Pathology foundation models (PFMs) are increasingly used as general-purpose backbones, yet existing benchmarks cannot systematically diagnose their whole-slide cellular representation capabilities, including the decodability of cell-type information and the transferability of such information across tissue sections, datasets, and anatomical organs. We introduce CellPath-Bench, a cellular-resolution benchmark that evaluates frozen PFMs themselves. Following quality control of 52 candidate Xenium datasets, we construct a panel of 25 spatially aligned H\&E--Xenium tissue sections spanning 11 organs and 7,079,283 cells, harmonized into fine- and coarse-grained taxonomies. CellPath-Bench samples frozen WSI feature maps at registered nuclear coordinates and evaluates them using standardized multiclass linear probes. Cell Representation Advantage (CRA) measures the within-section advantage of nucleus-anchored representations over patch-level mean pooling, while Cell Representation Transferability (CRT) characterizes the generalization of cell-type decodability across tissue sections, datasets, and organs. We benchmark 30 pathology-specific and general-purpose foundation models through 304,920 runs across spatial readouts, magnifications, taxonomic granularities, and evaluation protocols. The results reveal substantial model-dependent differences in cell-type decodability and its cross-domain generalization, yielding distinct multidimensional capability profiles. CellPath-Bench provides a standardized framework for auditing cellular information in frozen PFM representations.
Whole-slide pathology reasoning requires models to integrate gigapixel-scale visual evidence across complete case-linked slides, yet current question-answering benchmarks primarily measure final answer accuracy--a metric vulnerable to linguistic priors and benchmark regularities, and insufficient to establish that predictions are grounded in the supplied tissue. We introduce PathoArgus-Bench, a benchmark and evaluation protocol that explicitly tests the full evidence chain: availability, accessibility, use, and responsiveness. PathoArgus-Bench comprises 22,078 four-choice questions from 4,913 patients across 15 TCGA projects, covering six pathology capabilities across three levels of evidence demand, and operates under a fixed reader budget that retains only a small fraction of the gigapixel context. To further isolate evidence-grounded reasoning, we contribute ESG (Evidence State Quartets), a controlled set of 483 quartets where the question text is fixed while the target WSI set is moved, replaced, or removed, requiring consistent predictions across all states. Evaluating 20 general-purpose, medical, and pathology-specific systems reveals a stark gap: while GPT-5.6 achieves 57.09% overall accuracy and 57.04% on ESG, it correctly completes only 19 of 483 quartets (3.93% QExact), exposing that row-level accuracy does not translate into reliable evidence grounding. We also introduce PathoArgus, a fixed-budget reader that allocates context via question relevance and spatial coverage, attaining 50.39% overall accuracy yet only 1.86% QExact--demonstrating that improved context access alone does not ensure consistent evidence-based prediction. Our benchmark and diagnostics establish that acquiring useful whole-slide context is necessary but far from sufficient, and call for a shift from answer-centric to evidence-grounded evaluation in computational pathology.
Whole-slide multiple-instance learning (MIL) observes only the patches admitted by its selector. Deployment can alter this selector through compute limits, tissue masking, or regional workflows, even when the patch count is unchanged. We introduce BagShift, a paired protocol that changes the selector for the same case while holding its features and predictor fixed, thereby isolating selector response from case mix. With equal 128-patch budgets, sampling across the tissue or concentrating around one coordinate exposes markedly different evidence: on PANDA, the two views reduce quadratic weighted kappa by 1.57 and 17.96 points, respectively (QWK reported on the $\times100$ scale). On CAMELYON16, lesion annotations withheld from model development show that localized views retain tumor in only 10.0\% of micrometastatic observations, and matched exposure does not consistently recover the loss. The same fixed-count stressor produces a much smaller response on external lung subtyping, although differences in relative coverage make cross-task severity descriptive. When repeated localized observations are available, unioning their patches before one nonlinear MIL pass improves PANDA QWK by 7.87 points over averaging regional predictions. Patch count specifies computation, not observed evidence; deployment evaluations should report both what a selector preserves and how repeated observations are aggregated.
