BioX-CPath: Biologically-driven Explainable Diagnostics for Multistain IHC Computational Pathology

The development of biologically interpretable and explainable models remains a key challenge in computational pathology, particularly for multistain immunohistochemistry (IHC) analysis. We present BioX-CPath, an explainable graph neural network architecture for whole slide image (WSI) classification that leverages both spatial and semantic features across multiple stains. At its core, BioX-CPath introduces a novel Stain-Aware Attention Pooling (SAAP) module that generates biologically meaningful, stain-aware patient embeddings. Our approach achieves state-of-the-art performance on both Rheumatoid Arthritis and Sjogren's Disease multistain datasets. Beyond performance metrics, BioX-CPath provides interpretable insights through stain attention scores, entropy measures, and stain interaction scores, that permit measuring model alignment with known pathological mechanisms. This biological grounding, combined with strong classification performance, makes BioX-CPath particularly suitable for clinical applications where interpretability is key. Source code and documentation can be found at: https://github.com/AmayaGS/BioX-CPath.

Going Beyond H&E and Oncology: How Do Histopathology Foundation Models Perform for Multi-stain IHC and Immunology?

This study evaluates the generalisation capabilities of state-of-the-art histopathology foundation models on out-of-distribution multi-stain autoimmune Immunohistochemistry datasets. We compare 13 feature extractor models, including ImageNet-pretrained networks, and histopathology foundation models trained on both public and proprietary data, on Rheumatoid Arthritis subtyping and Sjogren's Disease detection tasks. Using a simple Attention-Based Multiple Instance Learning classifier, we assess the transferability of learned representations from cancer H&E images to autoimmune IHC images. Contrary to expectations, histopathology-pretrained models did not significantly outperform ImageNet-pretrained models. Furthermore, there was evidence of both autoimmune feature misinterpretation and biased feature importance. Our findings highlight the challenges in transferring knowledge from cancer to autoimmune histopathology and emphasise the need for careful evaluation of AI models across diverse histopathological tasks. The code to run this benchmark is available at https://github.com/AmayaGS/ImmunoHistoBench.