Pathology

High-risk non-muscle-invasive bladder cancer (HR-NMIBC) carries substantial risks of recurrence and progression, while current clinical risk stratification remains limited. CHIMERA was established as a multimodal AI challenge to benchmark prediction in HR-NMIBC under standardized evaluation. Task BRS predicts RNA-seq-defined BCG Response Subtypes from histopathology and structured clinicopathological data, whereas Task Progression models time-to-progression using histopathology, structured data, and RNA sequencing. A multimodal dataset of 368 patients was divided into public training and hidden validation and test sets. In total, 159 submissions were made, and 13 top-performing models were selected for benchmarking. The best models achieved a weighted F1 score of 0.73 for Task BRS and a C-index of 0.68 for Task Progression. Post-challenge analyses revealed task-dependent modality contributions, cohort-dependent performance degradation, and sensitivity to missing structured data. In Task BRS, histopathology partly compensated for pathology-derived structured variables, whereas progression models showed greater dependence on complementary inputs. Cross-model error analysis further identified patients that were consistently difficult across different architectures, with T1 substage associated with prediction difficulty. These findings highlight barriers to transportability and the importance of missingness-aware modeling and independent multi-institutional validation. CHIMERA provides a standardized multimodal benchmark for bladder cancer and a framework for studying not only model performance, but also robustness, information sufficiency, and patient-level prediction failure.

Whole-slide images (WSIs) are challenging for vision-language reasoning because diagnostically relevant morphology is sparse, heterogeneous, and distributed across gigapixel-scale images and multiple spatial resolutions. Existing WSI models and pathology agents can aggregate slide features or actively acquire evidence, but the information retained after exploration is often difficult to access semantically while preserving its connection to the original visual evidence. We introduce SlideBank, a training-free framework that represents each WSI as a persistent, concept-indexed, and spatially grounded evidence bank. SlideBank performs question-independent coarse-to-fine exploration to identify informative regions and multi-scale views, converts them into explicit morphological observations, and grounds pathology signals to their supporting patches and WSI coordinates. At inference time, questions are routed to relevant signals and evidence scales, and the linked global, regional, and patch evidence is integrated through confidence-based cross-level consensus. Experiments on WSI-VQA and SlideBench-BCNB show that with Patho-R1, SlideBank reaches 52.77% on WSI-VQA and with Quilt-LLaVA, it reaches 50.92% average accuracy on SlideBench-BCNB, while structured signal-guided retrieval consistently outperforms random evidence sampling. Reusing the same bank across repeated queries further achieves over 99% rephrasing consistency and substantially reduces amortized inference cost through persistent evidence reuse.

Safe deployment of AI methods in medicine requires robust guardrails that detect when input data deviate from the training distribution to ensure that models provide predictions only within their scope of expertise and abstain otherwise. Out-of-distribution (OOD) detection can provide such safeguards and is extensively studied in general computer vision. Yet, it remains underdeveloped in computational pathology, where gigapixel whole-slide images (WSIs), subtle differences between disease subtypes, and variability in tissue preparation pose unique challenges for conventional OOD methods. We propose ZIO, a training-free, multimodal OOD detector for pathology WSIs that leverages vision--language pathology foundation models (FMs). ZIO constructs text and visual prototypes of in-distribution classes and integrates their complementary information through a prototype shrinkage mechanism to derive OOD scores. We provide the ZIO formulation for both slide- and patch-level FMs. We evaluate ZIO across diverse clinically relevant domain shifts, including rare diseases and near-OOD settings. Extensive evaluation of over 14,700 WSIs from five independent consortia shows that ZIO consistently outperforms both unimodal prototypes and 40 state-of-the-art OOD methods. These results demonstrate the benefits of multimodal representation for OOD detection and pave the way towards safer AI deployment in clinical practice.

