# Hierarchical Prototype-based Domain Priors for Multiple Instance Learning in Multimodal Histopathology Analysis

arXiv: https://arxiv.org/abs/2604.23982 · HTML: https://mlsanity.com/paper/2604.23982/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 11 of its 31 references that are in the map.
- First posted on arXiv 27 Apr 2026.

## Builds on (most cited first, 11 of 11)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [BioBERT: a pre-trained biomedical language representation model for biomedical text mining](https://mlsanity.com/paper/1901.08746/) (2019)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [Quilt-1M: One Million Image-Text Pairs for Histopathology](https://mlsanity.com/paper/2306.11207/) (2023)
- [Whole Slide Images are 2D Point Clouds: Context-Aware Survival Prediction using Patch-based Graph Convolutional Networks](https://mlsanity.com/paper/2107.13048/) (2021)
- [Text-guided Foundation Model Adaptation for Pathological Image Classification](https://mlsanity.com/paper/2307.14901/) (2023)
- [Hierarchical Text-to-Vision Self Supervised Alignment for Improved Histopathology Representation Learning](https://mlsanity.com/paper/2403.14616/) (2024)
- [Prototype-Guided Cross-Modal Knowledge Enhancement for Adaptive Survival Prediction](https://mlsanity.com/paper/2503.10726/) (2025)

## Abstract (arXiv)

Digital pathology has fundamentally altered diagnostic workflows by enabling the computational analysis of gigapixel Whole Slide Images (WSIs), yet effectively deciphering their complex tumor microenvironments remains a formidable challenge. Existing Multiple Instance Learning (MIL) frameworks typically treat Whole Slide Images as unstructured bags of patches, discarding critical morphological semantics and spatial geometry. This lack of inductive bias often leads to overfitting on background noise and fails to align visual features with high-level diagnostic knowledge. To overcome these limitations, we propose the Hierarchical Prototype-based Domain Priors (HPDP) framework, a unified multimodal approach for joint histopathology diagnosis and prognosis. HPDP mitigates the data-driven "black box" issue by introducing a Morphologically Anchored Prototype System (MAPS), which anchors learning to interpretable morphological clusters, and a Sinusoidal Positional Encoder (SPE) to explicitly model tissue architecture. Furthermore, we bridge the semantic gap via a Hierarchical Cross-Modal Alignment (HCMA) module, using Large Language Model (LLM)-generated descriptions to contextually refine visual representations. Extensive experiments across seven cancer cohorts demonstrate that HPDP consistently achieves state-of-the-art performance with superior robustness and interpretability.