Histopathology Image Classification

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9 papers in the last four weeks, up 29% on the four weeks before. 0.1% of all new papers.

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Latest papers 76

Jul 5, 2026cs.CV

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

Jul 3, 2026cs.CV

Semantic Segmentation-Driven Image-Level Diagnosis of Liver Cancers in Hematoxylin and Eosin Histopathology Images

As hematoxylin & eosin (H&E) staining constitutes the primary entry point in routine diagnostic workflows, computer-aided diagnosis from whole-slide H&E images is of particular clinical relevance. However, substantial variability in specimen preparation, staining protocols, and scanning conditions, together with inherent uncertainty in expert pixel-level annotations, makes automated analysis of H&E-stained images challenging. In this study, we propose a semantic segmentation-based framework for image-level diagnosis, grounded in the clinically motivated assumption that each histopathological image corresponds to a single cancer type. Image-level predictions are obtained by assigning the class of the dominant pixel-level label in the segmentation output. To ensure clinical relevance, we adopt the nnU-Net architecture and train it on a publicly available dataset collected in our study with pixel-level annotations for three liver cancer types: hepatocellular cacrcinoma (HCC; 55 images from 30 patients), cholangiocellular carcinoma (CCA; 55 images from 29 patients), and colorectal metastatic adenocarcinoma (CMA; 60 images from 30 patients). Annotations were independently provided by four pathologist. We hypothesize that the combination of stain normalization and semantic segmentation mitigates domain shift and reduces sensitivity to annotation noise. Five-fold cross-validation yielded balanced accuracy of 0.975 (HCC), 0.950 (CCA), and 1.000 (CMA), comparable to results obtained with immunohosthochemical staining and superior to several deep learning models trained on patch-level annotations. The proposed framework has the potential to support pathologists in prioritizing immunohistochemical marker selection, thereby reducing diagnostic costs and turnaround time. Integration with immunohistochemical findings improve overall diagnostic reliability.

Ivica Kopriva, Dario Sitnik, Arijana Pacic +3

Division of Computing and Data Science, Ruđer Bošković Institute, Bijenička cesta 54, Zagreb Croatia · Sitnik Ventures UG, Lautensackstr. 25, 80687 Munich, Germany · Department of Pathology and Cytology, Dubrava University Hospital, Avenija Gojka Šuška 6, 10000 Zagreb, Croatia +2

Computational Pathology Histopathology Image Segmentation Medical Image Segmentation Oncology Histopathology Image Classification

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

Chaeyeon Lee, Khang Nguyen Quoc, Jinsol Song +3

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

Computational Pathology Hierarchical Classification Histopathology Image Classification Multiple Instance Learning Whole-Slide Image Analysis

Jun 28, 2026cs.CV

CellDETR: A Detection-Guided Framework for Scalable Cell Representation Learning from Histopathology Images

Recent advances in pathology foundation models have substantially improved patch and slide level representation learning from whole-slide images (WSIs).However, cell-level representations learning remain underexplored, limiting cell resolved interpretability, biological discovery, and clinical translation. We propose CellDETR, a detection-guided framework built on Deformable DETR for scalable cell representation learning from WSIs. By introducing location feature decoupling and box-constrained attention mechanism, CellDETR enables automated extraction of cell-level embeddings, and outperform existing state-of-the-art methods in supervised cell classification on PanNuke data. In addition, by incorporating contrastive learning design, we build a CellDETR-based pretraining model for scalable cell representation learning from unlabeled WSIs, which improves downstream cell classification performance. Furthermore, we show that after pretraining with Xenium spatial transcriptomics-derived cell annotations, CellDETR achieves accurate cross-dataset cell classification, demonstrating the transferability and biological relevance of the learned cell embeddings. Together, CellDETR provides a scalable route toward general cell-level representation learning framework for interpretable computational patholog

Shikang Zhang, Guojun Li, Yicong Mao +1

Zhejiang University of Technology · Tianjin University · Hangzhou Institute of Medicine, Chinese Academy of Sciences

Representation Learning Detection Transformer Histopathology Image Classification

Jun 27, 2026cs.CV

Predicting Metastatic Risk from Primary Cancer Tissue Architecture via Distance-Aware Spatial Modeling