Pathology foundation models (PFMs) provide strong tile-level representations via self-supervised pre-training on large-scale pathology images. Yet, PFMs are developed under diverse and often opaque data, architecture, and objective choices, inducing latent representational biases that limit robustness and obscure what each model specialises in. We present AdaFusion, a lightweight adaptive fusion framework that integrates complementary signals from multiple frozen PFMs through (1) low-dimensional feature compression and (2) a sample-conditioned gating module that reweights model-wise (and optionally channel-wise) contributions. Beyond improving predictive accuracy, AdaFusion provides contribution-driven interpretation that offers evidence consistent with model-specific preferences and synergistic interactions across tissue phenotypes. We evaluate AdaFusion on three public benchmarks spanning treatment response prediction, prostate cancer grading, and spatial gene expression inference. AdaFusion consistently outperforms individual PFMs and other fusion baselines, while providing interpretable tissue visualisation which aligns model preferences with morphological patterns. Code is available at: https://github.com/xyx-98/PathoOracle.

Pathology foundation models (PFMs) provide strong tissue representations and have become central to digital pathology. However, deployment in disease-specific settings is limited by 1) the high computational cost of billion-parameter PFMs and 2) distribution mismatch and non-biological bias inherited from pan-cancer, multi-centre pre-training, including site-specific signatures and imbalanced disease prevalence. These factors can encourage shortcut learning and under-emphasise subtle morphology required for reliable modelling of a specific cancer type. We present SmartStu (a Smart Student), a framework to customise compact, breast-cancer-specific PFMs via distillation whilst mitigating confounding. SmartStu distils representations from multiple teacher PFMs into a lightweight student backbone. Crucially, we introduce adversarial distillation that leverages a dedicated noise model trained to predict nuisance, edge-dominated cues on the distillation set. Using this noise model as a counterexample, the adversarial objective encourages the student to recognise, yet suppress, features predictive of nuisance targets. We further incorporate multi-teacher ensemble distillation and an auxiliary self-supervised objective with artefact injection. We validate SmartStu on three external cohorts (Yale HER2, SLN-Breast, and BRACS) with multiple tiny backbones. SmartStu yields breast-cancer-specific PFMs that are over $30\times$ smaller than general PFMs whilst largely preserving, and sometimes improving, downstream performance measured by balanced accuracy (bAcc) and AUC. Code is available at https://github.com/zwchen03/advDistall.

Recent radiology-adapted vision-language models have achieved strong performance on standard report generation benchmarks, yet their robustness and generalization remain constrained by imperfect alignment and correlation between visual and textual features. Existing methods connect image and text either implicitly through autoregressive report supervision or explicitly through contrastive learning. However, autoregressive supervision alone is insufficient to establish reliable image-text alignment, while contrastive learning can push apart unpaired reports that describe related pathologies simply because they are not paired with the same image. This is problematic in radiology, where different reports may share compatible pathology semantics rather than being true negatives. As a result, the learned representation may fail to organize images and reports around shared pathology concepts, causing the decoder to rely on pretrained language priors and generate clinically plausible reports that are not fully supported by radiographic evidence. To address this issue, we propose PALM, a pathology-aware alignment framework for radiology report generation. Instead of directly matching each image-report pair while separating all others, PALM aligns visual and textual features through shared pathology prototypes. These prototypes provide a clinically meaningful bridge between radiographic evidence and textual findings, allowing cases with similar pathology semantics to move toward common concepts without separating compatible cases. In addition, we introduce Masked Evidence Modeling to strengthen the image encoder sensitivity to local radiographic evidence by learning semantic changes caused by masked image regions. Experiments on MIMIC-CXR, IU X-Ray, and MIMIC-ABN show that PALM consistently improves both report generation and abnormality-focused robustness.

Acoustic biomarkers show promise for detecting Alzheimer's Disease (AD), yet whether the cues driving diagnostic AI align with those salient to human listeners is underexplored across languages and genders, where pathological markers and perceptual strategies differ. We train models to predict clinical AD status (pathology) and human perceptual scores across Mandarin and Greek, male and female speakers. Using SHAP for interpretability and statistical models for validation, we compare feature importance by subgroup. Results reveal a context-dependent divergence: pathological-perceptual alignment is significant for Mandarin and female speakers but disappears for Greek and male speakers, where pathology models did not exceed chance; this is a failure mode that population-specific auditing surfaces. Global Explainable AI (XAI) explanations can mask critical demographic divergences, highlighting the need for population-specific explainability auditing for equitable deployment of clinical speech AI.

