From Pixels to Pathology: Restoration Diffusion for Diagnostic-Consistent Virtual IHC

Jingsong Liu; Xiaofeng Deng; Han Li; Azar Kazemi; Christian Grashei; Gesa Wilkens; Xin You; Tanja Groll; Nassir Navab; Carolin Mogler; Peter J. Schüffler

arXiv · 2508.02528

From Pixels to Pathology: Restoration Diffusion for Diagnostic-Consistent Virtual IHC

Jingsong Liu·Xiaofeng Deng·Han Li·Azar Kazemi·Christian Grashei·Gesa Wilkens·Xin You·Tanja Groll·Nassir Navab·Carolin Mogler·Peter J. Schüffler

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Abstract

Hematoxylin and eosin (H&E) staining is the clinical standard for assessing tissue morphology, but it lacks molecular-level diagnostic information. In contrast, immunohistochemistry (IHC) provides crucial insights into biomarker expression, such as HER2 status for breast cancer grading, but remains costly and time-consuming, limiting its use in time-sensitive clinical workflows. To address this gap, virtual staining from H&E to IHC has emerged as a promising alternative, yet faces two core challenges: (1) Lack of fair evaluation of synthetic images against misaligned IHC ground truths, and (2) preserving structural integrity and biological variability during translation. To this end, we present an end-to-end framework encompassing both generation and evaluation in this work. We introduce Star-Diff, a structure-aware staining restoration diffusion model that reformulates virtual staining as an image restoration task. By combining residual and noise-based generation pathways, Star-Diff maintains tissue structure while modeling realistic biomarker variability. To evaluate the diagnostic consistency of the generated IHC patches, we propose the Semantic Fidelity Score (SFS), a clinical-grading-task-driven metric that quantifies class-wise semantic degradation based on biomarker classification accuracy. Unlike pixel-level metrics such as SSIM and PSNR, SFS remains robust under spatial misalignment and classifier uncertainty. Experiments on the BCI dataset demonstrate that Star-Diff achieves state-of-the-art (SOTA) performance in both visual fidelity and diagnostic relevance. With rapid inference and strong clinical alignment,it presents a practical solution for applications such as intraoperative virtual IHC synthesis.

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Jingsong Liu, Xiaofeng Deng, Han Li, Azar Kazemi, Christian Grashei, Gesa Wilkens, Xin You, Tanja Groll, Nassir Navab, Carolin Mogler, Peter J. Schüffler. 2025-08-04. From Pixels to Pathology: Restoration Diffusion for Diagnostic-Consistent Virtual IHC. https://arxiv.org/abs/2508.02528

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