is available, and domain generalization, where target-hospital data is unavailable at all. Experiments at both the patch- and slide-level show consistent improvements across multiple PFMs and tasks.

Ben Vardi, Dana Schonberger, Yuval Friedmann +4

Reichman University, Herzliya, Israel · Institute of Pathology, Sheba Medical Center, Ramat-Gan, Israel · Technion - Israel Institute of Technology, Haifa, Israel

Computational Pathology Unsupervised Domain Adaptation Healthcare Maximum Mean Discrepancy Domain Generalization Pathology Foundation Models+1

May 8, 2026

Beyond ViT Tokens: Masked-Diffusion Pretrained Convolutional Pathology Foundation Model for Cell-Level Dense Prediction

Cell-level dense prediction is central to computational pathology, but remains challenging due to fine-grained histological structures, strong domain shifts, and costly dense annotations. Existing ViT-based pathology foundation models rely on patch tokenization, which can disrupt spatial continuity and weaken local morphological details needed for cell-level prediction. To address this, we propose Masked-Diffusion Convolutional Foundation Models, termed ConvNeXt Masked-Diffusion (CMD), a self-supervised convolutional generative pretraining framework for dense pathology representation learning. CMD uses a fully convolutional ConvNeXt-UNet backbone, performs masked-diffusion pretraining in pixel space, and incorporates frozen pathology foundation model features through adaptive normalization. Experimental results demonstrate that CMD consistently outperforms existing ViT-based pathology foundation models and even surpasses state-of-the-art end-to-end segmentation methods while fine-tuning only a small number of task-specific parameters across multiple pathology dense prediction tasks. The advantage is particularly pronounced under limited annotation settings, where CMD exhibits stronger robustness and generalization ability. Our findings suggest that purely convolutional architectures can also serve as competitive pathology foundation models for cell-level dense prediction, achieving leading performance within the current ViT-dominated paradigm and providing a scalable, high-performance solution that better preserves histological structural priors for fine-grained pathology understanding.

Weiming Chen, Xitong Ling, Zhenyang Cai +5

1Tsinghua Shenzhen International Graduate School, Tsinghua University · 3Research Institute of Tsinghua, Pearl River Delta · 2The Chinese University of Hong Kong, ShenZhen

Computational Pathology Histopathology Image Segmentation Pathology Foundation Models Medical Image Segmentation Convolutional Neural Networks Medical Image Representation Learning+1

May 6, 2026

A Breast Vision Pathology Foundation Model for Real-world Clinical Utility

Pathology foundation models have shown strong retrospective performance, but whether such systems can support clinically relevant use remains unclear. This challenge is particularly important in breast cancer, where pathological assessment serves as the gold standard for diagnosis and guides treatment planning, surgical decision-making and risk stratification across pre-, intra- and post-operative stages. Here we present BRAVE, a breast-adaptive pathology foundation model developed and evaluated using a total resource of 101,638 breast whole-slide images from 32 sources across Asia, Europe and North America. We assessed BRAVE across 34 tasks in 82 cohorts spanning pre-operative biopsy, intra-operative frozen section and post-operative resection, using an evidence chain comprising retrospective benchmarking, clinically challenging scenarios, workflow-oriented clinical impact simulations, prospective observational validation with the thresholds locked in the retrospective cohorts and crossover pathologist-AI interaction studies. Across these settings, BRAVE supported practical roles in the clinical workflow, including safe exclusion of low-risk cases from routine review, AI-assisted second-review rescue of initially missed positives and prioritization of cases for further assessment. In prospective validation across three centres, BRAVE excluded 76.9% of negative biopsy cases (NPV 0.953) and 70.1% of negative frozen-section cases (NPV 0.973), and triaged 78.8% of post-operative subtyping cases as high-confidence clear-cut cases (NPV 1.000). In reader studies, AI assistance improved balanced accuracy from 88.5% to 95.1% (OR 3.14, P<0.001), with better efficiency, confidence and inter-rater agreement. BRAVE-derived scores also independently predicted disease-free survival (adjusted HR 4.79, P<0.001) and overall survival (adjusted HR 8.14, P<0.001).

Yingxue Xu, Zhengyu Zhang, Xiuming Zhang +32

Department of Computer Science and Engineering, The Hong Kong University of Science and Technology, Hong Kong SAR, China · Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China · Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China +18

Healthcare Clinical Decision Support Pathology Foundation Models Oncology Histopathology Image Classification Whole-Slide Image Analysis

May 5, 2026

DALPHIN: Benchmarking Digital Pathology AI Copilots Against Pathologists on an Open Multicentric Dataset

Foundation models with visual question answering capabilities for digital pathology are emerging. Such unprecedented technology requires independent benchmarking to assess its potential in assisting pathologists in routine diagnostics. We created DALPHIN, the first multicentric open benchmark for pathology AI copilots, comprising 1236 images from 300 cases, spanning 130 rare to common diagnoses, 6 countries, and 14 subspecialties. The DALPHIN design and dataset are introduced alongside a human performance benchmark of 31 pathologists from 10 countries with varying expertise. We report results for two general-purpose (GPT-5, Gemini 2.5 Pro) and one pathology-specific copilot (PathChat+) for sequential and independent answer generation. We observed no statistically significant difference from expert-level performance in four of six tasks for PathChat, 2/6 tasks for Gemini, and 1/6 tasks for GPT. DALPHIN is publicly released with sequestered, indirectly accessible ground truth to foster robust and enduring benchmarking. Data, methods, and the evaluation platform are accessible through dalphin.grand-challenge.org.

Carlijn Lems, Sander Moonemans, Natálie Klubíčková +53

Computational Pathology Healthcare Medical VQA Pathology Foundation Models Medical Image Benchmarks

May 4, 2026

Biological Spatial Priors Regularize Foundation Model Representations for Cross-Site MSI Generalization in Colorectal Cancer

Predicting microsatellite instability (MSI) status from routine hematoxylin and eosin (H&E) whole slide images (WSIs) offers a practical alternative to molecular testing, but models trained at one institution tend to generalize poorly to slides acquired at a different site. Foundation model representations, despite their generality, still encode site-specific texture alongside the conserved biological morphology underlying MSI. We investigate whether tile-level spatial priors derived from known MSI histology can guide these representations toward more site-invariant features. We introduce a biologically motivated spatial prior based on peripheral distance encoding, reflecting the Crohn's-like peripheral lymphocytic reaction at the tumor invasive margin, and evaluate a secondary local immune neighborhood encoding reflecting the lymphocyte-to-tumor ratio in each tile's immediate spatial neighborhood. Both priors are injected into a TransMIL aggregator before self-attention, allowing the transformer to integrate spatial biological context with UNI2-h or Virchow2 features across all attention layers. We evaluate six foundation model and MIL aggregator combinations as a reference, then assess the effect of each spatial prior. Training on TCGA-COAD (137 slides) and evaluating externally on TCGA-READ (50 slides) without retraining, peripheral distance encoding achieves MSI AUC 0.959 +/- 0.012 on COAD and MSS specificity 1.000 on READ, compared to 0.957 and 0.939 for the strongest reference configuration. Local immune neighborhood encoding achieves comparable internal AUC but lower cross-site specificity, suggesting margin proximity encodes a more site-invariant biological signal than local immune density. Results suggest biologically grounded spatial priors act as regularizers that reduce reliance on site-specific imaging patterns.

Dasari Naga Raju

Spatial Generalization Pathology Foundation Models Clinical Prediction Oncology Histopathology Image Classification

May 1, 2026

Semantic Context-aware mOdality fUsion Transformer (SCOUT): A Context-Aware Multimodal Transformer for Concept-Grounded Pathology Report Generation

