With foundation-model features, aggregator complexity does not improve cross-hospital discrimination in gastric whole-slide image classification

Foundation models are reshaping computational histopathology, yet their value for whole-slide image retrieval relative to strong patch-based and supervised aggregation baselines remains unclear. We benchmarked ten pipelines on 9,387 diagnostic slides spanning 17 organs and 60 diagnoses from The Cancer Genome Atlas (TCGA) using patient-level leave-one-patient-out evaluation. Methods included four pre-trained slide foundation models, a supervised attention-based multiple instance learning (ABMIL) aggregator on patch embeddings, and patch-level retrieval across five sampling densities. Performance varied more across organs and diagnoses than across architectures. Although the slide foundation model TITAN achieved the strongest overall results, its advantage was modest; ABMIL and patch-based methods reached comparable Top-1 and Top-3 accuracy, with no model consistently dominant. Morphologically distinctive entities approached ceiling performance, while rare, heterogeneous, and closely related subtypes remained challenging. Misclassifications aligned with organs exhibiting known inter-observer variability, suggesting an intrinsic ceiling for morphology-only retrieval. Performance was driven primarily by patch-level feature representations, with limited benefit from slide-level aggregation, indicating aggregation may be unnecessary in many settings. These findings argue against a universally optimal architecture and instead support organ-resolved benchmarking, diagnosis-aware or ensemble strategies, stronger feature representations, and multimodal retrieval frameworks. Notably, even the best model achieved only $\approx 68\% \pm 21\%$ retrieval accuracy on TCGA, and some subtypes showed $0\%$ accuracy across all methods, highlighting fundamental limitations of morphology-based representations and the need for substantial progress before reliable clinical deployment.

Gastric adenocarcinoma (GA) is a leading cause of cancer-related mortality worldwide, and accurate histopathological subtype classification from whole-slide images (WSIs) is essential for effective treatment planning. While multimodal approaches that integrate pathology report text with WSIs can improve classification, existing methods often depend on computationally expensive transformer architectures and large language models. We propose a multimodal knowledge distillation (MKD) framework that combines a pretrained WSI image encoder and a clinical text encoder using Low-Rank Multimodal Fusion (LMF) to efficiently model cross-modal interactions during training. Each WSI is represented as a bag of patches paired with a slide-level diagnostic caption. The teacher model learns fused image-text representations for subtype classification, while the student model distills this knowledge to enable accurate image-only inference. We evaluate our method on the PatchGastric benchmark dataset and achieve at least 3.35% higher mean accuracy than state-of-the-art approaches, without relying on transformer-based fusion, multi-task learning, or large language models. The source code is available at https://github.com/helomelo1/MKD-LMF.

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.