Tissue Classification and Whole-Slide Images Analysis via Modeling of the Tumor Microenvironment and Biological Pathways

Automatic integration of whole slide images (WSIs) and gene expression profiles has demonstrated substantial potential in precision clinical diagnosis and cancer progression studies. However, most existing studies focus on individual gene sequences and slide level classification tasks, with limited attention to spatial transcriptomics and patch level applications. To address this limitation, we propose a multimodal network, BioMorphNet, which automatically integrates tissue morphological features and spatial gene expression to support tissue classification and differential gene analysis. For considering morphological features, BioMorphNet constructs a graph to model the relationships between target patches and their neighbors, and adjusts the response strength based on morphological and molecular level similarity, to better characterize the tumor microenvironment. In terms of multimodal interactions, BioMorphNet derives clinical pathway features from spatial transcriptomic data based on a predefined pathway database, serving as a bridge between tissue morphology and gene expression. In addition, a novel learnable pathway module is designed to automatically simulate the biological pathway formation process, providing a complementary representation to existing clinical pathways. Compared with the latest morphology gene multimodal methods, BioMorphNet's average classification metrics improve by 2.67%, 5.48%, and 6.29% for prostate cancer, colorectal cancer, and breast cancer datasets, respectively. BioMorphNet not only classifies tissue categories within WSIs accurately to support tumor localization, but also analyzes differential gene expression between tissue categories based on prediction confidence, contributing to the discovery of potential tumor biomarkers.

A Multicenter Benchmark of Multiple Instance Learning Models for Lymphoma Subtyping from HE-stained Whole Slide Images

Timely and accurate lymphoma diagnosis is essential for guiding cancer treatment. Standard diagnostic practice combines hematoxylin and eosin (HE)-stained whole slide images with immunohistochemistry, flow cytometry, and molecular genetic tests to determine lymphoma subtypes, a process requiring costly equipment, skilled personnel, and causing treatment delays. Deep learning methods could assist pathologists by extracting diagnostic information from routinely available HE-stained slides, yet comprehensive benchmarks for lymphoma subtyping on multicenter data are lacking. In this work, we present the first multicenter lymphoma benchmarking dataset covering four common lymphoma subtypes and healthy control tissue. We systematically evaluate five publicly available pathology foundation models (H-optimus-1, H0-mini, Virchow2, UNI2, Titan) combined with attention-based (AB-MIL) and transformer-based (TransMIL) multiple instance learning aggregators across three magnifications (10x, 20x, 40x). On in-distribution test sets, models achieve multiclass balanced accuracies exceeding 80% across all magnifications, with all foundation models performing similarly and both aggregation methods showing comparable results. The magnification study reveals that 40x resolution is sufficient, with no performance gains from higher resolutions or cross-magnification aggregation. However, on out-of-distribution test sets, performance drops substantially to around 60%, highlighting significant generalization challenges. To advance the field, larger multicenter studies covering additional rare lymphoma subtypes are needed. We provide an automated benchmarking pipeline to facilitate such future research.

Domain-incremental White Blood Cell Classification with Privacy-aware Continual Learning

White blood cell (WBC) classification plays a vital role in hematology for diagnosing various medical conditions. However, it faces significant challenges due to domain shifts caused by variations in sample sources (e.g., blood or bone marrow) and differing imaging conditions across hospitals. Traditional deep learning models often suffer from catastrophic forgetting in such dynamic environments, while foundation models, though generally robust, experience performance degradation when the distribution of inference data differs from that of the training data. To address these challenges, we propose a generative replay-based Continual Learning (CL) strategy designed to prevent forgetting in foundation models for WBC classification. Our method employs lightweight generators to mimic past data with a synthetic latent representation to enable privacy-preserving replay. To showcase the effectiveness, we carry out extensive experiments with a total of four datasets with different task ordering and four backbone models including ResNet50, RetCCL, CTransPath, and UNI. Experimental results demonstrate that conventional fine-tuning methods degrade performance on previously learned tasks and struggle with domain shifts. In contrast, our continual learning strategy effectively mitigates catastrophic forgetting, preserving model performance across varying domains. This work presents a practical solution for maintaining reliable WBC classification in real-world clinical settings, where data distributions frequently evolve.

B-Cos Aligned Transformers Learn Human-Interpretable Features

Vision Transformers (ViTs) and Swin Transformers (Swin) are currently state-of-the-art in computational pathology. However, domain experts are still reluctant to use these models due to their lack of interpretability. This is not surprising, as critical decisions need to be transparent and understandable. The most common approach to understanding transformers is to visualize their attention. However, attention maps of ViTs are often fragmented, leading to unsatisfactory explanations. Here, we introduce a novel architecture called the B-cos Vision Transformer (BvT) that is designed to be more interpretable. It replaces all linear transformations with the B-cos transform to promote weight-input alignment. In a blinded study, medical experts clearly ranked BvTs above ViTs, suggesting that our network is better at capturing biomedically relevant structures. This is also true for the B-cos Swin Transformer (Bwin). Compared to the Swin Transformer, it even improves the F1-score by up to 4.7% on two public datasets.

Data Models for Dataset Drift Controls in Machine Learning With Images

Camera images are ubiquitous in machine learning research. They also play a central role in the delivery of important services spanning medicine and environmental surveying. However, the application of machine learning models in these domains has been limited because of robustness concerns. A primary failure mode are performance drops due to differences between the training and deployment data. While there are methods to prospectively validate the robustness of machine learning models to such dataset drifts, existing approaches do not account for explicit models of the primary object of interest: the data. This makes it difficult to create physically faithful drift test cases or to provide specifications of data models that should be avoided when deploying a machine learning model. In this study, we demonstrate how these shortcomings can be overcome by pairing machine learning robustness validation with physical optics. We examine the role raw sensor data and differentiable data models can play in controlling performance risks related to image dataset drift. The findings are distilled into three applications. First, drift synthesis enables the controlled generation of physically faithful drift test cases. The experiments presented here show that the average decrease in model performance is ten to four times less severe than under post-hoc augmentation testing. Second, the gradient connection between task and data models allows for drift forensics that can be used to specify performance-sensitive data models which should be avoided during deployment of a machine learning model. Third, drift adjustment opens up the possibility for processing adjustments in the face of drift. This can lead to speed up and stabilization of classifier training at a margin of up to 20% in validation accuracy. A guide to access the open code and datasets is available at https://github.com/aiaudit-org/raw2logit.