Hidden Variables in Deep Learning Digital Pathology and Their Potential to Cause Batch Effects: Prediction Model Study

Max Schmitt   ^{1 *} , MSc ;   Roman Christoph Maron   ^{1 *} , MSc ;   Achim Hekler   ¹ , MSc ;   Albrecht Stenzinger   ² , MD ;   Axel Hauschild   ³ , MD ;   Michael Weichenthal   ³ , MD ;   Markus Tiemann   ⁴ , MD ;   Dieter Krahl   ⁵ , MD ;   Heinz Kutzner   ⁶ , MD ;   Jochen Sven Utikal   ^{7, 8} , MD ;   Sebastian Haferkamp   ⁹ , MD ;   Jakob Nikolas Kather   ¹⁰ , MD ;   Frederick Klauschen   ¹¹ , MD ;   Eva Krieghoff-Henning   ¹ , PhD ;   Stefan Fröhling   ¹² , MD ;   Christof von Kalle   ¹³ , MD ;   Titus Josef Brinker   ¹ , MD

¹ Digital Biomarkers for Oncology Group, National Center for Tumor Diseases, German Cancer Research Center (DKFZ), Heidelberg, Germany

² Institute of Pathology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany

³ Department of Dermatology, University Hospital Kiel, University of Kiel, Kiel, Germany

⁴ Institute for Hematopathology Hamburg, Hamburg, Germany

⁵ Private Institute of Dermatopathology, Heidelberg, Germany

⁶ Private Institute of Dermatopathology, Friedrichshafen, Germany

⁷ Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany

⁸ Department of Dermatology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany

⁹ Department of Dermatology, University Hospital of Regensburg, Regensburg, Germany

¹⁰ Department of Medicine III, RWTH University Hospital Aachen, Aachen, Germany

¹¹ Institute of Pathology, Charité University Hospital Berlin, Berlin, Germany

¹² National Center for Tumor Diseases, German Cancer Research Center (DKFZ), Heidelberg, Germany

¹³ Department of Clinical-Translational Sciences, Charité and Berlin Institute of Health, Berlin, Germany

*these authors contributed equally