# DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification

arXiv: https://arxiv.org/abs/2203.12081 · HTML: https://mlsanity.com/paper/2203.12081/

## Key facts

- Cited by 256 papers in the map (data through 14 Oct 2026).
- Placed in Distillation for medical imaging, one of 12 directions in Knowledge distillation.
- Builds on 31 of its 56 references that are in the map.
- First posted on arXiv 22 Mar 2022.

## Placed in

- Knowledge distillation / [Distillation for medical imaging](https://mlsanity.com/distill/distillation-for-medical-imaging/)

## Builds on (most cited first, 30 of 31)

- [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)
- [Grad-CAM: Visual Explanations from Deep Networks via Gradient-based Localization](https://mlsanity.com/paper/1610.02391/) (2016)
- [Learning Deep Features for Discriminative Localization](https://mlsanity.com/paper/1512.04150/) (2015)
- [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)
- [Seed, Expand and Constrain: Three Principles for Weakly-Supervised Image Segmentation](https://mlsanity.com/paper/1603.06098/) (2016)
- [Patch-based Convolutional Neural Network for Whole Slide Tissue Image Classification](https://mlsanity.com/paper/1504.07947/) (2015)
- [Revisiting Multiple Instance Neural Networks](https://mlsanity.com/paper/1610.02501/) (2016)
- [Deep Learning for Identifying Metastatic Breast Cancer](https://mlsanity.com/paper/1606.05718/) (2016)
- [Weakly-Supervised Semantic Segmentation by Iteratively Mining Common Object Features](https://mlsanity.com/paper/1806.04659/) (2018)
- [CAMEL: A Weakly Supervised Learning Framework for Histopathology Image Segmentation](https://mlsanity.com/paper/1908.10555/) (2019)
- [Neural Image Compression for Gigapixel Histopathology Image Analysis](https://mlsanity.com/paper/1811.02840/) (2018)
- [Cluster-to-Conquer: A Framework for End-to-End Multi-Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2103.10626/) (2021)
- [Weakly supervised multiple instance learning histopathological tumor segmentation](https://mlsanity.com/paper/2004.05024/) (2020)
- [Min-Entropy Latent Model for Weakly Supervised Object Detection](https://mlsanity.com/paper/1902.06057/) (2019)
- [Streaming convolutional neural networks for end-to-end learning with multi-megapixel images](https://mlsanity.com/paper/1911.04432/) (2019)
- [Spatial Uncertainty-Aware Semi-Supervised Crowd Counting](https://mlsanity.com/paper/2107.13271/) (2021)
- [Fully Convolutional Multi-Class Multiple Instance Learning](https://mlsanity.com/paper/1412.7144/) (2014)
- [Semi-Supervised Histology Classification using Deep Multiple Instance Learning and Contrastive Predictive Coding](https://mlsanity.com/paper/1910.10825/) (2019)
- [Deep Multi-instance Networks with Sparse Label Assignment for Whole Mammogram Classification](https://mlsanity.com/paper/1612.05968/) (2016)
- [Multiple instance learning with graph neural networks](https://mlsanity.com/paper/1906.04881/) (2019)
- [Zigzag Learning for Weakly Supervised Object Detection](https://mlsanity.com/paper/1804.09466/) (2018)
- [TS2C: Tight Box Mining with Surrounding Segmentation Context for Weakly Supervised Object Detection](https://mlsanity.com/paper/1807.04897/) (2018)
- [Predicting molecular phenotypes from histopathology images: a transcriptome-wide expression-morphology analysis in breast cancer](https://mlsanity.com/paper/2009.08917/) (2020)
- [Cancer Metastasis Detection With Neural Conditional Random Field](https://mlsanity.com/paper/1806.07064/) (2018)
- [Multi-Instance Multi-Scale CNN for Medical Image Classification](https://mlsanity.com/paper/1907.02413/) (2019)
- [CAM-loss: Towards Learning Spatially Discriminative Feature Representations](https://mlsanity.com/paper/2109.01359/) (2021)

