His‐MMDM: Multi‐Domain and Multi‐Omics Translation of Histopathological Images with Diffusion Models

Generative AI (GenAI) has advanced computational pathology through various image translation models. These models synthesize histopathological images from existing ones, facilitating tasks such as color normalization and virtual staining. Current models, while effective, are mostly dedicated to specific source-target domain pairs and lack scalability for multi-domain translations. Here, we introduce His-MMDM, a diffusion model-based framework enabling multi-domain and multi-omics histopathological image translation. His-MMDM is not only effective in performing existing tasks such as transforming cryosectioned images to FFPE ones and virtual immunohistochemical (IHC) staining but can also facilitate knowledge transfer between different tumor types and between primary and metastatic tumors. Additionally, it performs genomics- and/or transcriptomics-guided editing of histopathological images, illustrating the impact of driver mutations and oncogenic pathway alterations on tissue histopathology and educating pathologists to recognize them. These versatile capabilities position His-MMDM as a versatile tool in the GenAI toolkit for future pathologists.