Pathological diagnosis is inherently multi-scale, requiring the integration of global tissue architecture at low magnification with cellular morphology at higher magnification. However, existing pathology benchmarks and vision-language models (VLMs) are still largely developed under single-scale settings, limiting their ability to learn clinically meaningful multi-magnification reasoning. Moreover, naively constructed visual question answering (VQA) tasks may be susceptible to text-only or superficial visual shortcuts, leading to unreliable assessments of visual understanding. To address these limitations, we introduce a benchmark and training framework for shortcut-resistant cross-scale pathology reasoning. We design an Adversarial Text-only Screening strategy for semantic reasoning questions and a Structure-controlled Distractor Sampling strategy for visual grounding questions, encouraging models to rely on cross-scale visual evidence. Based on this pipeline, we construct PathScale-VQA, a high-quality cross-scale pathology VQA benchmark with 10,373 multiple-choice questions grounded in 1,368 diagnostic paths across multiple magnification levels. Building on the semantic reasoning set, PathScale-R1 is optimized through Difficulty-driven Reasoning Distillation supervised fine-tuning followed by reinforcement learning with a Scale-aware Reasoning Structure reward, which encourages the use of evidence across magnifications. Extensive experiments demonstrate state-of-the-art performance of PathScale-R1 on cross-scale reasoning tasks and effective transfer to conventional single-scale pathology VQA. Our code is available at https://github.com/iMVR-PL/PathScale-R1.

Pathology vision-language models (VLMs) have recently progressed rapidly and are commonly evaluated by answer accuracy on pathology VQA benchmarks. However, we dig into current evaluations and identify three overlooked issues: 1) Visual evidence is not always necessary. For instance, Gemini-3-Pro achieves 53.5% average accuracy across 5 VQA benchmarks without any visual input. 2) Domain training can improve accuracy without proportional gains in visual binding. Compared with Qwen2.5-VL-7B, Patho-R1-7B exhibits a 5.8-point lower multimodal gain and a 3.7-point lower attention IoU. 3) Entity-level attention is diffuse and weakly query-specific. On PathVG, attention maps remain highly correlated across different entity queries. These issues can lead to substantial misjudgments of pathology VLMs' actual multimodal capabilities. To this end, we present PathBind, a benchmark comprising 2,600 samples: PathBind-VQA with 1,500 questions across six dimensions, PathBind-PTA with 600 questions from a private pathology teaching atlas, and PathBind-Grounding with 500 expert-curated region-level samples. Each component undergoes task-specific automated filtering and expert review to reduce textual shortcuts and improve entity-region correspondence. We evaluate 18 representative VLMs on VQA samples of PathBind and five existing pathology VQA benchmarks, and further evaluate 10 VLMs on PathBind-Grounding and PathVG. Results show that current pathology VLMs still exhibit a substantial gap between answer-side performance and visual-semantic binding.

Whole-slide image (WSI) diagnosis requires identifying diagnostically relevant regions, examining them across magnifications, and integrating multi-scale evidence. However, most existing pathology benchmarks evaluate models on pre-cropped patches or pre-extracted slide features, leaving their ability to acquire evidence directly from gigapixel WSIs largely untested. We introduce PathAgentBench, a benchmark for evaluating evidence-seeking vision-language models (VLMs) across four complementary capabilities: image-to-text matching for evidence interpretation, text-to-image retrieval for evidence verification, diagnostic-region localization for evidence acquisition, and multi-scale reasoning for evidence integration. The benchmark is organized as a diagnostic tree that links nested regions across magnifications with scale-specific findings and path-level diagnoses. It contains 1,822 TCGA WSIs and 17,135 diagnostic paths annotated by ten board-certified pathologists. An additional private cohort of 190 breast cancer WSIs with detailed annotations is used to evaluate autonomous whole-slide exploration. We evaluate 20 general-purpose, medical, and pathology-specialized models. Leading open-weight models achieve over 93% accuracy in multi-scale reasoning and over 50% accuracy in both cross-modal matching tasks. In contrast, diagnostic-region localization remains challenging: the best text-guided mean intersection-over-union is below 0.09, underperforming a simple center-based heuristic. During autonomous exploration, the unconditional hit rate decreases from 0.522 at low magnification to 0.185 at intermediate magnification and 0.020 at high magnification. These results reveal a pronounced gap between reasoning over curated evidence and acquiring that evidence directly from WSIs. PathAgentBench provides a unified framework for measuring and improving evidence-seeking pathology models.

