Christian Grashei

Oskar Thaeter, Christian Grashei, Anette Haas et al.

Stains are essential in histopathology to visualize specific tissue characteristics, with Haematoxylin and Eosin (H&E) serving as the clinical standard. However, pathologists frequently utilize a variety of special stains for the diagnosis of specific morphologies. Maintaining accurate metadata for these slides is critical for quality control in clinical archives and for the integrity of computational pathology datasets. In this work, we compare two approaches for automated classification of stains using whole slide images, covering the 14 most commonly used special stains in our institute alongside standard and frozen-section H&E. We evaluate a Multi-Instance Learning (MIL) pipeline and a proposed lightweight thumbnail-based approach. On internal test data, MIL achieved the highest performance (macro F1: 0.941 for 16 classes; 0.969 for 14 merged classes), while the thumbnail approach remained competitive (0.897 and 0.953, respectively). On external TCGA data, the thumbnail model generalized best (weighted F1: 0.843 vs. 0.807 for MIL). The thumbnail approach also increased throughput by two orders of magnitude (5.635 vs. 0.018 slides/s for MIL with all patches). We conclude that thumbnail-based classification provides a scalable and robust solution for routine visual quality control in digital pathology workflows.

Christian Grashei, Christian Brechenmacher, Rao Muhammad Umer et al.

Pathology foundation models (FMs) have driven significant progress in computational pathology. However, these high-performing models can easily exceed a billion parameters and produce high-dimensional embeddings, thus limiting their applicability for research or clinical use when computing resources are tight. Here, we introduce Pathryoshka, a multi-teacher distillation framework inspired by RADIO distillation and Matryoshka Representation Learning to reduce pathology FM sizes while allowing for adaptable embedding dimensions. We evaluate our framework with a distilled model on ten public pathology benchmarks with varying downstream tasks. Compared to its much larger teachers, Pathryoshka reduces the model size by 86-92% at on-par performance. It outperforms state-of-the-art single-teacher distillation models of comparable size by a median margin of 7.0 in accuracy. By enabling efficient local deployment without sacrificing accuracy or representational richness, Pathryoshka democratizes access to state-of-the-art pathology FMs for the broader research and clinical community.

Jingsong Liu, Xiaofeng Deng, Han Li et al.

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.