Deep learning (DL) has shown great potential in digital pathology applications. The robustness of a diagnostic DL-based solution is essential for safe clinical deployment. In this work we evaluate if adding uncertainty estimates for DL predictions in digital pathology could result in increased value for the clinical applications, by boosting the general predictive performance or by detecting mispredictions. We compare the effectiveness of model-integrated methods (MC dropout and Deep ensembles) with a model-agnostic approach (Test time augmentation, TTA). Moreover, four uncertainty metrics are compared. Our experiments focus on two domain shift scenarios: a shift to a different medical center and to an underrepresented subtype of cancer. Our results show that uncertainty estimates increase reliability by reducing a model's sensitivity to classification threshold selection as well as by detecting between 70\% and 90\% of the mispredictions done by the model. Overall, the deep ensembles method achieved the best performance closely followed by TTA.
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