Foundation models are reshaping computational pathology, yet their capabilities remain shaped by pretraining objectives, data sources, and spatial scales, fragmenting complementary expertise across separate backbones. Here we present ALICE, a unified foundation model trained through multi-stage agglomerative distillation that sequentially distills eight vision-only, vision-language, and slide-level teacher models into dedicated modules of a single backbone. ALICE is pretrained on 24,985,184 tile-level pathology images and 155,604 high-resolution images, and evaluated across 21 task scenarios, 96 downstream tasks, and 48 data sources, spanning region-of-interest tissue analysis, vision-language multimodal evaluation, and whole-slide clinical assessment. In all three evaluation settings, ALICE achieved the best average rank among task-matched pathology foundation models. These results demonstrate that agglomerative distillation can consolidate complementary capabilities from specialized models into a unified backbone for broad computational pathology applications. The model is available at https://github.com/WonderLandxD/ALICE.
As hematoxylin & eosin (H&E) staining constitutes the primary entry point in routine diagnostic workflows, computer-aided diagnosis from whole-slide H&E images is of particular clinical relevance. However, substantial variability in specimen preparation, staining protocols, and scanning conditions, together with inherent uncertainty in expert pixel-level annotations, makes automated analysis of H&E-stained images challenging. In this study, we propose a semantic segmentation-based framework for image-level diagnosis, grounded in the clinically motivated assumption that each histopathological image corresponds to a single cancer type. Image-level predictions are obtained by assigning the class of the dominant pixel-level label in the segmentation output. To ensure clinical relevance, we adopt the nnU-Net architecture and train it on a publicly available dataset collected in our study with pixel-level annotations for three liver cancer types: hepatocellular cacrcinoma (HCC; 55 images from 30 patients), cholangiocellular carcinoma (CCA; 55 images from 29 patients), and colorectal metastatic adenocarcinoma (CMA; 60 images from 30 patients). Annotations were independently provided by four pathologist. We hypothesize that the combination of stain normalization and semantic segmentation mitigates domain shift and reduces sensitivity to annotation noise. Five-fold cross-validation yielded balanced accuracy of 0.975 (HCC), 0.950 (CCA), and 1.000 (CMA), comparable to results obtained with immunohosthochemical staining and superior to several deep learning models trained on patch-level annotations. The proposed framework has the potential to support pathologists in prioritizing immunohistochemical marker selection, thereby reducing diagnostic costs and turnaround time. Integration with immunohistochemical findings improve overall diagnostic reliability.
Spatial transcriptomics (ST) links gene expression with tissue morphology but remains expensive and low-throughput, motivating surrogates that infer expression from routine histology. Whole-slide H&E-to-ST inference pairs a gigapixel image with gene measurements at a sparse, irregular set of locations, making multiscale modeling challenging without incurring dense-grid overhead or quadratic token mixing. We propose HiST, a hierarchical sparse transformer that treats measured locations as a lattice-indexed sparse field and builds a dyadic encoder--decoder directly on the active tissue footprint. HiST combines sparse window attention for local geometric correspondence with resolution-changing operators for rapid multiscale context integration. For a fixed window size, the dominant runtime and memory scale with the number of observed locations rather than the dense slide area. To mitigate slide-specific acquisition variation, HiST adds a bottlenecked global conditioning pathway via a \emph{slide calibration token} that summarizes slide-level context and conditions local representations. On a multi-organ benchmark spanning diverse tissues and acquisition sources, HiST improves predictive performance over recent baselines while reducing runtime and peak memory.
Bokai Zhao, Yiyang Zhang, Long Bai +3eess.IV cs.AI cs.CV
Computational pathology requires visual representations that transfer across diverse clinical endpoints and remain robust to variation in magnification, staining, scanner type, slide preparation, and input resolution. We present DaX, a pathology vision foundation model that adapts DINOv3-style self-supervised learning to whole-slide histopathology. DaX is initialized from natural-image DINOv3 weights and incorporates continuous magnification training, cross-scale tissue views, orientation-agnostic and acquisition-robust augmentation, multi-input-size training, and Gram-anchored dense consistency. These designs aim to connect local cellular morphology with global tissue architecture while stabilizing dense token-level representations across input scales. We further construct a WSI-level benchmark comprising 161 clinically meaningful tasks from 44 public datasets, covering 28,182 patients and 34,394 slides across four clinical domains and nine task categories. All models are evaluated under a fixed patient-level cross-validation protocol with fold-level statistical ranking, enabling reproducible comparisons that are less sensitive to split-dependent variation. Across this benchmark, DaX achieves the highest mean performance across tasks and consistently strong task-level ranking scores, with gains spanning diagnostic pathology, biomarker and molecular profiling, tissue/specimen context, and risk, response, and prognosis. These results support DaX as a transferable visual encoder for computational pathology and provide a standardized evaluation framework for future pathology foundation models. Project page: https://alibaba-damo-academy.github.io/DaX/benchboard/.