Predicting distant metastasis from the digital H & E slides of the primary tumor is a critical yet challenging task in computational pathology. Multiple Instance Learning (MIL) approaches can attend to subdomains in whole slide images (WSIs) that harbor features of pre-metastatic cancer regions. However, conventional MIL models largely treat tissue patches as unordered bags, discarding the spatial layout that defines how these regions are arranged and interact across the tissue. We propose that metastatic risk is shaped not only by local patch appearance, but also by the geometric organization of patches in the WSI and the interaction between the tissue compartments. To this end, we introduce Distance-aware Tissue Modeling for Multiple Instance Learning (DTMF-MIL), a spatial MIL framework that reinforces feature embeddings with explicit distance priors. By computing signed distance functions (SDFs) to capture regions with similar features, and representing each patch with radial-basis distance responses and local SDF statistics, DTMF-MIL learns positions of patches with respect to regional interiors and boundaries. The interactions between similar patches are contextualized across local tissue neighborhoods and used to guide slide-level attention while pooling patch feature evidence for metastasis prediction. We evaluate DTMF-MIL for prediction of distant prostate cancer metastasis in an internal prostate needle-biopsy cohort (IPC) from a large hospital system and on public TCGA-COAD and TCGA-KIRC datasets across multiple pathology foundation-model backbones. Across most dataset, backbone, and metric combinations, DTMF-MIL achieves the strongest results consistently.

Sandesh Pokhrel, Hamid Manoochehri, Beatrice S Knudsen +1

Department of Electrical and Computer Engineering, University of Utah · Scientific Computing and Imaging Institute, University of Utah · Department of Pathology, University of Utah

Computational Pathology Clinical Outcome Prediction Oncology Histopathology Image Classification Multiple Instance Learning

Jun 23, 2026cs.CV

Transformation Behavior of Images in Latent Space

Training of neural networks for histopathology classification tasks typically relies on data encoding into latent space, which reduces complexity and improves performance. There are several encoder networks available, either pretrained on general image datasets such as ImageNET, or specifically on histopathological images. Training of encoder networks should be adapted to downstream tasks, allowing encoding of biologic/diagnostic content while rendering networks invariant to label-irrelevant transformations. This paper investigates the effect of classical image transformation on the latent space, using networks provided by Lunit Inc. and Bioptimus, both focusing on pathological images, and by Meta Research Team. We assess variance of embeddings resulting from standard data transformations by comparing original and transformed image embeddings and by contrasting them with random, unrelated embeddings, using image tiles from hematoxylin/eosin-stained sections available in a colorectal tissue dataset and the publicly accessible TCGA dataset. Our findings show that embeddings of original and transformed images are closer to each other than to random embeddings, indicating robustness to transformations. However, they are not fully invariant, revealing that the encoder networks do not completely neutralize transformation effects in latent space, explaining why transformation-mediated augmentation of datasets can improve performance. Significant differences were observed between general and histopathology-specific encoder networks.

Christian Zöllner, Mozzam Motiwala, Aysel Ahadova +4

Department of Applied Tumor Biology Institute of Pathology Heidelberg University Hospital · Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany · National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany +5

Histopathology Image Classification Invariant Representation Learning Medical Image Representation Learning

Jun 21, 2026q-bio.QM

Performance and Interpretability of Convolutional, Transformer, and Hybrid Deep Learning Models in Colorectal Histology Classification

Deep learning has become an important tool in computational pathology, enabling automated analysis of histopathological images. While convolutional neural networks (CNNs) have traditionally dominated this field, transformer-based and hybrid architectures have recently demonstrated promising performance. However, comprehensive comparisons of these approaches for colorectal histopathology remain limited. This study evaluated twelve ImageNet-pretrained CNN, transformer, and hybrid architectures using the Kather colorectal histopathology dataset containing 5,000 image tiles from eight tissue classes. All models were trained using a standardized transfer-learning and fine-tuning protocol and assessed using multiple performance metrics, including accuracy, precision, sensitivity, specificity, F1-score, ROC-AUC, Cohen's kappa, and Matthews correlation coefficient. All evaluated models achieved high classification performance, with accuracies ranging from 93.2% to 97.1%. EVA-02 achieved the highest overall performance (97.1% accuracy, 97.0% F1-score), closely followed by ViT-B/16. Among CNNs, ResNet34 and ConvNeXt-Tiny demonstrated highly competitive performance, achieving accuracies of 96.4% and 96.3%, respectively. Transformer architectures generally produced the strongest results across evaluation metrics, although the performance gap between the best transformer and CNN models was relatively small. Per-class analysis showed consistently strong classification performance across all tissue categories, with Complex Stroma representing the most challenging class. Overall, transformer-based architectures achieved the highest predictive performance, whereas modern CNNs provided a favorable balance between accuracy and model complexity. These findings provide a comprehensive benchmark of major deep learning paradigms for colorectal histopathology classification.