On-policy distillation (OPD) has become a key paradigm in LLM post-training, yet its training dynamics remain poorly understood. We present a systematic study examining the role, pathologies, and regulations of OPD. We first clarify the role of OPD as an exploration catalyst: it steers the student toward correct reasoning paths via dense token-level guidance, without expanding capability ceiling. We confirm this by showing that prompt diversity matters more than per-problem sampling numbers, and critically, that the effectiveness of OPD hinges entirely on the quality of its guiding signal. This dependency exposes two pathologies that derail exploration. The Student-Teacher Mismatch occurs when a large teacher-student distributional gap causes the guiding signal to misalign with task correctness, steering exploration in counterproductive directions. Length Exploitation arises when the aggregated token-level objective creates length-dependent shortcuts, allowing the student to game the reward landscape through response truncation or redundant padding, exploring degenerate length modes rather than reasoning strategies. To tame these pathologies, we investigate lightweight signal regulations: advantage clipping and log-scale compression, ensuring exploration is guided by faithful signals. Experiments across seven benchmarks demonstrate that these regulations alleviate length exploitation and enable effective distillation, stably surpassing OPD variants and RLVR baselines, thereby confirming that well-regulated signal quality, rather than mere teacher scale, governs successful exploration in OPD.

Uterine diseases represent an important category of gynecologic pathology and require accurate histopathological assessment for diagnosis and treatment planning. Whole-slide images (WSI) have enabled the digital transformation of pathology workflows and provided new opportunities for artificial intelligence (AI) in computational pathology. In particular, multimodal models that jointly analyze histopathology images and pathology reports have shown promising potential for automated pathology report generation and AI-assisted diagnosis. However, the development of such systems remains limited by the scarcity of datasets that pair whole-slide images with clinically meaningful pathology reports. Instead, existing pathology datasets focus on patch- or slide-level annotations of a single endpoint (e.g., disease class), which do not fully capture the rich information in full clinical diagnostic workflow reports. Here, we introduce TUM-Uteria, a uterine pathology dataset comprising WSIs paired with diagnostic pathology reports at both the case and slide levels, collected from a tertiary medical center. The dataset contains 216 clinical cases, comprising 455 slide-level WSI-report pairs. The dataset underwent a structured multi-stage validation procedure involving board-certified pathologists to ensure reliable annotations. TUM-Uteria supports research in computational pathology, including whole-slide image analysis, multimodal learning, and automated pathology report generation.

Autonomous computational pathology (ACP) converts high-level pathology analysis goals into executable, traceable and clinically bounded workflows. Realizing this capability requires adapting general agentic harness systems to pathology-specific tasks, tools, evidence standards and clinical claim boundaries. We contribute ACP-Bench, a framework that adapts existing harness systems from computational pathology support toward ACP workflow capability. ACP-Bench evaluates 41 pathology workflow tasks, including 24 biomarker, 7 morphology and 10 prognosis tasks spanning 6 body-system groups and 9 endpoint families. The benchmark evaluates 9 models and 3 harness groups (Claude Code, Codex and Open Code), yielding 369 complete trajectories. ACP-Bench evaluates each trajectory across workflow execution, diagnostic performance and clinical-boundary alignment, combining expert-adjudicated process audits, diagnostic assessment and pathologist-validated safety review. Across evaluated systems, workflow initiation, task interpretation and diagnostic reporting were more mature than tool-bound execution, result binding and reflective workflow revision, and formal end-to-end completion remained rare. ACP-Bench provides a reusable standard for auditing whether agentic systems can operationalize pathology workflows before claims of reliable clinical autonomy.

