Histopathology Image Classification

Whole slide image (WSI) analysis in computational pathology follows a multiple instance learning (MIL) pipeline where patch embeddings are extracted independently and aggregated for slide-level prediction, but within-slide variance from staining, scanner, and local texture can overwhelm the discriminative signal. We propose Masked Feature Encoding for Multiple Instance Learning (MFE-MIL), a feature-space masking framework that trains a lightweight MLP adapter jointly with a window-based masked reconstruction branch and a MIL classification head. The two objectives are complementary. Classification guides the adapter to suppress within-slide patch variance, while window-based masked reconstruction provides an auxiliary regularizer for the adapted features without using patch coordinates, coordinate graphs, or segmentation preprocessing. The raster patch-extraction order is used only as a weak implicit prior. At inference, the decoder is removed, leaving only the adapter and MIL head. Across CAMELYON16/17, PANDA, and TCGA-BRCA with four diverse encoders, MFE-MIL improves ACC/F1 for nearly all tested aggregator-encoder settings and AUC in most, outperforms coordinate-based spatial methods (CAMIL), and achieves higher AUC than 2DMamba on three of four datasets (UNI). On five TCGA survival cohorts it improves the average concordance index for every aggregator tested, its most consistent gain. Code is available at https://github.com/AtlasAnalyticsLab/MFE-MIL.

Gastric adenocarcinoma (GA) is a leading cause of cancer-related mortality worldwide, and accurate histopathological subtype classification from whole-slide images (WSIs) is essential for effective treatment planning. While multimodal approaches that integrate pathology report text with WSIs can improve classification, existing methods often depend on computationally expensive transformer architectures and large language models. We propose a multimodal knowledge distillation (MKD) framework that combines a pretrained WSI image encoder and a clinical text encoder using Low-Rank Multimodal Fusion (LMF) to efficiently model cross-modal interactions during training. Each WSI is represented as a bag of patches paired with a slide-level diagnostic caption. The teacher model learns fused image-text representations for subtype classification, while the student model distills this knowledge to enable accurate image-only inference. We evaluate our method on the PatchGastric benchmark dataset and achieve at least 3.35% higher mean accuracy than state-of-the-art approaches, without relying on transformer-based fusion, multi-task learning, or large language models. The source code is available at https://github.com/helomelo1/MKD-LMF.

Foundation models for computational pathology are usually evaluated using AUC and accuracy, while calibration is often left untested. This matters because a model can be accurate on average but still assign overly confident probabilities to cases that are difficult even for pathologists. We study calibration across eight pathology foundation models. Using pathologist agreement as a measure of diagnostic difficulty, we find that calibration error is consistently higher on low-agreement cases than on high-agreement cases. This pattern is not apparent from aggregate expected calibration error (ECE) alone. We then propose synthetic agreement calibration, a method for improving calibration without collecting multi-annotator labels. Given a trained linear probe, we select high-confidence embeddings as class anchors and interpolate between anchors from opposite classes. The interpolation weights encode a continuous notion of diagnostic ambiguity, which we use as a synthetic agreement signal to retrain the probe with agreement-aware label smoothing. On MHIST, which includes annotations from seven pathologists, synthetic agreement calibration recovers most of the calibration improvement obtained by label smoothing based on real pathologist agreement, while substantially reducing low-agreement ECE relative to the uncalibrated baseline. Discrimination metrics are preserved. On PatchCamelyon and BreakHis, public histopathology datasets without multi-annotator labels, the method improves calibration across the evaluated foundation models, whereas annotator-dependent approaches cannot be used without additional expert annotation.

Mycosis fungoides (MF) is a rare form of cutaneous T-cell lymphoma that is often misdiagnosed in early stages due to its visual similarity to benign inflammatory dermatoses. Early and accurate diagnosis is critical for improving patient outcomes. In this paper, we propose a comprehensive diagnostic framework for automated MF detection that combines dual- scale histopathological image analysis with deep learning. To distinguish MF from other lymphoproliferative skin conditions, the proposed approach leverages a late-fusion ensemble of dual- magnification (10x and 20x) convolutional neural networks (CNNs), complemented by a random forest classifier trained on 16 clinical features. Experimental results on an expanded dataset of 6,267 images (4,306 MF; 1,961 Non-MF) across 463 patients demonstrate that strong detection performance is obtained by prioritizing higher-resolution cytological details (20x) within broader architectural context (10x). The image-based late-fusion model achieves an accuracy of 83.58% and a sensitivity of 89.13%, while the clinical random forest model achieves an accuracy of 96.6% and sensitivity of 93.8%, highlighting the po- tential of this multimodal framework as a robust clinical decision support system in dermatology. This framework addresses two distinct clinical objectives: an image-based dual-scale pipeline optimized for the early diagnostic screening of MF versus non- MF dermatoses, and a complementary clinical metadata model designed for the subsequent staging of confirmed MF cases (patch/plaque versus tumor)

