Whole slide image (WSI) analysis is gaining prominence within the medical imaging field. Recent advances in pathology foundation models have shown the potential to extract powerful feature representations from WSIs for downstream tasks. However, these foundation models are usually designed for general-purpose pathology image analysis and may not be optimal for specific downstream tasks or cancer types. In this work, we present Concept Anchor-guided Task-specific Feature Enhancement (CATE), an adaptable paradigm that can boost the expressivity and discriminativeness of pathology foundation models for specific downstream tasks. Based on a set of task-specific concepts derived from the pathology vision-language model with expert-designed prompts, we introduce two interconnected modules to dynamically calibrate the generic image features extracted by foundation models for certain tasks or cancer types. Specifically, we design a Concept-guided Information Bottleneck module to enhance task-relevant characteristics by maximizing the mutual information between image features and concept anchors while suppressing superfluous information. Moreover, a Concept-Feature Interference module is proposed to utilize the similarity between calibrated features and concept anchors to further generate discriminative task-specific features. The extensive experiments on public WSI datasets demonstrate that CATE significantly enhances the performance and generalizability of MIL models. Additionally, heatmap and umap visualization results also reveal the effectiveness and interpretability of CATE.

Despite their successes in vision and language, foundation models have stumbled in pathology, revealing low accuracy, instability, and heavy computational demands. These shortcomings stem not from tuning problems but from deeper conceptual mismatches: dense embeddings cannot represent the combinatorial richness of tissue, and current architectures inherit flaws in self-supervision, patch design, and noise-fragile pretraining. Biological complexity and limited domain innovation further widen the gap. The evidence is clear--pathology requires models explicitly designed for biological images rather than adaptations of large-scale natural-image methods whose assumptions do not hold for tissue.

AI-based biomarkers can infer molecular features directly from hematoxylin & eosin (H&E) slides, yet most pathology foundation models (PFMs) rely on global patch-level embeddings and overlook cell-level morphology. We present a PFM model, JWTH (Joint-Weighted Token Hierarchy), which integrates large-scale self-supervised pretraining with cell-centric post-tuning and attention pooling to fuse local and global tokens. Across four tasks involving four biomarkers and eight cohorts, JWTH achieves up to 8.3% higher balanced accuracy and 1.2% average improvement over prior PFMs, advancing interpretable and robust AI-based biomarker detection in digital pathology.

We introduce Universal and Transferable Adversarial Perturbations (UTAP) for pathology foundation models that reveal critical vulnerabilities in their capabilities. Optimized using deep learning, UTAP comprises a fixed and weak noise pattern that, when added to a pathology image, systematically disrupts the feature representation capabilities of multiple pathology foundation models. Therefore, UTAP induces performance drops in downstream tasks that utilize foundation models, including misclassification across a wide range of unseen data distributions. In addition to compromising the model performance, we demonstrate two key features of UTAP: (1) universality: its perturbation can be applied across diverse field-of-views independent of the dataset that UTAP was developed on, and (2) transferability: its perturbation can successfully degrade the performance of various external, black-box pathology foundation models - never seen before. These two features indicate that UTAP is not a dedicated attack associated with a specific foundation model or image dataset, but rather constitutes a broad threat to various emerging pathology foundation models and their applications. We systematically evaluated UTAP across various state-of-the-art pathology foundation models on multiple datasets, causing a significant drop in their performance with visually imperceptible modifications to the input images using a fixed noise pattern. The development of these potent attacks establishes a critical, high-standard benchmark for model robustness evaluation, highlighting a need for advancing defense mechanisms and potentially providing the necessary assets for adversarial training to ensure the safe and reliable deployment of AI in pathology.

Hematoxylin and eosin-stained mitotic figure (MF) counts are essential for tumor evaluation, serving both as stan-dalone and component grades in malignancy assessment (1). Mitotic figures are broadly classified into typical and atypical variants, with atypical forms--characterized by dysregulated chromatin aggregation and reflecting ge-nomic instabilities such as chromosomal instability and aneuploidy--demonstrating independent prognostic value in cancers like breast carcinoma (2, 3). However, manual enumeration and discrimination of MF variants are time-consuming and subject to substantial inter-observer variability. To address these challenges, we present a two-stage framework for automated MF classification in the MIDOG2025 Track 2 challenge (4). First, we performed parameter-efficient fine-tuning of multiple Pathology Foundation Models (PFMs) using low-rank adaptation (LoRA) (5). Training incorporated fisheye augmentation to emphasize central mi-toses (6) and Fourier Domain Adaptation (FDA) for unsupervised style transfer with ImageNet images (7). We further enhanced domain generalization by augmenting the MI-DOG2025 set with an external labeled MF dataset (8). Second, we ensembled the adapted PFMs and ConvNeXt V2 (9) to integrate complementary morphological insights into a unified classification decision (10). Our method achieved a high balanced accuracy on validation splits and also demonstrated strong performance on the Preliminary Evaluation Phase dataset, underscoring its potential for reliable, automated MF analysis.

