Unified Multi-Foundation-Model Slide Representation for Pan-Cancer Recognition and Text-Guided Tumor Localization

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.

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.

Computational pathology needs whole-slide image (WSI) foundation models that transfer across diverse clinical tasks, yet current approaches remain largely slide-centric, often depend on private data and expensive paired-report supervision, and do not explicitly model relationships among multiple slides from the same patient. We present MOOZY, a patient-first pathology foundation model in which the patient case, not the individual slide, is the core unit of representation. MOOZY explicitly models dependencies across all slides from the same patient via a case transformer during pretraining, combining multi-stage self-supervision with scaled low-cost task supervision. In Stage 1, we pretrain a vision-only slide encoder on 77,134 public slide feature grids using masked self-distillation. In Stage 2, we align these representations with clinical semantics using a case transformer and multi-task supervision over 333 tasks from 56 public datasets, including 205 classification and 128 survival tasks across four endpoints. Across sixteen held-out tasks, MOOZY improves macro weighted F1, balanced accuracy, and macro weighted ROC-AUC relative to PRISM by +4.19%, +7.93%, and +6.95%, respectively. MOOZY is also parameter efficient with 85.77M parameters, 14$\times$ smaller than GigaPath. These results suggest that patient-level pretraining yields transferable embeddings, providing a path toward scalable patient-first histopathology foundation models.