PathoS2VD: From 2D Histopathology to Pseudo Z-Stack Representations

Jiamu Wang, Keunho Byeon, Ji-Uk Kim, Jin Tae Kwak, Heounjeong Go

For decades, diagnostic pathology has relied on thin two-dimensional (2D) tissue sections, despite biological tissues exhibiting inherently three-dimensional (3D) morphological organization. Because a single section captures only one focal plane, important morphological cues along the z-axis are inevitably discarded, limiting tissue representation for both human interpretation and computational analysis. In this work, we propose a generative framework that learns z-axis morphological priors from pathology z-stack data, offering a cost-effective alternative to dedicated volumetric imaging, and transfers this knowledge to conventional single-plane histopathology. Specifically, an image-to-video (I2V) latent diffusion model (LDM) is trained to synthesize a pseudo z-stack from a single 2D image, capturing plausible morphological variations across adjacent focal planes rather than reconstructing physical tissue volumes. To enable deployment on large-scale clinical datasets without native z-stack acquisition, we further introduce a prior-preserving mixture fine-tuning strategy that adapts the model to new domains while retaining the learned z-axis morphological prior. Extensive…