Due to the gigapixel-scale nature of whole-slide images (WSIs), weakly supervised WSI analysis is commonly formulated as a multiple instance learning (MIL) problem, where patch-level features are aggregated into slide-level representations. However, diagnostic and prognostic evidence often arises from spatially coherent tumor microenvironment regions and their interactions, rather than isolated patches alone. Existing patch-level or static region-based methods usually overlook how tissue regions should be adaptively formed and subsequently evolved through microenvironment interactions across heterogeneous boundaries. In this paper, we propose Concept-Guided Tumor Microenvironment Evolution (TMEvolve), a reaction-diffusion-inspired framework that models WSIs as latent tumor microenvironment fields over discrete patch graphs. TMEvolve instantiates this view as a learnable graph-discretized evolution process over patch neighborhoods. It first forms adaptive soft tissue regions as coherent microenvironment units, then performs pseudo-time evolution through two complementary local dynamics: intra-region diffusion, which stabilizes latent states within coherent tissue compartments, and concept-guided boundary flux, which propagates visual feature signals and language-derived concept signals across heterogeneous region interfaces. The evolved microenvironment regions are finally aggregated for slide-level prediction. We evaluate TMEvolve on six datasets across three weakly supervised WSI tasks: survival prediction, gene expression prediction, and histological subtype classification. TMEvolve consistently improves over representative MIL methods, pathology foundation models, and concept-guided baselines. Ablation studies and visualizations further support the effectiveness and interpretability of TMEvolve, highlighting the value of dynamic region modeling and boundary interaction.

Background & Problem: Thyroid Fine-Needle Aspiration Biopsy (FNAB) cytology based on the Bethesda System plays a pivotal role in early thyroid cancer detection; however, deep learning approaches face substantial challenges regarding high false-negative rates and overconfidence under clinical domain shift. Methods: In this study, we propose TAM-Chain, a multi-scale (10x, 20x, 40x) thyroid cytology classification framework leveraging Absorbing Markov Chain theory combined with Shannon Entropy-based Uncertainty Quantification. The framework dynamically models multi-magnification feature extraction as an absorbing stochastic process, enabling optimal stopping criteria and a human-in-the-loop referral mechanism to strictly suppress critical diagnostic errors. Results: Extensive evaluation on an internal test set (N = 235) demonstrates a Macro F1 score of 0.9741 with an absolute False-Negative Rate (FNR) of 0.00%. On an independent external validation set (N = 1015) presenting severe domain shift, TAM-Chain maintains superior stability and classification performance (Macro F1 = 0.7026) by adaptively adjusting the expected stopping step and triggering specialist referrals, significantly outperforming single-magnification baselines. Conclusion: The TAM-Chain framework proves to be a highly effective, safe, and adaptable solution for digital pathology workflows, successfully harmonizing automated diagnostic efficiency with stringent biological safety.

Pathology foundation models (PFMs) have transformed computational pathology through powerful representation learning from histopathological images. PFMs provide rich, discriminative representations for whole slide image (WSI) analysis, enabling tasks such as slide-level classification under multiple instance learning (MIL). However, these representations may also encode non-biological signals associated with acquisition centers, potentially introducing spurious shortcuts into downstream predictions. In this work, we evaluate center-associated robustness in WSI classification using a controlled training setting with increasing class-center correlations quantified by Cramér's V. We benchmark six PFMs across four datasets and two MIL aggregators, while evaluating ComBat as a robustification strategy. We further introduce the Area Under the Cramér's V Curve (AUCC) to jointly capture absolute classification performance and its degradation as spurious correlation increases. Results show that center-related information encoded by PFMs propagates to WSI-level predictions, with robustness depending on both the PFM representation and MIL aggregation strategy. Additionally, ComBat harmonization does not provide consistent robustness gains across datasets.

