# AI-based Anomaly Detection for Clinical-Grade Histopathological Diagnostics

arXiv: https://arxiv.org/abs/2406.14866 · HTML: https://mlsanity.com/paper/2406.14866/

## Key facts

- Cited by 8 papers in the map (data through 14 Oct 2026).
- Builds on 46 of its 93 references that are in the map.
- First posted on arXiv 21 Jun 2024.

## Builds on (most cited first, 30 of 46)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [Grad-CAM: Visual Explanations from Deep Networks via Gradient-based Localization](https://mlsanity.com/paper/1610.02391/) (2016)
- [Axiomatic Attribution for Deep Networks](https://mlsanity.com/paper/1703.01365/) (2017)
- [Deep Inside Convolutional Networks: Visualising Image Classification Models and Saliency Maps](https://mlsanity.com/paper/1312.6034/) (2013)
- [The Many Faces of Robustness: A Critical Analysis of Out-of-Distribution Generalization](https://mlsanity.com/paper/2006.16241/) (2020)
- [Unsupervised Representation Learning by Predicting Image Rotations](https://mlsanity.com/paper/1803.07728/) (2018)
- [Can You Trust Your Model's Uncertainty? Evaluating Predictive Uncertainty Under Dataset Shift](https://mlsanity.com/paper/1906.02530/) (2019)
- [Deep Anomaly Detection with Outlier Exposure](https://mlsanity.com/paper/1812.04606/) (2018)
- [Towards Total Recall in Industrial Anomaly Detection](https://mlsanity.com/paper/2106.08265/) (2021)
- [PaDiM: a Patch Distribution Modeling Framework for Anomaly Detection and Localization](https://mlsanity.com/paper/2011.08785/) (2020)
- [Unsupervised Anomaly Detection with Generative Adversarial Networks to Guide Marker Discovery](https://mlsanity.com/paper/1703.05921/) (2017)
- [CutPaste: Self-Supervised Learning for Anomaly Detection and Localization](https://mlsanity.com/paper/2104.04015/) (2021)
- [Using Self-Supervised Learning Can Improve Model Robustness and Uncertainty](https://mlsanity.com/paper/1906.12340/) (2019)
- [CSI: Novelty Detection via Contrastive Learning on Distributionally Shifted Instances](https://mlsanity.com/paper/2007.08176/) (2020)
- [A Unifying Review of Deep and Shallow Anomaly Detection](https://mlsanity.com/paper/2009.11732/) (2020)
- [SPot-the-Difference Self-Supervised Pre-training for Anomaly Detection and Segmentation](https://mlsanity.com/paper/2207.14315/) (2022)
- [Unmasking Clever Hans Predictors and Assessing What Machines Really Learn](https://mlsanity.com/paper/1902.10178/) (2019)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [Deep Semi-Supervised Anomaly Detection](https://mlsanity.com/paper/1906.02694/) (2019)
- [Deep Anomaly Detection Using Geometric Transformations](https://mlsanity.com/paper/1805.10917/) (2018)
- [PANDA: Adapting Pretrained Features for Anomaly Detection and Segmentation](https://mlsanity.com/paper/2010.05903/) (2020)
- [Deep Autoencoding Models for Unsupervised Anomaly Segmentation in Brain MR Images](https://mlsanity.com/paper/1804.04488/) (2018)
- [Self supervised contrastive learning for digital histopathology](https://mlsanity.com/paper/2011.13971/) (2020)
- [Learning and Evaluating Representations for Deep One-class Classification](https://mlsanity.com/paper/2011.02578/) (2020)
- [Explainable Deep One-Class Classification](https://mlsanity.com/paper/2007.01760/) (2020)
- [DROCC: Deep Robust One-Class Classification](https://mlsanity.com/paper/2002.12718/) (2020)
- [Natural Synthetic Anomalies for Self-Supervised Anomaly Detection and Localization](https://mlsanity.com/paper/2109.15222/) (2021)
- [Deep Nearest Neighbor Anomaly Detection](https://mlsanity.com/paper/2002.10445/) (2020)
- [Deep Learning-based Computational Pathology Predicts Origins for Cancers of Unknown Primary](https://mlsanity.com/paper/2006.13932/) (2020)

## Built on by (most cited first, 8 of 8)

- [Atlas: A Novel Pathology Foundation Model by Mayo Clinic, Charit'e, and Aignostics](https://mlsanity.com/paper/2501.05409/) (2025)
- [MeDi: Metadata-Guided Diffusion Models for Mitigating Biases in Tumor Classification](https://mlsanity.com/paper/2506.17140/) (2025)
- [Atlas 2 -- Foundation models for clinical deployment](https://mlsanity.com/paper/2601.05148/) (2026)
- [RELICT: A Replica Detection Framework for Medical Image Generation](https://mlsanity.com/paper/2502.17360/) (2025)
- [Normal and Abnormal Pathology Knowledge-Augmented Vision-Language Model for Anomaly Detection in Pathology Images](https://mlsanity.com/paper/2508.15256/) (2025)
- [Value bounds and Convergence Analysis for Averages of LRP attributions](https://mlsanity.com/paper/2509.08963/) (2025)
- [Toxicity Assessment in Preclinical Histopathology via Class-Aware Mahalanobis Distance for Known and Novel Anomalies](https://mlsanity.com/paper/2602.02124/) (2026)
- [HERO: Histology Encoder for Robust Representation in Oncology](https://mlsanity.com/paper/2609.35943/) (2026)

## Abstract (arXiv)

While previous studies have demonstrated the potential of AI to diagnose diseases in imaging data, clinical implementation is still lagging behind. This is partly because AI models require training with large numbers of examples only available for common diseases. In clinical reality, however, only few diseases are common, whereas the majority of diseases are less frequent (long-tail distribution). Current AI models overlook or misclassify these diseases. We propose a deep anomaly detection approach that only requires training data from common diseases to detect also all less frequent diseases. We collected two large real-world datasets of gastrointestinal biopsies, which are prototypical of the problem. Herein, the ten most common findings account for approximately 90% of cases, whereas the remaining 10% contained 56 disease entities, including many cancers. 17 million histological images from 5,423 cases were used for training and evaluation. Without any specific training for the diseases, our best-performing model reliably detected a broad spectrum of infrequent ("anomalous") pathologies with 95.0% (stomach) and 91.0% (colon) AUROC and generalized across scanners and hospitals. By design, the proposed anomaly detection can be expected to detect any pathological alteration in the diagnostic tail of gastrointestinal biopsies, including rare primary or metastatic cancers. This study establishes the first effective clinical application of AI-based anomaly detection in histopathology that can flag anomalous cases, facilitate case prioritization, reduce missed diagnoses and enhance the general safety of AI models, thereby driving AI adoption and automation in routine diagnostics and beyond.