# MacNet: An End-to-End Manifold-Constrained Adaptive Clustering Network for Interpretable Whole Slide Image Classification

arXiv: https://arxiv.org/abs/2602.14509 · HTML: https://mlsanity.com/paper/2602.14509/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 18 of its 30 references that are in the map.
- First posted on arXiv 16 Feb 2026.

## Builds on (most cited first, 18 of 18)

- [Swin Transformer: Hierarchical Vision Transformer using Shifted Windows](https://mlsanity.com/paper/2103.14030/) (2021)
- [ImageNet Large Scale Visual Recognition Challenge](https://mlsanity.com/paper/1409.0575/) (2014)
- [Deep Sets](https://mlsanity.com/paper/1703.06114/) (2017)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [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)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [Visual Domain Adaptation with Manifold Embedded Distribution Alignment](https://mlsanity.com/paper/1807.07258/) (2018)
- [Interventional Bag Multi-Instance Learning On Whole-Slide Pathological Images](https://mlsanity.com/paper/2303.06873/) (2023)
- [Morphological Prototyping for Unsupervised Slide Representation Learning in Computational Pathology](https://mlsanity.com/paper/2405.11643/) (2024)
- [Feature Re-Embedding: Towards Foundation Model-Level Performance in Computational Pathology](https://mlsanity.com/paper/2402.17228/) (2024)
- [Attention-Challenging Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2311.07125/) (2023)
- [Pathologist-level classification of histologic patterns on resected lung adenocarcinoma slides with deep neural networks](https://mlsanity.com/paper/1901.11489/) (2019)
- [Structured State Space Models for Multiple Instance Learning in Digital Pathology](https://mlsanity.com/paper/2306.15789/) (2023)
- [DGR-MIL: Exploring Diverse Global Representation in Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2407.03575/) (2024)
- [Improving Representation Learning for Histopathologic Images with Cluster Constraints](https://mlsanity.com/paper/2310.12334/) (2023)
- [cDP-MIL: Robust Multiple Instance Learning via Cascaded Dirichlet Process](https://mlsanity.com/paper/2407.11448/) (2024)

## Abstract (arXiv)

Whole slide images (WSIs) are the gold standard for pathological diagnosis and sub-typing. Current main-stream two-step frameworks employ offline feature encoders trained without domain-specific knowledge. Among them, attention-based multiple instance learning (MIL) methods are outcome-oriented and offer limited interpretability. Clustering-based approaches can provide explainable decision-making process but suffer from high dimension features and semantically ambiguous centroids. To this end, we propose an end-to-end MIL framework that integrates Grassmann re-embedding and manifold adaptive clustering, where the manifold geometric structure facilitates robust clustering results. Furthermore, we design a prior knowledge guiding proxy instance labeling and aggregation strategy to approximate patch labels and focus on pathologically relevant tumor regions. Experiments on multicentre WSI datasets demonstrate that: 1) our cluster-incorporated model achieves superior performance in both grading accuracy and interpretability; 2) end-to-end learning refines better feature representations and it requires acceptable computation resources.