Reza Bozorgpour

College of Engineering & Applied Science, Department of Biomedical Engineering, University of Wisconsin-Milwaukee, Milwaukee, WI, USA

Hybrid CNN-Transformer Architectures Vision Transformer Convolutional Neural Networks Histopathology Image Classification Medical Image Benchmarks

Jun 19, 2026eess.IV

Configurable Algorithms for Histopathologic Cancer Detection on Quantum Hardware

Histopathologic cancer detection is challenging due to tissue variability, staining differences, and subtle visual distinctions between disease classes. We propose two quantum algorithms for this task: a configurable dual-gradient CSWAP circuit (DG-CSWAP) that computes multi-directional edge responses in a single execution via per-pixel local Ry encoding, and a hardware-efficient destructive swap circuit (DG-DST) natively matched to quantum processing unit (QPU) gate sets at substantially lower circuit complexity. We prove algebraic equivalence between DG-CSWAP and DG-DST, enabling a two-circuit QPU validation strategy. A three-stage NISQ mitigation pipeline, including readout error correction, bias subtraction, and slope regression, reduces single-pixel hardware MSE by ~8x. Validated on five quantum processors via Amazon Braket, the method achieves inter-platform Pearson r ~ 0.93-0.94 across all local-simulator pairs. Compared to a prior Quantum Fourier Transform (QFT) based amplitude-encoding baseline requiring 12-qubit global state preparation and a three-model ensemble (85.55% on PatchCamelyon), the proposed method uses shot-based measurements, executes on real quantum hardware, and achieves 79.80% accuracy with a single ResNet-50. A Lite configuration delivers a 17x preprocessing speedup at a 2.59% accuracy cost. To the best of our knowledge, this is the first quantum hardware implementation study with noise mitigation for histopathologic image classification.

Nandika Goyal, Glen Uehara, Andreas Spanias

SenSIP Center, School of ECEE · Arizona State University

Edge Inference Hybrid Quantum-Classical ML Histopathology Image Classification Quantum Error Mitigation

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.

Sungrae Hong, Jiwon Jeong, Soeun Cheon +5

Korea Advanced Institute of Science and Technology, Daejeon, South Korea · Seegene Medical Foundation, Seoul, South Korea

Computational Pathology Histopathology Image Classification Multiple Instance Learning Whole-Slide Image Analysis

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.

Kian R. Weihrauch, Thomas A. Buckley, William Lotter +1

Massachusetts Institute of Technology, Cambridge, MA · Harvard Medical School, Boston, MA · Dana-Farber Cancer Institute, Boston, MA

Multimodal Large Language Models Histopathology Image Classification Medical Image Benchmarks Whole-Slide Image Analysis

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.

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 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.

Yonghan Shin, Won-Ki Jeong

Department of Computer Science and Engineering, Korea University, Seoul, Korea

Histopathology Image Classification Knowledge Distillation Multiple Instance Learning Whole-Slide Image Analysis

Jun 4, 2026cs.CV

Symb-xMIL: Symbolic Explanations for Multiple Instance Learning in Digital Pathology

Explanations of multiple instance learning (MIL) models are widely used for validation and discovery in digital histopathology. Existing methods primarily rely on heatmaps that highlight influential regions but do not explain how evidence from different tissue regions is combined to produce a prediction. This limits interpretability, especially when decisions depend on interactions between tissue features. We introduce Symbolic explainable MIL (Symb-xMIL), a post-hoc explanation framework that quantifies how a MIL model's behavior aligns with human-readable decision rules, expressed as logical relationships (e.g., AND, OR, NOT) between input features. These alignment scores reveal semantic patterns underlying the model's predictions. We evaluate Symb-xMIL on synthetic and real-world histopathology datasets. On synthetic MIL data, Symb-xMIL reliably recovers ground-truth logical rules. In a clinical tumor detection task, the best-aligned rules uncover heterogeneous decision patterns and expose hidden model errors. On an HPV-prediction task on TCGA-HNSCC, a cohort of head and neck cancer, our framework refines patient survival stratification beyond HPV status with potential clinical relevance. Overall, Symb-xMIL extends MIL explainability beyond visual attribution toward structured, rule-based reasoning, enabling more transparent and semantically grounded interpretation of model predictions.

