# Hierarchical Graph Representations in Digital Pathology

arXiv: https://arxiv.org/abs/2102.11057 · HTML: https://mlsanity.com/paper/2102.11057/

## Key facts

- Cited by 59 papers in the map (data through 14 Oct 2026).
- Builds on 41 of its 90 references that are in the map.
- First posted on arXiv 22 Feb 2021.

## Builds on (most cited first, 30 of 41)

- [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)
- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [Inductive Representation Learning on Large Graphs](https://mlsanity.com/paper/1706.02216/) (2017)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [Neural Message Passing for Quantum Chemistry](https://mlsanity.com/paper/1704.01212/) (2017)
- [Convolutional Neural Networks on Graphs with Fast Localized Spectral Filtering](https://mlsanity.com/paper/1606.09375/) (2016)
- [A Survey on Deep Learning in Medical Image Analysis](https://mlsanity.com/paper/1702.05747/) (2017)
- [Weisfeiler and Leman Go Neural: Higher-order Graph Neural Networks](https://mlsanity.com/paper/1810.02244/) (2018)
- [Representation Learning on Graphs with Jumping Knowledge Networks](https://mlsanity.com/paper/1806.03536/) (2018)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [Benchmarking Graph Neural Networks](https://mlsanity.com/paper/2003.00982/) (2020)
- [Principal Neighbourhood Aggregation for Graph Nets](https://mlsanity.com/paper/2004.05718/) (2020)
- [HoVer-Net: Simultaneous Segmentation and Classification of Nuclei in Multi-Tissue Histology Images](https://mlsanity.com/paper/1812.06499/) (2018)
- [Deep Graph Library: A Graph-Centric, Highly-Performant Package for Graph Neural Networks](https://mlsanity.com/paper/1909.01315/) (2019)
- [Whole Slide Images based Cancer Survival Prediction using Attention Guided Deep Multiple Instance Learning Networks](https://mlsanity.com/paper/2009.11169/) (2020)
- [Quantifying the effects of data augmentation and stain color normalization in convolutional neural networks for computational pathology](https://mlsanity.com/paper/1902.06543/) (2019)
- [Pathomic Fusion: An Integrated Framework for Fusing Histopathology and Genomic Features for Cancer Diagnosis and Prognosis](https://mlsanity.com/paper/1912.08937/) (2019)
- [Deep neural network models for computational histopathology: A survey](https://mlsanity.com/paper/1912.12378/) (2019)
- [BACH: Grand Challenge on Breast Cancer Histology Images](https://mlsanity.com/paper/1808.04277/) (2018)
- [MILD-Net: Minimal Information Loss Dilated Network for Gland Instance Segmentation in Colon Histology Images](https://mlsanity.com/paper/1806.01963/) (2018)
- [Machine learning methods for histopathological image analysis](https://mlsanity.com/paper/1709.00786/) (2017)
- [Superpixel Sampling Networks](https://mlsanity.com/paper/1807.10174/) (2018)
- [Neural Image Compression for Gigapixel Histopathology Image Analysis](https://mlsanity.com/paper/1811.02840/) (2018)
- [CGC-Net: Cell Graph Convolutional Network for Grading of Colorectal Cancer Histology Images](https://mlsanity.com/paper/1909.01068/) (2019)
- [Understanding the Representation Power of Graph Neural Networks in Learning Graph Topology](https://mlsanity.com/paper/1907.05008/) (2019)
- [Streaming convolutional neural networks for end-to-end learning with multi-megapixel images](https://mlsanity.com/paper/1911.04432/) (2019)
- [Representation Learning of Histopathology Images using Graph Neural Networks](https://mlsanity.com/paper/2004.07399/) (2020)