Pathology vision-language foundation models vary in performance across diseases and tasks, with no single model consistently performing best. The high cost of expert pathology annotation can also limit the labeled data available for task-specific adaptation. Combining complementary pretrained representations is a potential approach to these limitations, yet learning an effective fusion from few labeled examples remains challenging. We introduce Few-shot Fusion Foundation Models of Computational Pathology (FFM-CP), which is a framework that combines multiple pathology vision-language models in the few-shot learning setting. The framework first aligns heterogeneous representations using a closed-form Orthogonal Procrustes transformation estimated from corresponding support images. This alignment preserves within-model feature geometry without training an additional alignment network. Within the aligned space, a unified graph enables information exchange across backbones by jointly refining support-image features and visual and textual class prototypes. These refined representations support complementary text-prototype and case-retrieval branches that capture semantic class knowledge and within-class visual variation, respectively. Each branch learns to combine predictions from all ordered backbone pairs, allowing queries encoded by one model to draw on evidence represented by another. We evaluate three backbone combinations on six histopathology datasets at 4, 8, and 16 shots per class. FFM-CP achieves higher mean macro-F1 than the strongest individually adapted member of each fused set in 50 of 54 comparisons. These findings suggest that combining complementary pretrained representations can improve histopathological classification when annotations are limited.

Mitotic figure (MF) analysis supports tumor grading and prognostic assessment, but automated models remain sensitive to differences in tissue type and image acquisition. We present MiTHras, a task-specific pretraining framework that combines pseudo-label-guided image- and token-level contrastive learning with masked reconstruction. We construct TCGA-MF-Pseudo, a corpus of 1.8 million cell-centered images from 14 TCGA cohorts spanning 11 organ sites. Comprehensive evaluation on MF classification, detection, count-based survival prediction, and subtype classification demonstrates the efficacy of MiTHras. It achieves the highest mean F1 on all three MF classification benchmarks and both subtype benchmarks. MiTHras also outperforms general-purpose and pathology foundation encoders by a larger margin under frozen-encoder linear probing than under full fine-tuning. Although detection gains are modest due to a shared candidate-detection stage, ablations confirm that token-level supervision improves typical-versus-atypical classification and linear probing. These findings establish that MiTHras yields robust, transferable representations for automated mitotic activity assessment.

Breast histopathology analysis increasingly relies on distributed learning because direct data pooling across institutions is often restricted by privacy, governance, and communication constraints. This study compares server-based Federated Averaging (FedAvg), fully decentralized gossip learning, and Hybrid Gossip-FedAvg for invasive ductal carcinoma (IDC) patch classification. Experiments used 277,524 color image patches with patient-disjoint training, validation, and test partitions and a workload-balanced, Dirichlet-guided allocation across six nodes. Ring, random degree-3, and fully connected gossip topologies were evaluated together with sensitivity analyses for statistical heterogeneity, mixing coefficient, learning rate, model drift, prediction disagreement, calibration, clinically motivated operating points, communication payload, and patient-level IDC burden, together with auxiliary backbone robustness analyses. In the principal alpha=0.3 experiment, Hybrid Gossip-FedAvg achieved a test area under the receiver operating characteristic curve (ROC-AUC) of 0.8811, closely followed by FedAvg at 0.8801 and fully connected gossip at 0.8751. Across three independent patient-level repetitions, FedAvg and Hybrid Gossip-FedAvg obtained the same mean ROC-AUC of 0.9082, with standard deviations of 0.0037 and 0.0043, respectively. Hybrid achieved the highest mean area under the precision-recall curve of 0.8240, whereas FedAvg produced the lowest mean Brier score of 0.1335. Denser gossip graphs improved discrimination but increased theoretical model payload, while ring gossip remained sensitive to learning rate and mixing strength. Overall, FedAvg provided the most consistently reliable server-based baseline, topology-aware gossip offered a viable decentralized alternative, and Hybrid Gossip-FedAvg provided a balanced compromise between peer-to-peer diffusion and periodic global coordination.

Early diagnosis of melanoma is critical for improving patient survival rates. However, accurately distinguishing melanoma from other skin lesions remains a significant clinical challenge due to the high visual similarity among lesion types and variability in image acquisition conditions. Artificial intelligence, particularly machine learning, has emerged as a promising tool to support dermatological diagnosis by automating feature extraction from medical images. Among the available approaches, convolutional neural networks (CNNs) have demonstrated strong performance in image classification tasks, making them well-suited for analyzing both dermatoscopic and histopathological images, given their ability to capture hierarchical visual patterns relevant to lesion characterization. Nevertheless, despite numerous pre-trained CNN architectures having been proposed, selecting the most appropriate one for a given imaging modality remains an open challenge. In this study, we evaluate pre-trained convolutional neural networks (CNNs) for skin lesion classification using dermatoscopic and histopathological image datasets. Experiments were conducted on the HAM10000, ISIC 2018, and CR-AI4SkIN datasets, evaluating the ResNet50, VGG16, VGG19, MobileNet, and InceptionV3 architectures under the same training protocol. The experimental evaluation showed that the models achieved accuracies ranging from 71% (InceptionV3 on ISIC 2018) to 84% (ResNet50 on HAM10000) on dermatoscopic images. For histopathological images, accuracies ranged from 72% (VGG19) to 83% (ResNet50) on the CR-AI4SkIN dataset. The results demonstrate that model performance differs between dermatoscopic and histopathological image modalities, showing that architectures exhibiting similar performance on dermatoscopic images exhibit different performance on histopathological data.