Yanqing Luo, Julius Hense, Niklas Prenißl +4

Berlin Institute for the Foundations of Learning and Data, Berlin, Germany · Machine Learning Group, Technische Universität Berlin, Berlin, Germany · Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany +10

Computational Pathology Explainable Medical Image Analysis Histopathology Image Classification Multiple Instance Learning

Jun 3, 2026cs.CV

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

May 28, 2026cs.CV

Parameter-Efficient Subspace Decoupling ViT for Mitigating Multi-Task Negative Transfer in Histological Scoring

Histological scoring is essential for diagnosing Non-Alcoholic Fatty Liver Disease (NAFLD), yet its automation remains challenging due to the high annotation cost and negative transfer among the strongly correlated NAFLD Activity Score (NAS) indicators in multi-task learning. To address this issue, we propose a subspace-decoupled multi-task Vision Transformer (ViT) that integrates lightweight task-specific Adapters with orthogonality-based constraints. This design constructs independent feature subspaces for steatosis, ballooning, and inflammation, effectively reducing task interference while retaining shared representations. We further construct a curated multi-task mouse NAFLD histology dataset with expert annotations for all NAS components. Experimental results demonstrate that the proposed method improves multi-task stability and generalization with substantially reduced computational cost compared to training separate single-task models. The code and the curated dataset have been prepared and will be made publicly available upon acceptance to support reproducibility.

Youhan Huang, Jiajun Li, Yilin Fang +2

1Beijing University of Posts and Telecommunications, Beijing, China · 2Beijing University of Chemical Technology, Beijing, China · 3Capital Medical University, Beijing, China

Vision Transformer Multi-Task Learning Histopathology Image Classification Negative Transfer

May 23, 2026cs.AI

ConceptM $^3$ oE: Concept-Guided Multimodal Mixture of Experts for Interpretable Computational Pathology

Healthcare models are transitioning from unimodal prediction toward multimodal reasoning over heterogeneous diagnostic inputs. In computational pathology, for complex tumor subtypes where morphology alone can be challenging to distinguish, pathology reports and molecular measurements may provide additional diagnostic evidence alongside whole-slide images, yet existing models often fail to clarify how diverse signals assemble into recognizable diagnostic concepts. We propose ConceptM

^3

oE (Concept Multimodal MoE), which embeds concept formation directly within interaction-aware mixture-of-experts (MoE) pathways. The architecture decomposes evidence into modality-specific, redundant, and synergistic experts, which are then projected into structured concept bottlenecks mapping latent features to a hierarchy of morphology and biomarker concepts. To prevent the information loss typical of interpretable bottlenecks, we utilize residual pathways within each expert to allow task-relevant signals to flow both through the concepts and directly to the final task prediction, so that high performance is maintained alongside interpretability. Across an institutional pediatric brain tumor cohort and a public glioma cohort, the framework delivers competitive performance to unconstrained models while producing reasoning traces validated by an independent neuropathologist. In data-limited regimes, ConceptM

^3

oE improves limited-data performance, increasing macro-F1 from 56.41% to 66.70% at small training sizes compared to non-concept-informed baselines, while also showing faster training convergence consistent with the regularizing effect of concept learning. This work offers a scalable path toward high-performance medical AI that is inherently verifiable and better aligned with the complex decision-making of clinical practice.

Xuan Wang, Zhongling Xu, Gopi Kannedhara +13

University of Texas at Austin, Austin, TX, USA · University of North Carolina at Chapel Hill, NC, USA · Dell Children’s Medical Center, Austin, TX, USA +2

Computational Pathology Concept Bottleneck Models Healthcare Interpretable ML Multimodal Classification Oncology+4

May 19, 2026cs.CV

Thinking in Scales: Accelerating Gigapixel Pathology Image Analysis via Adaptive Continuous Reasoning

Traditional whole slide image (WSI) analysis methods typically rely on the multiple instance learning (MIL) paradigm, which extracts patch-level features at high magnification and aggregates them for slide-level prediction. However, such exhaustive patch-level processing is computationally expensive, severely limiting the efficiency and scalability of WSI analysis. To address this challenge, we propose PathCTM (a Pathology-oriented Continuous Thought Model) that enables token-efficient scale-space continuous reasoning for gigapixel WSIs. PathCTM formulates diagnostic inference as a dynamic sequential information pursuit. It progressively transitions from low-magnification global to high-magnification local inspection, and adaptively terminates inference when sufficient evidence is gathered to effectively bound decision uncertainty. Specifically, it uses conditional computation for dynamic scale switching with attention-guided region pruning, coupled with confidence-aware early stopping. Extensive experiments demonstrate that, compared with standard MIL-based methods, PathCTM reduces the number of required image patches by 95.95% and shortens inference time by approximately 95.62%, while maintaining AUC without degradation. Code is available at https://github.com/JSGe-AI/PathCTM.

