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.

The authors have declared no competing interest.

This study did not receive any funding

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study used ONLY openly available human data that were initially located at https://www.cancer.gov/ccg/research/genome-sequencing/tcga

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes