Wataru Uegami

Zahra Rahimi Afzal, Wataru Uegami, Saghir Alfasly et al.

Digital pathology archives increasingly contain multiple whole-slide images (WSIs) per case, capturing spatially distinct tumour regions and reflecting intrinsic morphological heterogeneity. However, most existing approaches rely on a single pathologist-selected slide, thereby discarding potentially informative evidence distributed across the remaining WSIs. To date, no autonomous framework has been proposed for comprehensive multi-WSI case processing. Here, we present an unsupervised framework for case-level analysis that integrates information from all available slides within a case. Rather than relying on a single designated slide, the proposed approach constructs case-level representations by selectively distilling informative patches across WSIs. We introduce Clustering-Based Redundancy-Reduced Instance Sampling for Pathology (CRISP), a two-stage framework that first reduces redundancy within individual WSIs and subsequently applies clustering-based sampling to select a compact yet representative set of patches for the entire case. The resulting patch set captures case-level heterogeneity while avoiding exhaustive processing of gigapixel images, and directly serves as a retrieval index. Using two Mayo Clinic breast cancer datasets for diagnosis and treatment planning, we demonstrate that CRISP consistently matches or surpasses the current standard practice of combined model and pathologist slide selection for patient/case search and retrieval. By automating case-level processing and eliminating subjective WSI selection, CRISP potentially enables the exploitation of clinically relevant information distributed across multiple WSIs that is currently overlooked.

Md. Enamul Hoq, Wataru Uegami, Saghir Alfasly et al.

Generative vision-language models can produce fluent medical image captions but remain prone to hallucination, over-specific diagnostic claims, and factual inconsistency-serious issues in pathology. We investigate retrieval-guided generation (RGG) as a safer alternative, where captions are formed by summarizing expert text from visually similar cases rather than generated de novo. On the ARCH histopathology dataset, RGG improves semantic alignment with ground truth, achieving cosine similarity of $\approx$0.60 versus $\approx$0.47 from MedGemma, with non-overlapping confidence intervals indicating a robust gain. A pathologist-led qualitative review shows better preservation of morphology-relevant terminology and fewer unsupported diagnoses, while revealing failure modes such as concept mixing and inherited over-specific labeling. Overall, retrieval-guided captioning offers a more transparent and reliable approach with clearer opportunities for auditing than fully generative methods.

Tianhao Lei, Parsa Esmaeilkhani, Saghir Alfasly et al.

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.

Jialiang Geng, Ghazal Alabtah, Saghir Alfasly et al.

The rapid growth of digital pathology has created an urgent need for efficient indexing and retrieval of whole slide images (WSIs). This need is intensified by emerging generative AI workflows, particularly retrieval-augmented generation (RAG), which require dependable similarity search to support high-stakes clinical decision-making. Yet the substantial cost of high-performance storage limits the scalability and accessibility of WSI indexing for many healthcare institutions. Consequently, methods that can reduce storage demands while preserving retrieval accuracy have become a critical research priority. We propose ARReST (Antithetical Redundancy Reduction Strategy), a principled oppositional framework that leverages redundancy across dissimilar tissue classes to markedly decrease the number of patches that must be indexed from each WSI. Instead of eliminating only within-class duplicates, ARReST identifies antithetical patches-those whose representations contribute minimally to cross-class discrimination-and prunes them from the searchable archive. This targeted reduction substantially compresses the index without sacrificing morphological diversity or retrieval fidelity. By minimizing superfluous patch representations, ARReST reduces storage footprint, lowers computational overhead, and accelerates similarity search across large pathology repositories. Extensive experiments on TCGA repository (The Cancer Genome Atlas with 21 organs) demonstrate that ARReST achieves significant index compression while maintaining competitive retrieval performance. The observed storage savings of 3% to 60% (14%$\pm$13%) can be reliably achieved without compromising retrieval performance for many organs. The proposed strategy enables scalable, cost-efficient WSI indexing and is well-suited for next-generation retrieval-driven clinical AI systems.

Saghir Alfasly, Wataru Uegami, MD Enamul Hoq et al.

Synthetic data generation in histopathology faces unique challenges: preserving tissue heterogeneity, capturing subtle morphological features, and scaling to unannotated datasets. We present a latent diffusion model that generates realistic heterogeneous histopathology images through a novel dual-conditioning approach combining semantic segmentation maps with tissue-specific visual crops. Unlike existing methods that rely on text prompts or abstract visual embeddings, our approach preserves critical morphological details by directly incorporating raw tissue crops from corresponding semantic regions. For annotated datasets (i.e., Camelyon16, Panda), we extract patches ensuring 20-80% tissue heterogeneity. For unannotated data (i.e., TCGA), we introduce a self-supervised extension that clusters whole-slide images into 100 tissue types using foundation model embeddings, automatically generating pseudo-semantic maps for training. Our method synthesizes high-fidelity images with precise region-wise annotations, achieving superior performance on downstream segmentation tasks. When evaluated on annotated datasets, models trained on our synthetic data show competitive performance to those trained on real data, demonstrating the utility of controlled heterogeneous tissue generation. In quantitative evaluation, prompt-guided synthesis reduces Frechet Distance by up to 6X on Camelyon16 (from 430.1 to 72.0) and yields 2-3x lower FD across Panda and TCGA. Downstream DeepLabv3+ models trained solely on synthetic data attain test IoU of 0.71 and 0.95 on Camelyon16 and Panda, within 1-2% of real-data baselines (0.72 and 0.96). By scaling to 11,765 TCGA whole-slide images without manual annotations, our framework offers a practical solution for an urgent need for generating diverse, annotated histopathology data, addressing a critical bottleneck in computational pathology.