Jiusong Ge, Yingkang Zhan, Wenjie Zhao +13

School of Computer Science and Technology, Xi’an Jiao-tong University, Xi’an, China · Department of Transmedia Art, Xi’an Academy of Fine Arts, Xi’an, China · Language Technology Lab, University of Cambridge, Cambridge, U.K. +3

Computational Pathology Adaptive Inference Histopathology Image Classification Whole-Slide Image Analysis

May 18, 2026cs.CV

Beyond Morphology: Quantifying the Diagnostic Power of Color Features in Cancer Classification

In histopathology, human experts primarily rely on color as a means of enhancing contrast to interpret tissue morphology, whereas machine vision models process color as raw statistical information. This distinction raises a fundamental question: to what extent can pixel intensity alone, independent of structural and morphological cues, support cancer classification? To address this question, we systematically evaluated the standalone discriminative power of global color features while deliberately excluding all morphological information. Specifically, we extracted statistical color moments and discretized RGB and HSV color histograms, and assessed their performance across ten diverse experimental settings using classical machine learning classifiers. Our results demonstrate that color features alone can achieve strong performance in binary diagnostic tasks (e.g., benign versus malignant), with classification accuracies reaching up to 89%. This performance is likely attributable to global chromatic shifts associated with malignancy. Importantly, these simple color-based representations consistently outperformed random baselines by a substantial margin, indicating that raw color distributions encode a non-random and diagnostically relevant signal for cancer detection. Consequently, this study suggests that simple, computationally efficient color features can serve as an effective pre-screening tool. By identifying samples with strong chromatic indicators of malignancy, these lightweight models could function as a first-pass triage system, reducing the computational burden on complex deep learning architectures.

Farnaz Kheiri, Shahryar Rahnamayan, Masoud Makrehchi

Dept. of Electrical, Computer and Software Engineering Ontario Tech University Oshawa, Ontario, Canada · Dept. of Engineering Brock University St. Catharines, Ontario, Canada

Computational Pathology Oncology Histopathology Image Classification

May 18, 2026cs.CV

Geometry-Aware Uncertainty Coresets for Robust Visual In-Context Learning in Histopathology

Vision-language models (VLMs) can couple visual perception with open-ended clinical reasoning, making them attractive for computational histopathology. However, fine-tuning billions of parameters on scarce, expert-annotated pathology data is prohibitive, while in-context learning (ICL), which conditions the VLM on demonstrative image-text pairs without parameter updates, suffers from high sensitivity to which examples are selected and how the query is phrased, producing unreliable diagnostics. Existing selection strategies rely on query-dependent nearest-neighbour retrieval that ignores global data structure, require costly parameter updates, or disregard the joint vision-text embedding geometry of VLMs. We propose GAUC, a training-free coreset selection method operating directly in the pre-trained multimodal embedding space. GAUC jointly optimises three objectives: (1) a Maximum Mean Discrepancy term enforcing distributional fidelity between coreset and full dataset, (2) an Effective Mutual Information Difference regulariser bounding performance degradation under prompt paraphrases by exploiting the VLM's joint vision-text alignment, and (3) a predictive-uncertainty (entropy) penalty suppressing ambivalent, hallucination-prone outputs. On CRC-100K and MHIST across multiple open-source VLM architectures, GAUC \emph{matches} the accuracy of the strongest ICL selection and dataset-distillation baselines while substantially improving calibration, prompt robustness, and hallucination rates, all without a single gradient update.

Franciskus Xaverius Erick, Johanna Paula Müller, Bernhard Kainz

FAU Erlangen-Nürnberg, Erlangen, DE · Department of Computing, Imperial College London, London, UK

VLM Robustness In-Context Learning Medical VLMs Coreset Selection Histopathology Image Classification

May 17, 2026cs.CV

GCE-MIL: Faithful and Recoverable Evidence for Multiple Instance Learning in Whole-Slide Imaging

