Enabling clinical use of foundation models in histopathology

Audun L. Henriksen, Ole-Johan Skrede, Lisa van der Schee, Enric Domingo, Sepp De Raedt +29 more
2/25/2026
cs.CVcs.AI

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Abstract

Foundation models in histopathology are expected to facilitate the development of high-performing and generalisable deep learning systems. However, current models capture not only biologically relevant features, but also pre-analytic and scanner-specific variation that bias the predictions of task-specific models trained from the foundation model features. Here we show that introducing novel robustness losses during training of downstream task-specific models reduces sensitivity to technical variability. A purpose-designed comprehensive experimentation setup with 27,042 WSIs from 6155 patients is used to train thousands of models from the features of eight popular foundation models for computational pathology. In addition to a substantial improvement in robustness, we observe that prediction accuracy improves by focusing on biologically relevant features. Our approach successfully mitigates robustness issues of foundation models for computational pathology without retraining the foundation models themselves, enabling development of robust computational pathology models applicable to real-world data in routine clinical practice.

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@article{henriksen2026enabling,
  title  = {Enabling clinical use of foundation models in histopathology},
  author = {Audun L. Henriksen and Ole-Johan Skrede and Lisa van der Schee and Enric Domingo and Sepp De Raedt and Ilyá Kostolomov and Jennifer Hay and Karolina Cyll and Wanja Kildal and Joakim Kalsnes and Robert W. Williams and Manohar Pradhan and John Arne Nesheim and Hanne A. Askautrud and Maria X. Isaksen and Karmele Saez de Gordoa and Miriam Cuatrecasas and Joanne Edwards and TransSCOT group and Arild Nesbakken and Neil A. Shepherd and Ian Tomlinson and Daniel-Christoph Wagner and Rachel S. Kerr and Tarjei Sveinsgjerd Hveem and Knut Liestøl and Yoshiaki Nakamura and Marco Novelli and Masaaki Miyo and Sebastian Foersch and David N. Church and Miangela M. Lacle and David J. Kerr and Andreas Kleppe},
  year   = {2026},
  eprint = {2602.22347},
  archivePrefix = {arXiv},
  url    = {http://arxiv.org/abs/2602.22347v1}
}

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