TVT-PAPD: Pathology-Aware Prototype Distillation for Self-Supervised Whole Slide Image Classification

Ramesh Naidu Laveti, Jaya Sreevalsan-Nair, T K Srikanth

Self-supervised learning (SSL) has emerged as an effective paradigm for learning transferable representations from large-scale unlabeled whole slide images (WSIs). However, existing SSL methods primarily learn generic visual features and often fail to explicitly capture pathology-specific morphological patterns that are critical for disease characterization. To address this limitation, we propose Tiny Vision Transformer with Pathology-Aware Prototype Distillation (TVT-PAPD). This self-supervised pathology representation learning framework integrates a Tiny Vision Transformer (TVT) with a novel Pathology-Aware Prototype Distillation (PAPD) module. PAPD employs a learnable pathology prototype bank to discover and preserve representative tissue morphology patterns, encouraging semantically similar pathological regions to learn consistent and discriminative representations. The proposed framework enhances pathology-aware feature learning while maintaining computational efficiency with 90M parameters. Experiments on the Cancer Genome Atlas (TCGA) low-grade glioma (LGG)/glioblastoma (GBM) dataset and the Indian Pathology Brain (IPD-Brain) dataset demonstrate that TVT-PAPD achieves weighted F1-scores of 93.02% and 90.23%, respectively, for LGG-GBM classification, while exhibiting strong cross-cohort generalization across independent glioma datasets.