Gastric intestinal metaplasia (GIM) is a precursor lesion to gastric dysplasia and adenocarcinoma whose early detection is crucial for intervening in the carcinogenesis cascade. Artificial intelligence (AI) holds considerable promise for real-time endoscopic detection and characterization of GIM. However, development of reliable AI models has been constrained by the absence of publicly available, histopathologically validated datasets that combine detailed endoscopic annotations, histological subtype (complete and incomplete), standardized grading systems, and normal mucosal patterns. GIM-ENDO was designed to fill this gap. The dataset comprises demographic data, endoscopic findings, histopathological results, and H. pylori status acquired using the Olympus EVIS X1 system with white-light endoscopy (WLE) and image-enhanced endoscopy (IEE), including narrow-band imaging (NBI) and magnifying NBI (M-NBI), along with images and video clips from 24 patients (22 GIM-positive, 2 normal controls). Annotations cover six primary IEE endoscopic signs -- light blue crest (LBC), marginal turbid band (MTB), white opaque substance (WOS), TV pattern (Fusion), atrophy, and map-like erythema (MLE) -- plus two additional endoscopic findings (AHP and GA) recorded where present. GIM subtypes (complete and incomplete) are annotated for all GIM-positive cases; OLGA and OLGIM staging are provided where complete histological sampling was available. The dataset is publicly accessible at https://doi.org/10.5281/zenodo.20707267. For the latest updates and further information regarding this dataset, readers are referred to the DataBioX website: https://databiox.com A short version of this work has been submitted to MICCAI 2026 Open Data Track.

Computational pathology has advanced rapidly with the emergence of foundation models, yet widespread adoption remains limited by substantial technical complexity and programming requirements. Here we present PathLab, an autonomous agentic framework that translates natural-language research objectives into executable and validated computational pathology workflows through the structured composition of domain-specific skills and tools. By organizing workflow generation around reusable methodological modules, including data preprocessing, model development, evaluation and interpretation, PathLab enables studies to be specified at the level of scientific intent rather than implementation details. We evaluated PathLab across 12 public datasets spanning four representative task families: region-of-interest classification, whole-slide image classification, segmentation and survival prediction. Across all task categories, PathLab achieved non-inferior performance relative to expert implementations, while consistently enforcing semantic validity of user prompts and proactively rejecting incompatible workflow specifications prior to execution. In controlled user studies, PathLab substantially reduced the time required to generate executable analytical pipelines and enabled domain experts without programming experience to independently design, execute and evaluate computational pathology studies. Together, these results establish PathLab as a reliable interface between biomedical intent and computational execution, enabling computational pathology studies to be designed at the level of scientific questions rather than programming expertise. By lowering technical barriers to advanced AI methodologies, PathLab provides a foundation for the broader democratization of computational 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.

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

Deep neural networks trained under severe class imbalance often exhibit degraded performance, typically attributed to statistical bias. In this work, we identify a complementary optimization-level pathology: inter-class gradient interference within shared representations, where gradients from majority classes suppress minority-class learning. To analyze this phenomenon, we introduce a diagnostic framework based on layer-wise gradient flow analysis and a Gradient Conflict Matrix, which quantifies interference using cosine similarity between class-specific gradients. Using this framework, we study multi-branch convolutional architectures and propose a lightweight modification, Class-Specific Branch Attention (CSBA), that enables branch-specific channel reweighting to reduce gradient coupling. This mechanism promotes implicit feature decoupling across branches while preserving architectural simplicity. Empirically, CSBA improves minority-class performance, increasing the F1 score for the Physical-Damage class from 0.261 to 0.522 under severe imbalance, while maintaining comparable overall accuracy. Validation on CIFAR-10-LT confirms that this behavior generalizes across imbalanced visual recognition settings, with Macro-F1 improving from 0.595 to 0.655. More broadly, our findings highlight the importance of considering optimization dynamics alongside statistical methods when designing architectures for imbalanced learning.

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.