In digital pathology, whole-slide images (WSIs) are often difficult to handle due to their gigapixel scale, so most approaches train patch encoders via self-supervised learning (SSL) and then aggregate the patch-level embeddings via multiple instance learning (MIL) or slide encoders for downstream tasks. However, patch-level SSL may overlook complex domain-specific features that are essential for biomarker prediction, such as mutation status and molecular characteristics, as SSL methods rely only on basic augmentations selected for natural image domains on small patch-level area. Moreover, SSL methods remain less data efficient than fully supervised approaches, requiring extensive computational resources and datasets to achieve competitive performance. To address these limitations, we present EXAONE Path 2.0, a pathology foundation model that learns patch-level representations under direct slide-level supervision. Using only 37k WSIs for training, EXAONE Path 2.0 achieves state-of-the-art average performance across 10 biomarker prediction tasks, demonstrating remarkable data efficiency.

Computational pathology (CPath) has shown great potential in mining actionable insights from Whole Slide Images (WSIs). Deep Learning (DL) has been at the center of modern CPath, and while it delivers unprecedented performance, it is also known that DL may be affected by irrelevant details, such as those introduced during scanning by different commercially available scanners. This may lead to scanner bias, where the model outputs for the same tissue acquired by different scanners may vary. In turn, it hinders the trust of clinicians in CPath-based tools and their deployment in real-world clinical practices. Recent pathology Foundation Models (FMs) promise to provide better domain generalization capabilities. In this paper, we benchmark FMs using a multi-scanner dataset and show that FMs still suffer from scanner bias. Following this observation, we propose ScanGen, a contrastive loss function applied during task-specific fine-tuning that mitigates scanner bias, thereby enhancing the models' robustness to scanner variations. Our approach is applied to the Multiple Instance Learning task of Epidermal Growth Factor Receptor (EGFR) mutation prediction from H\&E-stained WSIs in lung cancer. We observe that ScanGen notably enhances the ability to generalize across scanners, while retaining or improving the performance of EGFR mutation prediction.

Biomedical Foundation Models (FMs) are rapidly transforming AI-enabled healthcare research and entering clinical validation. However, their susceptibility to learning non-biological technical features -- including variations in surgical/endoscopic techniques, laboratory procedures, and scanner hardware -- poses risks for clinical deployment. We present the first systematic investigation of pathology FM robustness to non-biological features. Our work (i) introduces measures to quantify FM robustness, (ii) demonstrates the consequences of limited robustness, and (iii) proposes a framework for FM robustification to mitigate these issues. Specifically, we developed PathoROB, a robustness benchmark with three novel metrics, including the robustness index, and four datasets covering 28 biological classes from 34 medical centers. Our experiments reveal robustness deficits across all 20 evaluated FMs, and substantial robustness differences between them. We found that non-robust FM representations can cause major diagnostic downstream errors and clinical blunders that prevent safe clinical adoption. Using more robust FMs and post-hoc robustification considerably reduced (but did not yet eliminate) the risk of such errors. This work establishes that robustness evaluation is essential for validating pathology FMs before clinical adoption and demonstrates that future FM development must integrate robustness as a core design principle. PathoROB provides a blueprint for assessing robustness across biomedical domains, guiding FM improvement efforts towards more robust, representative, and clinically deployable AI systems that prioritize biological information over technical artifacts.

With the widespread adoption of pathology foundation models in both research and clinical decision support systems, exploring their security has become a critical concern. However, despite their growing impact, the vulnerability of these models to adversarial attacks remains largely unexplored. In this work, we present the first systematic investigation into the security of pathology foundation models for whole slide image~(WSI) analysis against adversarial attacks. Specifically, we introduce the principle of \textit{local perturbation with global impact} and propose a label-free attack framework that operates without requiring access to downstream task labels. Under this attack framework, we revise four classical white-box attack methods and redefine the perturbation budget based on the characteristics of WSI. We conduct comprehensive experiments on three representative pathology foundation models across five datasets and six downstream tasks. Despite modifying only 0.1\% of patches per slide with imperceptible noise, our attack leads to downstream accuracy degradation that can reach up to 20\% in the worst cases. Furthermore, we analyze key factors that influence attack success, explore the relationship between patch-level vulnerability and semantic content, and conduct a preliminary investigation into potential defence strategies. These findings lay the groundwork for future research on the adversarial robustness and reliable deployment of pathology foundation models. Our code is publicly available at: https://github.com/Jiashuai-Liu-hmos/Attack-WSI-pathology-foundation-models.

Whole slide image (WSI) analysis is gaining prominence within the medical imaging field. Recent advances in pathology foundation models have shown the potential to extract powerful feature representations from WSIs for downstream tasks. However, these foundation models are usually designed for general-purpose pathology image analysis and may not be optimal for specific downstream tasks or cancer types. In this work, we present Concept Anchor-guided Task-specific Feature Enhancement (CATE), an adaptable paradigm that can boost the expressivity and discriminativeness of pathology foundation models for specific downstream tasks. Based on a set of task-specific concepts derived from the pathology vision-language model with expert-designed prompts, we introduce two interconnected modules to dynamically calibrate the generic image features extracted by foundation models for certain tasks or cancer types.