The effective management of brain tumors relies on precise typing, subtyping, and grading. This study advances patient care with findings from rigorous multiple instance learning experimentations across various feature extractors and aggregators in brain tumor histopathology. It establishes new performance benchmarks in glioma subtype classification across multiple datasets, including a novel dataset focused on the Indian demographic (IPD- Brain), providing a valuable resource for existing research. Using a ResNet-50, pretrained on histopathology datasets for feature extraction, combined with the Double-Tier Feature Distillation (DTFD) feature aggregator, our approach achieves state-of-the-art AUCs of 88.08 on IPD-Brain and 95.81 on the TCGA-Brain dataset, respectively, for three-way glioma subtype classification. Moreover, it establishes new benchmarks in grading and detecting IHC molecular biomarkers (IDH1R132H, TP53, ATRX, Ki-67) through H&E stained whole slide images for the IPD-Brain dataset. The work also highlights a significant correlation between the model decision-making processes and the diagnostic reasoning of pathologists, underscoring its capability to mimic professional diagnostic procedures.
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