Multiple instance learning (MIL) is the standard approach for whole-slide image (WSI) classification and survival prediction, where attention-based models ag gregate patch features into slide-level predictions. These models treat attention weights as evidence for their predictions, but attention is optimized for classi fication, not for identifying which patches actually support the diagnosis. This conflation leads to three failures: selected patches are insufficient (keeping them alone drops Macro-F1 by 0.078), unnecessary (removing them barely changes the prediction), and unrecoverable (continuous attention scores disagree with discrete patch subsets used at inference). The central premise is that evidence quality should be optimized directly through explicit criteria- Sufficiency, Necessity, and Recov erability (S/N/R)- rather than inherited as a byproduct of classification. GCE-MIL is a backbone-agnostic wrapper implemented through three injection modes and three evidence components: a grounding mechanism that aligns selection with domain-specific concepts, noisy-OR coverage that acts as a differentiable proxy for interventional evidence search, and threshold-plus-repair recovery that converts continuous selectors into discrete subsets through marginal-guided repair. Across 9 backbones and 9 datasets (81 configurations), GCE-MIL improves average Macro-F1 by 0.024 and C-index by 0.014, reduces the continuous-discrete gap by 4-7, and increases complement degradation by 2-4. With optional tile prefiltering after discrete recovery, inference runs up to 5 faster while retaining 0.989 full-bag utility.

Xiangyu Li, Ran Su

College of Intelligence and Computing Tianjin University

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

May 17, 2026cs.CV

Spatial Blindness in Whole-Slide Multiple Instance Learning

Whole-slide MIL models are often called context-aware once graphs, Transform ers, or state-space modules are placed above patch embeddings. We show that this label can be deceptive. On pathology tasks where tissue architecture is part of the diagnostic signal, several strong MIL baselines retain nearly unchanged slide level AUC after patch coordinates are permuted. Their predictions are accurate, but largely compositional. We refer to this failure mode as spatial blindness. Our explanation is optimization-based: dense appearance statistics are learned early under slide-level supervision, leaving weak gradients for sparse spatial relations. ResTopoMIL addresses the issue by first fitting a permutation-invariant prototype histogram and then freezing it while a lightweight graph branch learns the residual under a coordinate-shuffling constraint. The architecture is simple by design; the intervention is in how the spatial branch is trained. Across 9 public WSI bench marks, ResTopoMIL improves classification and survival prediction with 1.15M parameters, restores sensitivity to coordinate perturbation, and gives stronger lo calization evidence on CAMELYON-16.

Xiangyu Li, Ran Su

College of Intelligence and Computing Tianjin University Tianjin, China

Histopathology Image Classification Multiple Instance Learning Whole-Slide Image Analysis

May 15, 2026cs.CV

Diffusion Attention Expert Model for Predicting and Semi-automatic Localizing STAS in Lung Cancer Histopathological Images

Accurate intraoperative and postoperative diagnosis of spread through air spaces (STAS) is essential for guiding surgical decisions and postoperative management in lung cancer. However, histopathological assessment is labor-intensive and is prone to missed or incorrect diagnoses. We propose a Diffusion Attention Expert Model (DAEM) to detect STAS in frozen sections (FSs) and paraffin sections (PSs). Its diffusion attention expert module leverages full attention aggregation to learn multi-scale features from histopathological images, while a dual-branch architecture strengthens multi-scale feature representation. On an internal dataset, DAEM achieves AUCs of 0.8946 for FSs and 0.9112 for PSs. Validation on external multi-center datasets from eight institutions demonstrates strong generalizability and interpretability. Using tumor microenvironment (TME) features in PSs, we further enable semi-automatic measurement of STAS location and its distance from the primary tumor. Several quantitative TME metrics are identified as potential biomarkers for STAS, including micropapillary-type STAS. Overall, DAEM offers a clinically actionable framework for STAS assessment by enabling accurate and interpretable detection on FSs and PSs, supporting postoperative risk stratification through quantitative TME-based analysis.

Liangrui Pan, Jiadi Luo, Yuxuan Xiao +13

College of Computer Science and Electronic Engineering, Hunan University, Changsha, 410082, China · Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China · Hunan Clinical Medical Research Center for Cancer Pathogenic Genes Testing and Diagnosis, Changsha, Hunan, 410011, China +8

Computational Pathology Oncology Explainable Medical Image Analysis Histopathology Image Classification Medical Image Localization

