Impact of variation in tissue staining and scanning devices on performance of pan-cancer AI models: a study of sarcoma and their mimics

Histopathological analysis is considered the gold standard for the diagnosis and prognostication of cancer. Recent advances in AI, driven by large-scale digitisation and pan-cancer foundation models, are opening new opportunities for clinical integration. However, it remains unclear how robust these foundation models are to real-world sources of variability, particularly in H&E staining and scanning protocols. In this study, we use soft tissue tumours, a rare and morphologically diverse tumour type, as a challenging test case to systematically investigate the colour-related robustness and generalisability of seven AI models. Controlled staining and scanning experiments were utilised to assess model performance across diverse real-world data sources. Foundation models, particularly UNI-v2, Virchow and TITAN, demonstrated encouraging robustness to staining and scanning variation, particularly when a small number of stain-varied slides were included in the training loop, highlighting their potential as adaptable and data-efficient tools for real-world digital pathology workflows.