## Built on by (most cited first, 30 of 59)

- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [Visual Language Pretrained Multiple Instance Zero-Shot Transfer for Histopathology Images](https://mlsanity.com/paper/2306.07831/) (2023)
- [BRACS: A Dataset for BReAst Carcinoma Subtyping in H&E Histology Images](https://mlsanity.com/paper/2111.04740/) (2021)
- [Artificial Intelligence for Digital and Computational Pathology](https://mlsanity.com/paper/2401.06148/) (2023)
- [Dynamic Graph Representation with Knowledge-aware Attention for Histopathology Whole Slide Image Analysis](https://mlsanity.com/paper/2403.07719/) (2024)
- [Differentiable Zooming for Multiple Instance Learning on Whole-Slide Images](https://mlsanity.com/paper/2204.12454/) (2022)
- [A General-Purpose Self-Supervised Model for Computational Pathology](https://mlsanity.com/paper/2308.15474/) (2023)
- [Evidence-based diagnostic reasoning with multi-agent copilot for human pathology](https://mlsanity.com/paper/2506.20964/) (2025)
- [ConSlide: Asynchronous Hierarchical Interaction Transformer with Breakup-Reorganize Rehearsal for Continual Whole Slide Image Analysis](https://mlsanity.com/paper/2308.13324/) (2023)
- [ScoreNet: Learning Non-Uniform Attention and Augmentation for Transformer-Based Histopathological Image Classification](https://mlsanity.com/paper/2202.07570/) (2022)
- [HistoCartography: A Toolkit for Graph Analytics in Digital Pathology](https://mlsanity.com/paper/2107.10073/) (2021)
- [AMIGO: Sparse Multi-Modal Graph Transformer with Shared-Context Processing for Representation Learning of Giga-pixel Images](https://mlsanity.com/paper/2303.00865/) (2023)
- [Pan-tumor CAnine cuTaneous Cancer Histology (CATCH) dataset](https://mlsanity.com/paper/2201.11446/) (2022)
- [Structure Embedded Nucleus Classification for Histopathology Images](https://mlsanity.com/paper/2302.11416/) (2023)
- [Interpretable Vision-Language Survival Analysis with Ordinal Inductive Bias for Computational Pathology](https://mlsanity.com/paper/2409.09369/) (2024)
- [Graph Neural Networks in Histopathology: Emerging Trends and Future Directions](https://mlsanity.com/paper/2406.12808/) (2024)
- [Shapley Values-enabled Progressive Pseudo Bag Augmentation for Whole Slide Image Classification](https://mlsanity.com/paper/2312.05490/) (2023)
- [DSCA: A Dual-Stream Network with Cross-Attention on Whole-Slide Image Pyramids for Cancer Prognosis](https://mlsanity.com/paper/2206.05782/) (2022)
- [Weakly Supervised Joint Whole-Slide Segmentation and Classification in Prostate Cancer](https://mlsanity.com/paper/2301.02933/) (2023)
- [Cell Graph Transformer for Nuclei Classification](https://mlsanity.com/paper/2402.12946/) (2024)
- [Tissue Concepts: supervised foundation models in computational pathology](https://mlsanity.com/paper/2409.03519/) (2024)
- [Multi-Scale Relational Graph Convolutional Network for Multiple Instance Learning in Histopathology Images](https://mlsanity.com/paper/2212.08781/) (2022)
- [Multi-scale Feature Alignment for Continual Learning of Unlabeled Domains](https://mlsanity.com/paper/2302.01287/) (2023)
- [Efficient Parameter Optimisation for Quantum Kernel Alignment: A Sub-sampling Approach in Variational Training](https://mlsanity.com/paper/2401.02879/) (2024)
- [From Graphs to Qubits: A Critical Review of Quantum Graph Neural Networks](https://mlsanity.com/paper/2408.06524/) (2024)
- [Multi-scale Efficient Graph-Transformer for Whole Slide Image Classification](https://mlsanity.com/paper/2305.15773/) (2023)
- [Stain-invariant self supervised learning for histopathology image analysis](https://mlsanity.com/paper/2211.07590/) (2022)
- [DIOR-ViT: Differential Ordinal Learning Vision Transformer for Cancer Classification in Pathology Images](https://mlsanity.com/paper/2407.08503/) (2024)
- [Hybrid Graph: A Unified Graph Representation with Datasets and Benchmarks for Complex Graphs](https://mlsanity.com/paper/2306.05108/) (2023)
- [Heterogeneous graphs model spatial relationships between biological entities for breast cancer diagnosis](https://mlsanity.com/paper/2307.08132/) (2023)

## Abstract (arXiv)

Cancer diagnosis, prognosis, and therapy response predictions from tissue specimens highly depend on the phenotype and topological distribution of constituting histological entities. Thus, adequate tissue representations for encoding histological entities is imperative for computer aided cancer patient care. To this end, several approaches have leveraged cell-graphs that encode cell morphology and organization to denote the tissue information. These allow for utilizing machine learning to map tissue representations to tissue functionality to help quantify their relationship. Though cellular information is crucial, it is incomplete alone to comprehensively characterize complex tissue structure. We herein treat the tissue as a hierarchical composition of multiple types of histological entities from fine to coarse level, capturing multivariate tissue information at multiple levels. We propose a novel multi-level hierarchical entity-graph representation of tissue specimens to model hierarchical compositions that encode histological entities as well as their intra- and inter-entity level interactions. Subsequently, a graph neural network is proposed to operate on the hierarchical entity-graph representation to map the tissue structure to tissue functionality. Specifically, for input histology images we utilize well-defined cells and tissue regions to build HierArchical Cell-to-Tissue (HACT) graph representations, and devise HACT-Net, a graph neural network, to classify such HACT representations. As part of this work, we introduce the BReAst Carcinoma Subtyping (BRACS) dataset, a large cohort of H&E stained breast tumor images, to evaluate our proposed methodology against pathologists and state-of-the-art approaches. Through comparative assessment and ablation studies, our method is demonstrated to yield superior classification results compared to alternative methods as well as pathologists.