May 12, 2026eess.IV

Are Compact Rationales Free? Measuring Tile Selection Headroom in Frozen WSI-MIL

Whole-slide image (WSI) multiple instance learning (MIL) classifiers can achieve strong slide-level AUC while leaving the full-bag prediction opaque. Attention scores are widely reused as post-hoc explanations, but high attention can reflect aggregation preference rather than a compact, model-sufficient rationale. We study post-hoc rationale highlighting for frozen WSI-MIL: given a trained classifier, can its slide-level prediction be recovered from a compact, output-consistent tile subset without retraining the backbone? We instantiate this with Finding Optimal Contextual Instances (FOCI), a lightweight rationale-readout layer over a frozen MIL backbone. FOCI is trained with model-output sufficiency and exclusion objectives over keep/drop tile subsets, evaluated with an insertion-style Sequential Reveal Protocol (SRP) adapted to WSI-MIL, and summarized by the Selection Headroom Index (SHI). Across three WSI benchmarks and seven MIL backbones, FOCI reveals that compact rationales are selection-headroom dependent: transformer and multi-branch attention aggregators can admit compact rationales, near-minimal attention-pooling baselines enter a selection-saturation regime, and hard-selection backbones can conflict with an external readout. For TransMIL, relative to its documented CLS-proxy ranking, FOCI reduces the Minimum Sufficient K (MSK) tile count by 32-56% across benchmarks, while ACMIL+FOCI attains the highest mean SHI (+0.465). Deletion-based perturbation and selected-only downstream evaluation provide complementary checks. These results position FOCI as a model-level interpretability and audit layer: selected tiles are not claims of clinical or pathologist-level diagnostic sufficiency, but candidate rationales that offer a compact, reviewable view of when a frozen MIL prediction can be localized to a small output-consistent subset.

Hyun Do Jung, Jungwon Choi, Soojung Choi +2

Department of Artificial Intelligence, Yonsei University, Seoul, South Korea · Kim Jaechul Graduate School of AI, KAIST, Daejeon, South Korea · Department of Integrative Medicine, College of Medicine, Yonsei University, Seoul, South Korea +2

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

May 12, 2026eess.IV

Physics-Grounded Adversarial Stain Augmentation with Calibrated Coverage Guarantees

Stain variation across hospitals degrades histopathology models at deployment. Existing augmentation methods perturb color spaces with arbitrary hyperparameters, lacking both a principled budget and coverage guarantees for unseen centers. We propose \textbf{C}alibrated \textbf{A}dversarial \textbf{S}tain \textbf{A}ugmentation (\textbf{CASA}), which performs adversarial augmentation in the Macenko stain parameter space with a budget calibrated from multi-center statistics via the DKW inequality. On Camelyon17-WILDS (5 seeds), CASA achieves

93.9\% \pm 1.6\%

slide-level accuracy -- outperforming HED-strong (

88.4\% \pm 7.3\%

), RandStainNA (

85.2\% \pm 6.7\%

), and ERM (

63.9\% \pm 11.3\%

) -- with the highest worst-group accuracy (

84.9\% \pm 0.9\%

) among all 10 compared methods.

Mingi Hong

434, Samseong-ro, Gangnam-gu, Seoul, Republic of Korea

Data Augmentation Healthcare Domain Generalization Histopathology Image Classification

May 11, 2026cs.CV

CellDX AI Autopilot: Agent-Guided Training and Deployment of Pathology Classifiers

Training AI models for computational pathology currently requires access to expensive whole-slide-image datasets, GPU infrastructure, deep expertise in machine learning, and substantial engineering effort. We present CellDX AI Autopilot, a platform that lets users -- from pathologists with no ML background to ML practitioners running many parallel experiments -- train, evaluate, and deploy whole-slide image classifiers through natural language interaction with an AI agent. The platform provides a structured set of agent skills that guide the user through dataset curation, automated hyperparameter tuning, multi-strategy model comparison, and human-in-the-loop deployment, all on a pre-built dataset of over 32,000 cases and 66,000 H&E-stained whole-slide images with pre-extracted features. We describe the agent skill architecture, the underlying Multiple Instance Learning (MIL) training framework supporting four classification strategies, and an iterative pairwise hyperparameter search (grid or seeded random) that reduces tuning cost by over 30x compared to exhaustive search. CellDX AI Autopilot is, to our knowledge, the first system to expose pathology-specialized agent skills and a pathology-specialized training platform to general-purpose AI agents (e.g. any LLM-based agent runtime), delivering end-to-end automated model training without requiring the agent itself to be domain-specific. The platform addresses both the ML-expertise bottleneck that limits adoption in diagnostic pathology and the engineering bottleneck that limits how many experiments a researcher can run cost-effectively.

