# CytoSyn: a Foundation Diffusion Model for Histopathology -- Tech Report

arXiv: https://arxiv.org/abs/2603.18089 · HTML: https://mlsanity.com/paper/2603.18089/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Placed in Medical imaging and segmentation, one of 14 directions in Diffusion models.
- Builds on 34 of its 51 references that are in the map.
- First posted on arXiv 18 Mar 2026.

## Placed in

- Diffusion models / [Medical imaging and segmentation](https://mlsanity.com/diffusion/medical-imaging-and-segmentation/)

## Builds on (most cited first, 30 of 34)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Diffusion Models Beat GANs on Image Synthesis](https://mlsanity.com/paper/2105.05233/) (2021)
- [DINOv2: Learning Robust Visual Features without Supervision](https://mlsanity.com/paper/2304.07193/) (2023)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [Scalable Diffusion Models with Transformers](https://mlsanity.com/paper/2212.09748/) (2022)
- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Rethinking the Inception Architecture for Computer Vision](https://mlsanity.com/paper/1512.00567/) (2015)
- [Scaling Rectified Flow Transformers for High-Resolution Image Synthesis](https://mlsanity.com/paper/2403.03206/) (2024)
- [Generative Modeling by Estimating Gradients of the Data Distribution](https://mlsanity.com/paper/1907.05600/) (2019)
- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [Improved Precision and Recall Metric for Assessing Generative Models](https://mlsanity.com/paper/1904.06991/) (2019)
- [Stochastic Interpolants: A Unifying Framework for Flows and Diffusions](https://mlsanity.com/paper/2303.08797/) (2023)
- [SiT: Exploring Flow and Diffusion-based Generative Models with Scalable Interpolant Transformers](https://mlsanity.com/paper/2401.08740/) (2024)
- [Representation Alignment for Generation: Training Diffusion Transformers Is Easier Than You Think](https://mlsanity.com/paper/2410.06940/) (2024)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [REPA-E: Unlocking VAE for End-to-End Tuning with Latent Diffusion Transformers](https://mlsanity.com/paper/2504.10483/) (2025)
- [Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology](https://mlsanity.com/paper/2408.00738/) (2024)
- [HEST-1k: A Dataset for Spatial Transcriptomics and Histology Image Analysis](https://mlsanity.com/paper/2406.16192/) (2024)
- [Phikon-v2, A large and public feature extractor for biomarker prediction](https://mlsanity.com/paper/2409.09173/) (2024)
- [A Clinical Benchmark of Public Self-Supervised Pathology Foundation Models](https://mlsanity.com/paper/2407.06508/) (2024)
- [Benchmarking foundation models as feature extractors for weakly-supervised computational pathology](https://mlsanity.com/paper/2408.15823/) (2024)
- [Learned representation-guided diffusion models for large-image generation](https://mlsanity.com/paper/2312.07330/) (2023)
- [Distilling foundation models for robust and efficient models in digital pathology](https://mlsanity.com/paper/2501.16239/) (2025)
- [RandStainNA: Learning Stain-Agnostic Features from Histology Slides by Bridging Stain Augmentation and Normalization](https://mlsanity.com/paper/2206.12694/) (2022)
- [Feature Likelihood Divergence: Evaluating the Generalization of Generative Models Using Samples](https://mlsanity.com/paper/2302.04440/) (2023)
- [Training state-of-the-art pathology foundation models with orders of magnitude less data](https://mlsanity.com/paper/2504.05186/) (2025)
- [ZoomLDM: Latent Diffusion Model for multi-scale image generation](https://mlsanity.com/paper/2411.16969/) (2024)

## Built on by (most cited first, 1 of 1)

- [BigCell: Generating Gigapixel Whole-Slide Images](https://mlsanity.com/paper/2610.14261/) (2026)

## Abstract (arXiv)

Computational pathology has made significant progress in recent years, fueling advances in both fundamental disease understanding and clinically ready tools. This evolution is driven by the availability of large amounts of digitized slides and specialized deep learning methods and models. Multiple self-supervised foundation feature extractors have been developed, enabling downstream predictive applications from cell segmentation to tumor sub-typing and survival analysis. In contrast, generative foundation models designed specifically for histopathology remain scarce. Such models could address tasks that are beyond the capabilities of feature extractors, such as virtual staining. In this paper, we introduce CytoSyn, a state-of-the-art foundation latent diffusion model that enables the guided generation of highly realistic and diverse histopathology H&E-stained images, as shown in an extensive benchmark. We explored methodological improvements, training set scaling, sampling strategies and slide-level overfitting, culminating in the improved CytoSyn-v2, and compared our work to PixCell, a state-of-the-art model, in an in-depth manner. This comparison highlighted the strong sensitivity of both diffusion models and performance metrics to preprocessing-specific details such as JPEG compression. Our model has been trained on a dataset obtained from more than 10,000 TCGA diagnostic whole-slide images of 32 different cancer types. Despite being trained only on oncology slides, it maintains state-of-the-art performance generating inflammatory bowel disease images. To support the research community, we publicly release CytoSyn's weights, its training and validation datasets, and a sample of synthetic images in this repository: https://huggingface.co/Owkin-Bioptimus/CytoSyn.