Whole-slide images (WSIs) present a fundamental challenge for computational pathology due to their extreme resolution, multi-scale heterogeneity, and the requirement for clinically reliable interpretation. Although recent pathology foundation models have enabled fluent report generation, they often lack clinical grounding, failing to accurately represent key diagnostic concepts and relationships observed by pathologists. This limitation arises from the difficulty of integrating heterogeneous visual evidence spanning fine-grained cellular patterns, slide-level tissue architecture, and high-level diagnostic concepts, while maintaining interpretability and clinical coherence. Here we present SCOUT: Semantic Context-aware mOdality fUsion Transformer, a context-aware concept-grounded multimodal framework for pathology report generation that enables progressive conditioning of image representations by global slide information and explicit diagnostic concepts. The method integrates local histological patterns, whole-slide context, and expert-curated semantic descriptors within a unified learning paradigm, allowing visual features to be dynamically refined throughout the encoding process. By combining depth-aware contextual modulation with adaptive multimodal fusion during text generation, the framework produces clinically coherent reports while preserving complementarity across representational scales. Using CONCH1.5 features, we evaluate SCOUT against WSI-Caption, HistGen, and BiGen on TCGA-BRCA, MICCAI REG, and HistAI. SCOUT achieves the best BLEU-1 to BLEU-4 and METEOR scores on all datasets, plus the best ROUGE-L on TCGA-BRCA and MICCAI REG. On TCGA-BRCA, it reaches 0.436/0.303/0.202/0.156 BLEU-1/2/3/4 and 0.204 METEOR; on REG 2025, it achieves 0.865/0.834/0.805/0.780 and 0.568. These results support progressive contextual conditioning for grounded pathology report generation.

Suryakant Singh, Saarthak Kapse, Joel Saltz +1

Stony Brook University

Computational Pathology Medical Report Generation Pathology Foundation Models Multimodal Fusion Whole-Slide Image Analysis

Apr 28, 2026

Validation of Whole-Slide Foundation Models for Image Retrieval in TCGA Data

Foundation models are reshaping computational histopathology, yet their value for whole-slide image retrieval relative to strong patch-based and supervised aggregation baselines remains unclear. We benchmarked ten pipelines on 9,387 diagnostic slides spanning 17 organs and 60 diagnoses from The Cancer Genome Atlas (TCGA) using patient-level leave-one-patient-out evaluation. Methods included four pre-trained slide foundation models, a supervised attention-based multiple instance learning (ABMIL) aggregator on patch embeddings, and patch-level retrieval across five sampling densities. Performance varied more across organs and diagnoses than across architectures. Although the slide foundation model TITAN achieved the strongest overall results, its advantage was modest; ABMIL and patch-based methods reached comparable Top-1 and Top-3 accuracy, with no model consistently dominant. Morphologically distinctive entities approached ceiling performance, while rare, heterogeneous, and closely related subtypes remained challenging. Misclassifications aligned with organs exhibiting known inter-observer variability, suggesting an intrinsic ceiling for morphology-only retrieval. Performance was driven primarily by patch-level feature representations, with limited benefit from slide-level aggregation, indicating aggregation may be unnecessary in many settings. These findings argue against a universally optimal architecture and instead support organ-resolved benchmarking, diagnosis-aware or ensemble strategies, stronger feature representations, and multimodal retrieval frameworks. Notably, even the best model achieved only

\approx 68\% \pm 21\%

retrieval accuracy on TCGA, and some subtypes showed

0\%

accuracy across all methods, highlighting fundamental limitations of morphology-based representations and the need for substantial progress before reliable clinical deployment.

Tianhao Lei, Parsa Esmaeilkhani, Saghir Alfasly +5

KIMIA Lab, Artificial Intelligence and Informatics, Mayo Clinic, Rochester, MN, USA. · Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. · Department of Computer Science, Temple University, Philadelphia, PA, USA. +2

Pathology Foundation Models Oncology Medical Image Benchmarks Multiple Instance Learning Whole-Slide Image Analysis