Alexey Pchelnikov, Aleksei Pchelnikov

1HistAI

Computational Pathology Healthcare Histopathology Image Classification Automated Machine Learning Whole-Slide Image Analysis

May 6, 2026cs.CV

Geometry-Aware State Space Model: A New Paradigm for Whole-Slide Image Representation

Accurate analysis of histopathological images is critical for disease diagnosis and treatment planning. Whole-slide images (WSIs), which digitize tissue specimens at gigapixel resolution, are fundamental to this process but require aggregating thousands of patches for slide-level predictions. Multiple Instance Learning (MIL) tackles this challenge with a two-stage paradigm, decoupling tile-level embedding and slide-level prediction. However, most existing methods implicitly embed patch representations in homogeneous Euclidean spaces, overlooking the hierarchical organization and regional heterogeneity of pathological tissues. This limits current models' ability to capture global tissue architecture and fine-grained cellular morphology. To address this limitation, we introduce a hybrid hyperbolic-Euclidean representation that embeds WSI features in dual geometric spaces, enabling complementary modeling of hierarchical tissue structures and local morphological details. Building on this formulation, we develop BatMIL, a WSI classification framework that leverages both geometric spaces. To model long-range dependencies among thousands of patches, we employ a structured state space sequence model (S4) backbone that encodes patch sequences with linear computational complexity. Furthermore, to account for regional heterogeneity, we introduce a chunk-level mixture-of-experts (MoE) module that groups patches into regions and dynamically routes them to specialized subnetworks, improving representational capacity while reducing redundant computation. Extensive experiments on seven WSI datasets spanning six cancer types demonstrate that BatMIL consistently outperforms state-of-the-art MIL approaches in slide-level classification tasks. These results indicate that geometry-aware representation learning offers a promising direction for next-generation computational pathology.

Enhui Chai, Sicheng Chen, Tianyi Zhang +4

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

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

May 6, 2026cs.CV

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 \textbf{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 4, 2026eess.IV

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 4, 2026cs.CV

Validation of an AI-based end-to-end model for prostate pathology using long-term archived routine samples

Artificial intelligence (AI) is becoming a clinical tool for prostate pathology, but generalization across variations in sample preparation and preservation over prolonged time periods remains poorly understood. We evaluated GleasonAI, an end-to-end attention-based multiple instance learning model, on an independent validation cohort comprising 10,366 biopsy cores from 1,028 patients across 14 Swedish regions, using archival diagnostic specimens from the ProMort cohorts collected between 1998-2015. The model achieved an overall quadratic-weighted kappa of 0.86 for core-level ISUP grading, comparable to several experienced pathologists and consistent across geographic regions. Notably, performance remained stable across the 17-year collection period, demonstrating robustness to time-related variation in archival material, a property not consistently observed with foundation model-based approaches, with exploratory analysis demonstrating a significant prognostic gradient across AI-assigned grade groups for prostate cancer-specific mortality. These findings support the generalizability of the AI grading model and demonstrate the potential of pathology archives as a large-scale resource for AI development, validation, and retrospective prognostic research.

Xiaoyi Ji, Renata Zelic, Oskar Aspegren +11

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden · Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden · Department of Pelvic Cancer, Cancer Theme, Karolinska University Hospital, Stockholm, Sweden +8

Computational Pathology Domain Generalization Oncology Histopathology Image Classification Cross-Dataset Generalization

Apr 28, 2026cs.CV

Magnification-Invariant Image Classification via Domain Generalization and Stable Sparse Embedding Signatures

Magnification shift is a major obstacle to robust histopathology classification, because models trained on one imaging scale often generalize poorly to another. Here, we evaluated this problem on the BreaKHis dataset using a strict patient-disjoint leave-one-magnification-out protocol, comparing supervised baseline, baseline augmented with DCGAN-generated patches, and a gradient-reversal domain-general model designed to preserve discriminative information while suppressing magnification-specific variation. Across held-out magnifications, the domain-general model achieved the strongest overall discrimination and its clearest gain was observed when 200X was held out. By contrast, GAN augmentation produced inconsistent effects, improving some folds but degrading others, particularly at 400X. The domain-general model also yielded the lowest Brier score at 0.063 vs 0.089 at baseline. Sparse embedding analysis further revealed that domain-general training reduced average signature size more than three-fold (306 versus 1,074 dimensions) while preserving equivalent predictive performance (AUC: 0.967 vs 0.965; F1: 0.930 vs 0.931). It also increased cross-fold signature reproducibility from near-zero Jaccard overlap in the baseline to 0.99 between the 100X and 200X folds. These findings show that calibrated, compact, and transferable representations can be learned without added architectural complexity, with clear implications for the reliable deployment of computational pathology models across heterogeneous acquisition settings.

Ifeanyi Ezuma, Olusiji Medaiyese

Ifeanyi Ezuma, Olusiji Medaiyese

Healthcare Cross-Domain Generalization Histopathology Image Classification