Data scarcity in multimodal pathology motivates unified generative models that synthesize modality-specific appearance while preserving anatomically coherent structure. Although modalities differ in appearance statistics, morphological structures such as cellular topology and tissue boundaries are largely preserved across acquisition protocols. However, existing methods often model these factors within a homogeneous token stream, implicitly coupling structure with appearance and weakening structural controllability under modality shifts. To address this, we propose pathology Autorgressive modeling (PathAR), a structure-first autoregressive synthesis framework that explicitly factorizes structure and appearance for modality-label-conditioned pathology generation.PathAR employs a dual vector quantization (Dual-VQ) tokenizer to decompose samples into mask-grounded structure and appearance tokens, and an interleaved autoregressive (IAR) transformer with asymmetric attention visibility to enforce structure-to-appearance dependence. PathAR stabilizes morphology under heterogeneous modality-specific appearances and enables spatially aligned image--mask pair generation. Extensive experiments show that PathAR improves structural consistency and modality fidelity over baselines, maintains sample diversity, supports downstream segmentation in data-scarce regimes, and demonstrates extensibility to finer-grained intra-modality organ-label variation.

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

Distilling demonstration effects into hidden-space interventions offers a lightweight alternative to full finetuning. However, existing multimodal variants are mostly evaluated on short-form tasks, where outputs end after a few tokens. Extending these methods to long-form generation exposes a fundamental yet underexamined limitation: token-level distillation implicitly treats all output tokens as equally informative, but long-form outputs are dominated by high-frequency template and grammatical tokens, while the tokens that actually determine output quality are sparsely distributed. In medical report generation (MRG), two such decisive tokens stand out: pathology-related tokens that determine diagnostic content, and the end-of-sequence (EOS) event that determines termination. Both receive insufficient supervision under uniform cross-entropy, and autoregressive decoding further compounds the problem by drifting away from teacher-forced trajectories. We propose DIVE, a frozen-backbone distillation framework that addresses long-form report generation through two complementary mechanisms matched to these failures. Decisive-token supervision restores supervision balance by upweighting the cross-entropy contribution of pathology-related tokens and the EOS event, ensuring that content fidelity and termination are learned during training rather than imposed at decoding time. State-conditioned dynamic steering replaces fixed open-loop residuals with hidden-state-dependent adapters, allowing the injected signal to adapt as decoding drifts. Experiments on MIMIC-CXR and CheXpert Plus with two medical VLM backbones show that DIVE consistently ranks among the strongest methods across lexical and clinical-proxy metrics. Our method achieves the best BLEU-4, ROUGE-L, and RadGraph F1 in all dataset--backbone settings, while remaining competitive on coarse label-level CheXbert F1.

Digital pathology archives increasingly contain multiple whole-slide images (WSIs) per case, capturing spatially distinct tumor regions and reflecting intrinsic morphological heterogeneity. However, most existing approaches rely on a single pathologist-selected slide, thereby discarding potentially informative evidence distributed across the remaining WSIs. To date, no autonomous framework has been proposed for comprehensive multi-WSI case processing. Here, we present an unsupervised framework for case-level analysis that integrates information from all available slides within a case. Rather than relying on a single designated slide, the proposed approach constructs case-level representations by selectively distilling informative patches across WSIs. We introduce Clustering-Based Redundancy-Reduced Instance Sampling for Pathology (CRISP), a two-stage framework that first reduces redundancy within individual WSIs and subsequently applies clustering-based sampling to select a compact yet representative set of patches for the entire case. The resulting patch set captures case-level heterogeneity while avoiding exhaustive processing of gigapixel images, and directly serves as a retrieval index. Using two Mayo Clinic breast cancer datasets for diagnosis and treatment planning, we demonstrate that CRISP consistently matches or surpasses the current standard practice of combined model and pathologist slide selection for patient/case search and retrieval. By automating case-level processing and eliminating subjective WSI selection, CRISP potentially enables the exploitation of clinically relevant information distributed across multiple WSIs that is currently overlooked.

Recent advances in Multimodal Large Language Models (MLLMs) and agent workflows have shown strong promise for computational pathology, yet reliable patch-level reasoning remains challenging. End-to-end pathology MLLMs often hallucinate morphological features, while recent agentic systems usually merge tool outputs and retrieved knowledge into a shared context, making decisions vulnerable to conflicting evidence and context contamination. We propose PathoSage, a three-stage framework that explicitly separates knowledge retrieval, evidence collection, and evidence adjudication for patch-level pathology multimodal reasoning. Its core component, Structured Evidence Deliberation, independently evaluates heterogeneous evidence from tools, performs conflict analysis, and generates the final judgment in a fresh context to reduce anchoring bias. We further introduce a training-free Beta-Bernoulli experience system with continuous credit assignment to model long-term tool reliability and construct similarity-weighted priors for future tool use. Experiments show that PathoSage effectively mitigates VQA hallucinations and classifier disagreement, outperforming strong pathology MLLM and agentic baselines. Our results highlight explicit evidence adjudication and reliability-aware tool modeling as key ingredients for robust pathology agents.

Multiple instance learning (MIL) is the dominant framework for whole-slide image analysis in computational pathology, typically combining a frozen patch encoder, a projection layer, and a slide-level aggregator. While encoders and aggregators have been extensively studied, the projection layer remains a largely morphology-only bottleneck. This limits endpoints such as biomarker status and survival, which are governed by a molecular state that is not fully captured by H&E morphology. We introduce Molecularly Informed Staining Transform (MIST), a plug-in replacement for the MIL projection layer that uses paired spatial transcriptomics only during training to construct virtual molecular stains. MIST clusters gene expression profiles into cross-modal prototypes, anchors them in the frozen foundation model feature space, and uses them to reorganize H&E patch features along molecularly guided axes. It requires no transcriptomics at inference and can be inserted before standard MIL aggregators. We evaluate MIST across 23 downstream tasks and 8 MIL aggregators. MIST improves 240 of 256 configurations over the standard projection layer, with an average gain of +3.5%, observed consistently across endpoint types: +5.2% on survival prediction, +3.3% on tissue subtyping, and +2.6% on biomarker prediction. Ablations confirm that gene-derived prototypes are the primary source of the gains, while spatial, biological, and pathological analyses show that cross-modal prototype affinities capture spatially coherent molecular programs from H&E alone.

Concept Bottleneck Models (CBMs) in medical imaging aim to improve model interpretability by predicting intermediate clinical concepts before final diagnoses. However, most existing CBMs treat concepts as discriminative predictors of pathology labels, without explicitly modelling the underlying clinical generative process where diseases produce observable radiographic findings. We propose XpertCausal, a radiologist-guided causal CBM for chest X-ray interpretation which models pathology-to-concept relationships using a probabilistic noisy-OR framework. This generative model is then inverted via Bayesian inference to estimate pathology probabilities from predicted concepts. Radiologist-curated concept-pathology associations are used to constrain model structure to radiologist-defined clinically plausible reasoning pathways. We evaluate XpertCausal on MIMIC-CXR across pathology classification performance, calibration, explanation quality, and alignment with radiologist-defined reasoning pathways. Compared with both a non-causal CBM baseline and a causal ablation with unconstrained learned associations, XpertCausal achieves improved AUROC, calibration, and clinically relevant explanation quality, while learning concept-pathology relationships that more closely align with expert knowledge. These results demonstrate that incorporating clinically motivated causal structure and expert domain knowledge into CBMs can lead to more accurate, interpretable, and clinically aligned models for CXR interpretation.

Vision-language models (VLMs) have shown potential for automated radiology report generation, yet existing approaches rely on global embedding compression of volumetric data, often leading to hallucinated findings and limited anatomical grounding in 3D CT imaging. We introduce MedScribe, a hypothesis-driven framework that reformulates report generation as an iterative evidence acquisition process rather than a single-pass encoding task. MedScribe models reporting as a sequential decision process in which a large language model dynamically invokes pathology-specific diagnostic tools to extract localized volumetric features. These structured features are used to query a multidimensional retrieval space aligned with pathology-specific textual evidence. By explicitly accumulating quantitative evidence prior to synthesis, the framework enforces fine-grained grounding and reduces unsupported claims. Without task-specific fine-tuning, MedScribe improves clinical accuracy, factual consistency, and interpretability on CT-RATE and RadChestCT compared to state-of-the-art 2D and 3D VLMs, demonstrating the value of hypothesis-driven reasoning for reliable medical image reporting.

