Searching for Robust Augmentations to Improve Out-of-Domain Generalization in Dermoscopic Skin Cancer Classification

Background/Objectives: Dermoscopic skin-lesion classifiers lose accuracy when images arrive from a new clinic or a new device. We asked which data augmentations reduce that loss, and measured the effect under a protocol that keeps policy selection separate from policy evaluation. Methods: A ConvNeXt-Large binary malignant-versus-non-malignant classifier was trained on six dermoscopic sources (25,903 images); HAM10000 and ISIC 2016-2020 were held out of training entirely. Single augmentations, photometric combinations and eleven composite policies were ranked on a development split of 1511 held-out images. The winning policy was then evaluated on a confirmation set of 8073 held-out images that took no part in that ranking and from which we removed every image sharing a lesion identifier with the training data and every image contributed by an institution represented in training. Both policies were retrained with four random seeds each and compared with an exact permutation test. Results: The mix policy raised confirmation-set ROC-AUC from 0.787 to 0.826 (+0.039; per-seed ranges 0.772-0.797 and 0.815-0.840, non-overlapping; exact permutation p=0.029), with the same direction on each contributing source. At matched sensitivity the gain is larger in clinical terms: specificity rose from 0.612 to 0.713 at a sensitivity of 0.80, and from 0.284 to 0.397 at a sensitivity of 0.95. In-domain ROC-AUC was preserved (0.938 to 0.941). On an independent clinical cohort acquired with a different device at a different institution (472 images, 22 malignant), performance was maintained (0.934 versus 0.930). Conclusions: Augmentations that model the physical causes of domain shift improve cross-source transfer at no cost to in-domain accuracy, and the improvement survives a selection-disjoint, contamination-free evaluation.