Pathology foundation models improve transferable representation learning for histopathology, but recent gains often rely on encoders with hundreds of millions of parameters and high inference cost. We propose TAP-Path, a task-adaptive compression framework that directly restructures a pretrained Virchow2 encoder rather than distilling it into a separate student. TAP-Path combines validation-driven transformer-block selection, physical removal of redundant blocks, input-adaptive patch-token pruning, multi-depth feature recovery, and a lightweight gated task head. The final model retains 24 of 32 transformer blocks and 70% of patch tokens after pruning, reducing encoder parameters by 24.96% (631.24M to 473.70M) and analytical encoder compute by 35.20% (340.13G to 220.40G FLOPs). Across three task-head optimization seeds, TAP-Path achieved $87.98 \pm 0.067$ test accuracy, $81.26 \pm 0.49$ balanced accuracy, and $82.38 \pm 0.48$ macro-F1 on a 32-class histopathology benchmark, compared with 86.89% for full Virchow2 and 87.67% for UNI2-h. TAP-Path achieved a Brier score of $0.1800 \pm 0.0005$ and failure-detection AUROC of $0.9047 \pm 0.0060$. A validation-only rare-aware objective improved rare-class balanced accuracy in a secondary operating analysis. Frozen external evaluation on 433 CPTAC samples yielded $91.22 \pm 0.83$ accuracy and $91.10 \pm 0.81$ balanced accuracy. These results show that task-adaptive structural and token sparsification can improve the accuracy-efficiency trade-off of large pathology foundation models while preserving reliability under internal and external evaluation.

Histopathological subtyping relies on the recognition of characteristic histological patterns. These patterns may be expressed by individual tissue structures or by the spatial distribution and co-occurrence of multiple structures, and they often span irregularly shaped tissue regions, termed semantic units in this work. However, conventional patch-based representations may fragment such units and fail to explicitly preserve their internal spatial organization, while efficiently modeling relationships among numerous spatially separated units remains challenging. To address these limitations, we propose the Semantic-Aware Subgraph State Space Model (SASG-SSM), a flexible and efficient framework for whole slide image (WSI) classification. Semantic-Aware Subgraphs (SASGs) first approximate irregularly shaped semantic units by adaptively grouping spatially connected patches guided by class-agnostic visual-semantic priors. By representing patches as graph nodes with adjacency edges, SASGs preserve their internal spatial organization rather than treating them as an unordered set. A Subgraph State Space Module (SG-SSM) subsequently combines a graph neural network encoder for intra-subgraph topology encoding with a Mamba-based state space encoder for efficient contextualization across large numbers of subgraphs. This module integrates local structural information within semantic units with global contextual information arising from their distribution and co-occurrence across the WSI, while efficiently modeling a large number of spatially distributed regions. Extensive experiments across four WSI subtyping datasets demonstrate consistent advantages over representative state-of-the-art methods. Further evaluations under small-cohort and few-shot settings demonstrate robustness and data efficiency under limited training data. Code will be released at https://github.com/HLSvois/SASG-SSM.

Clear cell renal cell carcinoma (CCRCC) grading is essential for treatment planning, yet existing approaches either analyze patch-level images directly or focus solely on nuclei-level classification, without linking to final tumor grading. We propose a semantic-guided multimodal preprocessing method that integrates nuclei classification maps from existing pre-trained models with RGB histopathology images for Vision Transformer (ViT)-based CCRCC grading. Our approach employs classification map channel concatenation and multiplicative modulation, with optimized overlays to leverage nuclei grading information, while preserving RGB textural features. Evaluation of multiple preprocessing strategies demonstrates that semantic-guided enhancement achieves 0.916 balanced accuracy, outperforming RGB-only baseline (0.707) and max-voting aggregation from prior studies (0.427). Sensitivity analysis reveals that this 21 percentage point improvement over baseline persists even under simulated perturbation at rates matching current state-of-the-art nuclei classification model error thresholds, suggesting both effective semantic utilization and practical robustness. These findings show that preprocessing-based multimodal fusion can leverage the diagnostic potential of existing imperfect nuclei classifiers, effectively bridging previously isolated fine-grained nuclear-level analysis with coarse-grained ViT-based patch classification. Per-class recall was consistent across grades (0.93, 0.91, 0.91), indicating that gains are not concentrated in the majority class. Because the sensitivity analysis perturbs ground-truth maps rather than predictions from an actual nuclei model, this result characterizes robustness under simulated error rather than deployment with a real upstream model, which remains for future work.