Vision foundation models (VFMs), such as DINOv3, provide rich semantic representations that are promising for computational pathology. However, many current adaptations pair frozen VFMs with lightweight decoders, creating a capacity mismatch that often limits boundary fidelity for infiltrative tumor bulk segmentation. This paper presents Dino-NestedUNet, a framework that couples a pre-trained DINOv3 encoder with a Nested Dense Decoder. Instead of sparse skip connections and linear upsampling, the proposed decoder forms a dense grid of intermediate pathways to enable continuous feature reuse and multi-scale recalibration, aligning high-level semantics with low-level morphological textures during reconstruction. We evaluate Dino-NestedUNet on three histopathology cohorts (multi-center CHTN, institutional OSU, and CAMELYON16) and observe consistent improvements over UNet++ and standard Dino-UNet variants, particularly under cross-domain shift. To further assess external generalization, we perform zero-shot evaluation by training on CHTN and directly testing on unseen TIGER WSIBULK and OSU CRC cohorts without fine-tuning. These results suggest that dense decoding is a key ingredient for unlocking foundation encoders in boundary-sensitive pathology segmentation.

Pathology reports are structured, multi-granular documents encoding diagnostic conclusions, histological grades, and ancillary test results across one or more anatomical sites; yet existing pathology vision-language models (VLMs) reduce this output to a flat label or free-form text. We present HiPath, a lightweight VLM framework built on frozen UNI2 and Qwen3 backbones that treats structured report prediction as its primary training objective. Three trainable modules totalling 15M parameters address complementary aspects of the problem: a Hierarchical Patch Aggregator (HiPA) for multi-image visual encoding, Hierarchical Contrastive Learning (HiCL) for cross-modal alignment via optimal transport, and Slot-based Masked Diagnosis Prediction (Slot-MDP) for structured diagnosis generation. Trained on 749K real-world Chinese pathology cases from three hospitals, HiPath achieves 68.9% strict and 74.7% clinically acceptable accuracy with a 97.3% safety rate, outperforming all baselines under the same frozen backbone. Cross-hospital evaluation confirms generalisation with only a 3.4pp drop in strict accuracy while maintaining 97.1% safety.

Molecular biomarker testing in pathology is often costly and tissue-consuming, limiting scalable clinical deployment. Artificial intelligence applied to hematoxylin and eosin (HE)-stained histology could enable rapid biomarker screening, but clinical translation requires models that are both accurate and interpretable. Here we introduce Hireca, a biomarker-focused pathology foundation model pretrained on more than 80,000 whole-slide images spanning 38 organ types from three medical centers, together with CytoMap, an interpretability module that localizes cellular-scale evidence underlying predictions. Across 10 biomarker tasks encompassing morphological, molecular, genetic, and spatial-transcriptomic-proxy readouts, Hireca ranked first in five tasks and outperformed comparable models overall. In evaluation by eight pathologists from two countries, CytoMap was consistently preferred over alternative visualization approaches and revealed error patterns in difficult cases. These results position Hireca and CytoMap as a transparent framework for clinically reviewable biomarker assessment directly from routine HE histology.

To overcome the black-box nature of predictive AI and the hallucination risks of generative models, retrieval-based models offer an interpretable, evidence-based paradigm for pathology clinical workflow. However, real-world clinical queries are inherently interleaved (e.g., pathology images and text). Current dual-encoders suffer from an \textbf{Architectural Mismatch}, lacking the mechanism to fuse such composed queries. To address this, we formalize the task of Pathology Composed Retrieval (PCR). While Multimodal Large Language Models (MLLMs) offer deep-fusion capabilities, directly applying them exposes a \textbf{Task Mismatch} and a \textbf{Domain Mismatch}. To resolve these challenges, we propose HOMIE, a model-agnostic adaptation framework that transforms any generative MLLM into a specialized pathology retrieval expert. Evaluated on our newly introduced PCR Benchmark, a lightweight 2B-parameter HOMIE variant substantially outperforms existing paradigms, surpassing specialized 7B pathology MLLMs and dual-encoders by large margins on composed retrieval, while maintaining strong performance on traditional simple retrieval. The project page is available at https://qfchou.github.io/HOMIE_page/.