Apr 27, 2026

Benchmarking Pathology Foundation Models for Breast Cancer Survival Prediction

Pathology foundation models (PFMs) have recently emerged as powerful pretrained encoders for computational pathology, enabling transfer learning across a wide range of downstream tasks. However, systematic comparisons of these models for clinically meaningful prediction problems remain limited, especially in the context of survival prediction under external validation. In this study, we benchmark widely used and recently proposed PFMs for breast cancer survival prediction from whole-slide histopathology images. Using a standardized pipeline based on patch-level feature extraction and a unified survival modeling framework, we evaluate model representations across three independent clinical cohorts comprising more than 5,400 patients with long-term follow-up. Models are trained on one cohort and evaluated on two independent external cohorts, enabling a rigorous assessment of cross-dataset generalization. Overall, H-optimus-1 achieves the strongest survival prediction performance. More broadly, we observe consistent generational improvements across model families, with second-generation PFMs outperforming their first-generation counterparts. However, absolute performance differences between many recent PFMs remain modest, suggesting diminishing returns from further scaling of pretraining data or model size alone. Notably, the compact distilled model H0-mini slightly outperforms its larger teacher model H-optimus-0, despite using fewer than 8% of the parameters and enabling significantly faster feature extraction. Together, these results provide the first large-scale, externally validated benchmark of PFMs for breast cancer survival prediction, and offer practical guidance for efficient deployment of PFMs in clinical workflows.

Fredrik K. Gustafsson, Constance Boissin, Johan Vallon-Christersson +2

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden · Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden · Department of Engineering Science, University of Oxford, Oxford, UK +1

Cancer Survival Prediction Survival Analysis Pathology Foundation Models Oncology Medical Image Benchmarks Whole-Slide Image Analysis

Apr 26, 2026

Weakly Supervised Multicenter Nancy Index Scoring in Ulcerative Colitis Using Foundation Models

Histologic assessment of ulcerative colitis (UC) activity is an important endpoint in clinical trials and routine care, but manual grading with indices such as the Nancy histological index (NHI) is time-consuming and prone to observer variability. While computational pathology methods can automate scoring, many approaches depend on dense region-level annotations, which are costly to obtain, particularly in heterogeneous, multicenter cohorts. We propose a weakly supervised multiple instance learning (MIL) approach for whole-slide images that learns from case- and slide-level NHI labels, leveraging foundation models. Our method targets clinically relevant endpoints, including neutrophilic activity and derived Nancy-low/high groupings, enabling full five-grade NHI prediction. On a multicenter dataset of H&E-stained colon biopsies from three hospitals (2019-2025), we evaluate multiple foundation model encoders and aggregation strategies. We find that foundation model choice and resolution substantially affect performance, with Virchow2 providing the most consistent gains, and that a simple ensembling rule improves five-grade NHI prediction compared to a hierarchical gating baseline. Overall, our results demonstrate that weakly supervised MIL with modern foundation-model representations can provide robust, interpretable UC histology activity assessment in realistic multicenter settings.

Adam Kukučka, Ondřej Fabián, Vít Musil +1

Masaryk University, Faculty of Informatics, Brno, Czech Republic · Institute of Clinical and Experimental Medicine, Prague, Czech Republic

Computational Pathology Pathology Foundation Models Weakly Supervised Learning Histopathology Image Classification Multiple Instance Learning Whole-Slide Image Analysis

Apr 23, 2026

Attention-based multiple instance learning for predominant growth pattern prediction in lung adenocarcinoma wsi using foundation models

Lung adenocarcinoma (LUAD) grading depends on accurately identifying growth patterns, which are indicators of prognosis and can influence treatment decisions. Common deep learning approaches to determine the predominant pattern rely on patch-level classification or segmentation, requiring extensive annotations. This study proposes an attention-based multiple instance learning (ABMIL) framework to predict the predominant LUAD growth pattern at the whole slide level to reduce annotation burden. Our approach integrates pretrained pathology foundation models as patch encoders, used either frozen or fine-tuned on annotated patches, to extract discriminative features that are aggregated through attention mechanisms. Experiments show that fine-tuned encoders improve performance, with Prov-GigaPath achieving the highest agreement (\k{appa} = 0.699) under ABMIL. Compared to simple patch-aggregation baselines, ABMIL yields more robust predictions by leveraging slide-level supervision and spatial attention. Future work will extend this framework to estimate the full distribution of growth patterns and validate performance on external cohorts.

Laura Valeria Perez-Herrera, M. J. Garcia-Gonzalez, Karen Lopez-Linares

* Vicomtech Foundation, Basque Research and Technology Alliance (BRTA) · ± eHealth Group, Bioengineering Area, Biogipuzkoa Health Research Institute

Computational Pathology Pathology Foundation Models Oncology Multiple Instance Learning Whole-Slide Image Analysis