Automating the analysis of whole-slide images has high clinical value, since characterizing cancers requires examining them in detail. Such analysis increasingly relies on vision-language models that provide patch-level zero-shot predictions. However, these predictions remain noisy and must be refined with a few annotations. A promising paradigm for this refinement is few-shot transduction. Rather than treating each patch independently, these methods leverage the relations between patches, together with a few annotations, to refine all predictions jointly. However, current transductive methods are evaluated under conditions that overlook key properties of whole-slide images: (i) datasets consist of independent patches extracted from multiple slides, ignoring the complex tissue organization; (ii) datasets are mostly balanced, whereas a single whole-slide image exhibits severe class imbalance, with several classes absent; and (iii) annotations are sampled at random, without reflecting how a pathologist annotates a limited number of regions. To align the transduction paradigm to realistic whole-slide settings, we introduce the following contributions. First, we propose SlideCRF, which adapts conditional random fields for whole-slide images by combining spatial and biological cues while accounting for classes that may be absent from a given slide. Second, we provide a set of realistic annotation protocols, based on spatially localized clicks and scribbles, modeling different pathologist interactions, such as the iterative correction of model errors. Across four datasets, we show that SlideCRF outperforms current transductive methods in macro F1, improving over the zero-shot predictions by +24.2% and +37.5% with one and 16 clicks per present class, respectively.
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
Patient exams in the cancer diagnosis and staging process typically generate several whole slide images (WSIs). One of the initial steps in training models on WSI data is identifying one or a few slides containing tumor or other diagnostic biomarkers necessary for downstream prediction tasks such as estimating recurrence risk or progression-free survival. This step requires tedious manual curation by experienced pathologists. Many published datasets make the artificial assumption of 1 slide per patient. Alternatively, all slides per patient may be used for model training, which may dilute the signal from the few slides containing tumor or other relevant information. In this paper, we present a pipeline to overcome these challenges using publicly available WSI foundation models (FMs). Our evaluations show that ranking WSIs based on predictions from zero-shot classification using WSI FMs accurately identifies slides with the most tumor, indicating that WSI FMs contain sufficient morphology signal to automatically triage slides. We also present a formulation for ranked evaluation to benchmark FM performance in slide triage. We show, on multiple datasets, that tumor slides are identified in the top-2 ranked slides for patients with up to 43 slides.
Foreground segmentation is the critical first step of every computational pathology pipeline, yet existing methods rely on hand-tuned heuristics or supervised models that overfit to narrow stain and scanner distributions, failing silently on specialised stains such as Jones silver or Elastica van Gieson. We propose a coarse-to-fine approach that recasts foreground segmentation as a visual perception task and leverages general-purpose vision-language models (VLMs) as zero-annotation oracles. Our key insight is that tissue-versus-background discrimination is a natural-image recognition problem, not a histopathological one, so VLMs trained on internet-scale corpora generalise where domain-specific models cannot. We introduce Leica-75, a benchmark of 75 renal transplant whole-slide images spanning three stain families. On Leica-75, our method achieves the highest segmentation quality on out-of-distribution stains (Dice 0.858 +/- 0.027 on Jones, 0.853 +/- 0.041 on EVG) with 7x lower cross-stain variance than the best supervised baseline, while remaining competitive on in-distribution H&E. Few-shot prompting with automatically curated exemplars (Auto-context) rescues hard cases on Stress-32 (n=32), a curated stress-test subset (Dice 0.470 to 0.819 for the 2B model). VLM-based annotation review matches human expert consensus (kappa=0.989 for blur detection; mean precision/recall grading accuracy 0.708 vs. human 0.646 for segmentation mask review). The resulting pseudo-labels are used to distil lightweight student models that are as performant as the teacher model while running for a fraction of the cost. Our framework provides a principled, scalable solution to a persistent infrastructure bottleneck in digital pathology.