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.

Deep Learning Under the Microscope: Improving the Interpretability of Medical Imaging Neural Networks

In this paper, we propose a novel interpretation method tailored to histological Whole Slide Image (WSI) processing. A Deep Neural Network (DNN), inspired by Bag-of-Features models is equipped with a Multiple Instance Learning (MIL) branch and trained with weak supervision for WSI classification. MIL avoids label ambiguity and enhances our model's expressive power without guiding its attention. We utilize a fine-grained logit heatmap of the models activations to interpret its decision-making process. The proposed method is quantitatively and qualitatively evaluated on two challenging histology datasets, outperforming a variety of baselines. In addition, two expert pathologists were consulted regarding the interpretability provided by our method and acknowledged its potential for integration into several clinical applications.