## Built on by (most cited first, 30 of 256)

- [Visual Language Pretrained Multiple Instance Zero-Shot Transfer for Histopathology Images](https://mlsanity.com/paper/2306.07831/) (2023)
- [Interventional Bag Multi-Instance Learning On Whole-Slide Pathological Images](https://mlsanity.com/paper/2303.06873/) (2023)
- [MambaMIL: Enhancing Long Sequence Modeling with Sequence Reordering in Computational Pathology](https://mlsanity.com/paper/2403.06800/) (2024)
- [Multimodal Optimal Transport-based Co-Attention Transformer with Global Structure Consistency for Survival Prediction](https://mlsanity.com/paper/2306.08330/) (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)
- [Dynamic Graph Representation with Knowledge-aware Attention for Histopathology Whole Slide Image Analysis](https://mlsanity.com/paper/2403.07719/) (2024)
- [Attention-Challenging Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2311.07125/) (2023)
- [Multiple Instance Learning Framework with Masked Hard Instance Mining for Whole Slide Image Classification](https://mlsanity.com/paper/2307.15254/) (2023)
- [Multiple Instance Learning for Digital Pathology: A Review on the State-of-the-Art, Limitations & Future Potential](https://mlsanity.com/paper/2206.04425/) (2022)
- [Task-specific Fine-tuning via Variational Information Bottleneck for Weakly-supervised Pathology Whole Slide Image Classification](https://mlsanity.com/paper/2303.08446/) (2023)
- [Transcriptomics-guided Slide Representation Learning in Computational Pathology](https://mlsanity.com/paper/2405.11618/) (2024)
- [HistGen: Histopathology Report Generation via Local-Global Feature Encoding and Cross-modal Context Interaction](https://mlsanity.com/paper/2403.05396/) (2024)
- [The Rise of AI Language Pathologists: Exploring Two-level Prompt Learning for Few-shot Weakly-supervised Whole Slide Image Classification](https://mlsanity.com/paper/2305.17891/) (2023)
- [Distilling foundation models for robust and efficient models in digital pathology](https://mlsanity.com/paper/2501.16239/) (2025)
- [2DMamba: Efficient State Space Model for Image Representation with Applications on Giga-Pixel Whole Slide Image Classification](https://mlsanity.com/paper/2412.00678/) (2024)
- [WSI-VQA: Interpreting Whole Slide Images by Generative Visual Question Answering](https://mlsanity.com/paper/2407.05603/) (2024)
- [WsiCaption: Multiple Instance Generation of Pathology Reports for Gigapixel Whole-Slide Images](https://mlsanity.com/paper/2311.16480/) (2023)
- [Do Multiple Instance Learning Models Transfer?](https://mlsanity.com/paper/2506.09022/) (2025)
- [ViLa-MIL: Dual-scale Vision-Language Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2502.08391/) (2025)
- [Diagnose Like a Pathologist: Transformer-Enabled Hierarchical Attention-Guided Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2301.08125/) (2023)
- [Generalizable Whole Slide Image Classification with Fine-Grained Visual-Semantic Interaction](https://mlsanity.com/paper/2402.19326/) (2024)
- [MapDistill: Boosting Efficient Camera-based HD Map Construction via Camera-LiDAR Fusion Model Distillation](https://mlsanity.com/paper/2407.11682/) (2024)
- [ConSlide: Asynchronous Hierarchical Interaction Transformer with Breakup-Reorganize Rehearsal for Continual Whole Slide Image Analysis](https://mlsanity.com/paper/2308.13324/) (2023)
- [DGR-MIL: Exploring Diverse Global Representation in Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2407.03575/) (2024)
- [MoME: Mixture of Multimodal Experts for Cancer Survival Prediction](https://mlsanity.com/paper/2406.09696/) (2024)
- [Multiple Instance Learning via Iterative Self-Paced Supervised Contrastive Learning](https://mlsanity.com/paper/2210.09452/) (2022)
- [Rethinking Multiple Instance Learning for Whole Slide Image Classification: A Good Instance Classifier is All You Need](https://mlsanity.com/paper/2307.02249/) (2023)
- [CPLIP: Zero-Shot Learning for Histopathology with Comprehensive Vision-Language Alignment](https://mlsanity.com/paper/2406.05205/) (2024)
- [FOCUS: Knowledge-enhanced Adaptive Visual Compression for Few-shot Whole Slide Image Classification](https://mlsanity.com/paper/2411.14743/) (2024)

## Abstract (arXiv)

Multiple instance learning (MIL) has been increasingly used in the classification of histopathology whole slide images (WSIs). However, MIL approaches for this specific classification problem still face unique challenges, particularly those related to small sample cohorts. In these, there are limited number of WSI slides (bags), while the resolution of a single WSI is huge, which leads to a large number of patches (instances) cropped from this slide. To address this issue, we propose to virtually enlarge the number of bags by introducing the concept of pseudo-bags, on which a double-tier MIL framework is built to effectively use the intrinsic features. Besides, we also contribute to deriving the instance probability under the framework of attention-based MIL, and utilize the derivation to help construct and analyze the proposed framework. The proposed method outperforms other latest methods on the CAMELYON-16 by substantially large margins, and is also better in performance on the TCGA lung cancer dataset. The proposed framework is ready to be extended for wider MIL applications. The code is available at: https://github.com/hrzhang1123/DTFD-MIL