Histopathological whole slide images (WSIs) are central to cancer diagnosis, but their gigapixel scale, tissue heterogeneity, weak slide-level supervision, sparse diagnostic regions, and multi-scale evidence make robust automated analysis challenging. Multiple instance learning (MIL) is widely used to aggregate tile-level features into slide-level predictions, yet existing augmentation strategies often perturb tissue regions without preserving diagnostic relevance, slide context, or cross-scale structure. We propose SlideMix, a model-agnostic multimodal augmentation framework for MIL-based WSI analysis. SlideMix uses a retrieval-augmented vision-language model (VLM)-based Visual-Language Adaptive Region selector to identify diagnostically relevant regions and reduce weak-label noise. It then performs In-place Tile Shuffling within meaningful tissue regions to mix feature embeddings while preserving slide-level context. A VLM-based soft-labeling module supervises mixed samples, while a multi-factor, loss-driven online Curriculum-Learning Feedback scheme adaptively controls shuffle granularity, feature similarity, and shuffle ratio to promote cross-scale representation learning. Across 11 WSI datasets comprising 20,523 slides, 8 diagnostic tasks, and 10 WSI backbones, SlideMix improves accuracy and generalization in most settings and compares favorably with established augmentation baselines, providing a simple plug-and-play approach for more robust and scalable digital pathology models. Source code: https://github.com/Xia-Research-Lab/SlideMix

Lung cancer tissue diagnostics is complex, as therapy decisions in precision oncology rely on the integration of histomorphological, immunohistochemical, and molecular features. Yet pathological assessment remains largely visual and semi-quantitative and shows interobserver variability, while existing artificial intelligence (AI) tools cover only selected tasks, rarely reach generalizable expert-level performance, and lack prospective clinical validation. To address these challenges, we developed and clinically validated LUCAID, an agentic AI system for precision lung cancer pathology. An integrative agent couples diagnostic reasoning with nine modules that cover the full routine workflow, from quality control, tumor detection and segmentation, histological subtyping, tumor microenvironment profiling, tumor cellularity quantification, and predictive biomarker scoring (PD-L1, MET, TROP-2) to automated structured report generation. LUCAID enables users to interactively query the module outputs and generate reports that contextualize the results. Against large-scale expert ground-truth annotations, the analysis modules achieved F1 scores of 0.82-0.95. In prospective clinical validation, LUCAID reached 93.0% concordance with an expert-panel adjudicated reference standard across clinically actionable decisions, compared with 68.3-81.1% for five experienced thoracic pathologists.

High-resolution images of unprocessed surgical breast tissue can be obtained using microscopy with ultraviolet surface excitation (MUSE). This technique is considered a promising method for checking surgical margins during breast cancer surgery. In this study, MUSE images at 4x and 10x magnifications were compared using patch-level classification methods. Texture analysis (TA) based on local binary patterns (LBP) and deep learning (DL) with a base Vision Transformer (ViT) model were used. Both methods achieved similar performance at both magnifications. Using DL method, both 4x and 10x magnifications achieved 96.30% sensitivity, 100% specificity and 98.18% accuracy. Using TA method, 4x achieved better specificity (100% vs 93.33%) and 10x yielded higher sensitivity (100% vs 93.33%), but both had the same accuracy (96.67%). No clear improvement in performance was observed with 10x magnification. These results show that 4x imaging achieves the same diagnostic accuracy as 10x imaging. At the same time, 4x offers a larger field of view and faster image capture. Therefore, lower magnification can be effectively used in MUSE systems for accurate and efficient intraoperative margin assessment.

