LiteMIL: A Computationally Efficient Transformer-Based MIL for Cancer Subtyping on Whole Slide Images

ABSTRACT Purpose Accurate cancer subtyping is crucial for effective treatment; however, it presents challenges due to overlapping morphology and variability among pathologists. Although deep learning (DL) methods have shown potential, their application to gigapixel whole slide images (WSIs) is often hindered by high computational demands and the need for efficient, context-aware feature aggregation. This study introduces LiteMIL, a computationally efficient transformer-based multiple instance learning (MIL) network combined with Phikon, a pathology-tuned self-supervised feature extractor, for robust and scalable cancer subtyping on WSIs. Methods Initially, patches were extracted from TCGA-THYM dataset (242 WSIs, six subtypes) and subsequently fed in real-time to Phikon for feature extraction. To train MILs, features were arranged into uniform bags using a chunking strategy that maintains tissue context while increasing training data. LiteMIL utilizes a learnable query vector within an optimized multi-head attention module for effective feature aggregation. The model’s performance was evaluated against established MIL methods on the Thymic Dataset and three additional TCGA datasets (breast, lung, and kidney cancer). Results LiteMIL achieved 0.89 ± 0.01 F1 score and 0.99 AUC on Thymic dataset, outperforming other MILs. LiteMIL demonstrated strong generalizability across the external datasets, scoring the best on breast and kidney cancer datasets. Compared to TransMIL, LiteMIL significantly reduces training time and GPU memory usage. Ablation studies confirmed the critical role of the learnable query and layer normalization in enhancing performance and stability. Conclusion LiteMIL offers a resource-efficient, robust solution. Its streamlined architecture, combined with the compact Phikon features, makes it suitable for integrating into routine histopathological workflows, particularly in resource-limited settings.