Exploiting Spatial Structure for Transductive Few-Shot Classification of Whole-Slide Images

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.

Whole Slide Images (WSIs) are giga-pixel in scale and are typically partitioned into small instances in WSI classification pipelines for computational feasibility. However, obtaining extensive instance level annotations is costly, making few-shot weakly supervised WSI classification (FSWC) crucial for learning from limited slide-level labels. Recently, pre-trained vision-language models (VLMs) have been adopted in FSWC, yet they exhibit several limitations. Existing prompt tuning methods in FSWC substantially increase both the number of trainable parameters and inference overhead. Moreover, current methods discard instances with low alignment to text embeddings from VLMs, potentially leading to information loss. To address these challenges, we propose two key contributions. First, we introduce a new parameter efficient prompt tuning method by scaling and shifting features in text encoder, which significantly reduces the computational cost. Second, to leverage not only the pre-trained knowledge of VLMs, but also the inherent hierarchical structure of WSIs, we introduce a WSI representation learning approach with a soft hierarchical textual guidance strategy without utilizing hard instance filtering. Comprehensive evaluations on pathology datasets covering breast, lung, and ovarian cancer types demonstrate consistent improvements up-to 10.9%, 7.8%, and 13.8% respectively, over the state-of-the-art methods in FSWC. Our method reduces the number of trainable parameters by 18.1% on both breast and lung cancer datasets, and 5.8% on the ovarian cancer dataset, while also excelling at weakly-supervised tumor localization. Code at https://github.com/Jayanie/HIPSS.

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