Whole slide images (WSIs) in digital histopathology are acquired at discrete magnification levels encoding complementary diagnostic information from global tissue architecture to fine-grained cellular morphology. Yet, deep learning models remain sensitive to scale variation. Existing magnification-invariant methods rely on multi-scale architectures at predefined discrete resolutions, while in clinical deployment the acquisition magnification varies continuously, rarely aligns with a model's fixed training resolution, and intermediate scales are common, so robust coverage otherwise demands a costly ensemble of magnification-specific models. We propose Conditional Layer Normalization (CLN), a lightweight mechanism that generates affine normalization parameters from input pixel size via a small MLP, integrated into standard CNN architectures for both WSI classification and segmentation. Trained on patches sampled continuously across a range of pixel sizes, the model decouples inference from scanner-dependent magnification and generalizes to arbitrary, previously unseen scales at test time. On the PANDA prostate cancer dataset, our approach on average matches or exceeds independently trained single-magnification models and ranks among the top three performers at every evaluated magnification, including those unseen during training. This collapses a five-model ensemble into a single network and reduces training, and inference cost roughly 4-5 times, while leaving the multiply-accumulate count unchanged. The code is available at: https://github.com/aflorkowska/OneModelToMagnifyThemAll.

Transformer models are increasingly used for whole-slide image analysis in computational pathology. Yet, WSIs differ fundamentally from natural images: neighbouring patches often contain highly similar tissue type, stain, texture, and cellular composition. We identify this local spatial redundancy as a pathology-specific failure mode of self-attention, where dominant neighbourhood features can be repeatedly mixed into patch-tokens and weaken subtle diagnostic or prognostic deviations. We propose Gated Spatial Redundancy Projection (Gated SRP), a lightweight drop-in correction module for self-attention layers. For each patch token and attention head, Gated SRP estimates a local redundancy axis from neighbouring value vectors, projects the attention output onto this axis, and applies a learned signed gate to correct the redundancy-aligned component geometrically. Across five TCGA survival cohorts, Gated SRP obtains the highest mean C-index among the compared attention variants in all cohorts, with an average improvement over the base attention, while adding only +0.02% parameters. Across five slide-level classification datasets, it improves the base attention on 12 of 16 reported metrics and achieves the best AUC on three datasets. Code is publicly available at https://github.com/AtlasAnalyticsLab/GatedSRP.

Spatial mapping of lung adenocarcinoma (LUAD) growth patterns across whole slide images (WSIs) requires resolving architectural context at the region level, yet existing methods operate at the individual tile level and produce generic morphological clusters rather than clinically defined pattern maps. We propose a weakly supervised Bag-of-Visual-Words (BoVW) pipeline that learns a visual vocabulary from frozen foundation model embeddings extracted from a small set of annotated regions of interest (ROIs). Pattern prototypes are constructed as mean BoVW histograms of same-label ROIs and used for nearest-prototype classification of sliding-window regions under Jensen--Shannon divergence. The resulting predictions are projected onto the WSI tile grid to produce interpretable spatial pattern maps. We evaluate the method on 87 CPTAC-LUAD patients using three foundation model encoders and multiple vocabulary sizes on two clinically motivated tasks. For tumour/healthy classification, the best configuration achieves a balanced accuracy of $0.974$ with H-Optimus-1, approaching the $0.987$ obtained by a supervised SVM trained on mean-pooled WSI embeddings. For binary histologic grade classification, the BoVW pipeline achieves higher balanced accuracy than the supervised baseline for all encoders, suggesting that ROI-level pattern decomposition preserves grade-relevant heterogeneity that is attenuated by global mean pooling.

Vision Transformers (ViTs) and their hierarchical variants have achieved strong performance in Computational Pathology (CPath). However, most are pre-trained on single-resolution Whole Slide Images (WSIs), limiting their generalization across arbitrary resolutions. Gigapixel WSIs inherently contain diagnostic patterns at multiple scales, including cellular morphologies, tissue architectures, and global context, mirroring how expert pathologists examine WSIs. We introduce Multi-Resolution Pyramid Transformer (MRPT), a model that hierarchically aggregates multi-resolution information from cellular to tissue and WSI levels. MRPT employs a biologically meaningful Consecutive Cross-Resolution Attention (CCRA) mechanism to capture scale-independent interactions and enforces multi-resolution semantic consistency by aligning embeddings across resolutions, yielding robust and generalizable WSI representations. Pre-trained in a multi-resolution self-supervised manner on 624M patches, 2.4M regions, and 36K WSIs, MRPT learns rich coarse-to-fine histopathology features. Extensive experiments on 34 diverse datasets show that MRPT surpasses recent foundation models and Multimodal Large Language Models (MLLMs) in cancer subtype classification, tissue phenotyping, and Visual Question Answering (VQA) for WSI understanding.

