ContiStain: Cross-Domain Relation-Preserving Distillation for Continual Multi-Domain Virtual IHC Staining

Abstract: A unified multiplex virtual staining model enables scalable and non-destructive multiplex analysis from H&E slides while promoting parameter efficiency, shared pathological knowledge, and consistent cross-biomarker representations. However, in clinical practice, data for new biomarkers are typically acquired sequentially over time. Fine-tuning on such temporally arriving data leads to severe performance degradation on previously learned biomarkers, as sequential optimization disrupts the structured relationships among biomarker representations in the latent space. To address this issue, we propose ContiStain, an IHC multi-domain relational distillation framework for continual virtual staining. We first (i) construct a domain-aware structured feature space using a mixture-of-experts (MoE) feature extractor to reduce representation interference across biomarker domains. Based on this stabilized feature space, we then (ii) propose a relation-preserving distillation strategy that explicitly enforces the consistency of cross-domain token-level cosine similarity matrices between learned biomarker domains during continual adaptation. By maintaining cross-domain structural coherence, ContiStain mitigates forgetting while retaining adaptability to new domains. Experiments on the MIST dataset under a four-domain sequential virtual IHC staining setting show improved stability, reducing FID and ConchFID by 11.1 and 60.9 compared to sequential fine-tuning, enabling scalable and robust multi-domain virtual staining. Code is released at https://github.com/ccitachi/ContiStain.