Breast core needle biopsy (CNB) is central to breast cancer diagnosis yet remains challenging because limited tissue sampling, lesion heterogeneity, and subtle morphologic overlap can obscure subtype distinctions. We developed CorePath, a breast-specialized multimodal pathology foundation model fine-tuned from PRISM using 7901 paired CNB whole-slide images and diagnostic reports from two centers. Evaluated across six CNB cohorts and two public breast pathology benchmarks without task-specific retraining, CorePath consistently outperformed PRISM across cancer detection, invasion assessment, and histological subtyping. It achieved weighted area under the receiver operating characteristic curves (AUCs) of 0.9526-0.9735 for five-class CNB histological subtyping across private centers. On public benchmarks, CorePath outperformed leading pathology foundation models, achieving the highest weighted AUCs of 0.7780 for BCNB invasive carcinoma subtyping, 0.8178 for BRACS lesion stratification, and 0.8252 for BRACS fine-grained classification. In report generation, CorePath reduced the overall non-breast hallucinations from 30.1% to 2.8%, demonstrating improved domain fidelity after breast-specific adaptation. CorePath-CRG further combined conformal filtering of subtype and binary cancer status predictions with Learn-Then-Test-based threshold calibration to support selective narrative release, diagnostic fallback, and deferral. CorePath-CRG achieved zero non-breast hallucinations among released outputs and showed the strongest overall performance in pathologist-validated LLM-based Evaluation Scores and quantitative report-generation metrics across most centers. These results demonstrate that domain-specialized foundation models with statistical risk control offer a promising approach for accurate breast CNB diagnosis and reliable report generation.

Whole slide image (WSI) classification is an evidence-driven task, where diagnostic cues are often sparse, spatially organized, and class-dependent. Existing MIL and vision-language methods aggregate a large pool of patch features into a single global slide representation. Under few-shot supervision, limited slide-level labels make it difficult to learn a reliable aggregation mechanism that organizes sparse local cues into compact and coherent diagnostic evidence. Moreover, a shared slide representation compresses evidence supporting a candidate class and its alternatives into the same feature, limiting class-specific reasoning and interpretability. To address these issues, we propose EviBall, a class-conditioned evidence retrieval framework for few-shot WSI classification. EviBall organizes local patches into Evidence Balls through semantic-spatial assignment and center refinement, yielding compact and spatially coherent evidence units under weak supervision. It then uses task-specific class queries, including language-guided queries for morphology-oriented tasks and molecular-guided queries for molecular endpoint prediction, to retrieve supporting evidence balls and produce class-conditioned evidence representations for direct class-wise prediction. By introducing structured evidence units and task-relevant semantic guidance, EviBall reduces the reliance on learning an unconstrained global aggregation mechanism from scarce slide-level labels. It therefore reformulates few-shot WSI classification as structured evidence retrieval and competition among candidate classes. Extensive experiments across four morphology-oriented and molecular endpoint WSI tasks demonstrate that EviBall consistently outperforms conventional and vision-language MIL baselines under diverse few-shot settings, while providing spatially localized and class-specific evidence for each prediction.

Understanding tissue organisation in multiplexed imaging requires modelling both cellular phenotypes and their spatial context. Existing approaches typically rely on handcrafted features, such as marker intensity statistics or cell-type proportions, which often fail to scale or generalise across cohorts with heterogeneous marker panels. We introduce MUL-T, a lightweight transformer framework that reframes tissue architecture as a masked contextual prediction task over discrete cell tokens. By learning contextualised [CLS] embeddings without task-specific supervision, the model captures higher-order cellular interactions while remaining computationally efficient. We evaluate MUL-T on several clinically relevant downstream tasks, including core-level tumour pattern classification, patient-level grading, PD-L1 positivity prediction, and cross-dataset treatment response prediction. Across tasks, MUL-T consistently outperforms classical feature-based baselines and achieves performance comparable to a foundation ViT model, despite substantially fewer parameters and lower training cost.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths globally, with approximately 1,926,425 new cases and 904,019 deaths reported in 2022. Accurate histologic grading plays a critical role in prognosis and treatment planning for colorectal adenocarcinoma. In recent years, artificial intelligence and its subcategories, including machine learning and deep learning, have been increasingly employed for automated cancer detection and classification. An appropriate and well-organized dataset is the essential first step to achieve this goal. This paper introduces CRC-HGD, a histopathological microscopy image dataset of 1,914 images obtained from 214 colorectal adenocarcinoma patients (Grade I: 106, Grade II: 75, Grade III: 33). The specimens are H&E-stained colorectal tissue sections acquired at the Poursina Hakim Research Center of Isfahan University of Medical Sciences, Iran, diagnosed between 2014 and 2019, and graded according to the World Health Organization (WHO) criteria into three grades: well-differentiated (Grade I), moderately differentiated (Grade II), and poorly differentiated (Grade III). For each specimen, four magnification levels are provided: 4x, 10x, 20x, and 40x. The dataset is accessible via Mendeley Data (https://doi.org/10.17632/yfp5sfj47m.4) and at http://databiox.com, where the latest version is also available. The distinctive feature of this dataset is the provision of labeled specimens across all three differentiation grades at multiple magnification levels, enabling comprehensive computational analysis of colorectal cancer grading.

Causal inference using front door intervention and multi-instance learning (MIL) has advanced the analysis of Whole Slide Images (WSI) in digital pathology. These methods adjust feature distributions of subtle evidence sub-images to correctly associate them with WSI-level diagnoses. We propose and prove 2 hypotheses for evaluating such methods: 1) Causal inference MIL introduces an independent classification channel that effectively completes WSI classification; 2) Greater difference between features extracted by the new and baseline channels increases effectiveness in eliminating false correlations. This hypothesis describes the core of causal inference MILs: overlaying parallel, independent channels to eliminate false associations between WSI-level diagnostic and non-diagnostic evidence sub-images by increasing deep feature diversity. Based on these hypotheses, we evaluated several causal inference MILs on breast cancer and non-small cell lung cancer datasets. This hypothesis provides a new theoretical perspective for applying causal inference to WSI analysis.

Self-supervised learning (SSL) has emerged as an effective paradigm for learning transferable representations from large-scale unlabeled whole slide images (WSIs). However, existing SSL methods primarily learn generic visual features and often fail to explicitly capture pathology-specific morphological patterns that are critical for disease characterization. To address this limitation, we propose Tiny Vision Transformer with Pathology-Aware Prototype Distillation (TVT-PAPD). This self-supervised pathology representation learning framework integrates a Tiny Vision Transformer (TVT) with a novel Pathology-Aware Prototype Distillation (PAPD) module. PAPD employs a learnable pathology prototype bank to discover and preserve representative tissue morphology patterns, encouraging semantically similar pathological regions to learn consistent and discriminative representations. The proposed framework enhances pathology-aware feature learning while maintaining computational efficiency with 90M parameters. Experiments on the Cancer Genome Atlas (TCGA) low-grade glioma (LGG)/glioblastoma (GBM) dataset and the Indian Pathology Brain (IPD-Brain) dataset demonstrate that TVT-PAPD achieves weighted F1-scores of 93.02% and 90.23%, respectively, for LGG-GBM classification, while exhibiting strong cross-cohort generalization across independent glioma datasets.

Whole slide images (WSIs) provide rich diagnostic information for computational pathology, but their gigapixel scale, stain variation, scanner differences, tissue artifacts, and limited expert annotation make robust model training challenging. This paper presents a multi-source Masked Autoencoder (MAE) framework, named ProsMAE, for histopathology representation learning. Tiles from Prostate cANcer graDe Assessment (PANDA), CAncer MEtastases in LYmph nOdes challeNge 2017 (CAMELYON17), and BReAst Carcinoma Subtyping (BRACS) are used for ProsMAE pretraining to expose the encoder to diverse tissue morphology and acquisition conditions. The learned encoder is transferred for International Society of Urological Pathology (ISUP) grade classification through ProsCLS, using a frozen encoder and a linear classification head. ProsMAE achieved a higher mean validation quadratic weighted kappa (QWK) than the vanilla MAE frozen linear-probe baseline under the evaluated disjoint PANDA split. Repeated-split evaluation remains necessary to further establish robustness across split compositions.

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.

Model merging offers a practical alternative to conventional continual learning by integrating independently fine-tuned models without retaining previous training data. Recent state-of-the-art model merging methods employ test-time adaptation (TTA-guided merging) to address distribution shifts by adjusting merging-related variables using unlabeled target data. However, these methods have primarily been studied in multi-task or single-target settings, and their behavior under sequential continual learning remains insufficiently understood. We present a benchmark study that maps this family of methods to rehearsal-free continual Whole Slide Image classification and evaluates them against traditional continual-learning approaches. Experiments on six TCGA cancer-subtyping cohorts cover CLASS-IL and TASK-IL scenarios, in-domain and out-of-domain evaluation, and different task orders. The results show that adapting model merging at test time can provide strong task-specific performance and improve retention of previously acquired knowledge without storing historical WSIs. Nevertheless, performance remains sensitive to task order and to the interaction between adaptation on the current distribution and accumulated knowledge. This benchmark identifies model merging with test-time adaptation as a promising direction for continual computational pathology and motivates future methods that balance adaptation to domain shift with explicit preservation of historical knowledge.