AUTHOR=Wang Linyan , Jiang Zijing , Shao An , Liu Zhengyun , Gu Renshu , Ge Ruiquan , Jia Gangyong , Wang Yaqi , Ye Juan TITLE=Self-supervised learning mechanism for identification of eyelid malignant melanoma in pathologic slides with limited annotation JOURNAL=Frontiers in Medicine VOLUME=Volume 9 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.976467 DOI=10.3389/fmed.2022.976467 ISSN=2296-858X ABSTRACT=Purpose:Lack of fine annotated pathologic data has limited the application of deep learning systems (DLS) to the automated interpretation of pathologic slides. Herein, we develop a robust self-supervised learning (SSL) pathology diagnostic system to automatically detect malignant melanoma (MM) in the eyelid with limited annotation. Design: Development of a self-supervised diagnosis pipeline based on public dataset, then refined and tested in private real clinical dataset. Subjects: A. Patchcamelyon (PCam)-a publicly accessible dataset for the classification task of patch-level histopathologic images. B. The Second Affiliated Hospital, Zhejiang University School of Medicine (ZJU-2) dataset - 524307 patches (small sections cut from pathologic slide images) from 192 H&E-stained whole-slide-images (WSIs); only 72 WSIs were labeled by pathologists. Methods: PCam was used to select a convolutional neural network (CNN) as the backbone for our SSL-based model. This model was further developed in ZJU-2 dataset for patch-level classification with both labeled and unlabeled images to test its diagnosis ability. Then the algorithm retrieved information based on patch-level prediction to generate WSI-level classification results using random forest. A heatmap was computed for visualizing decision-making process. Main outcome measure(s): The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity were used to evaluate the performance of the algorithm in identifying MM. Results:ResNet50 was selected as the backbone of SSL-based model using PCam dataset. This algorithm then achieved an AUC of 0.981, with the accuracy, sensitivity, specificity of 90.9%, 85.2%, 96.3% for patch-level classification of ZJU-2 dataset. For WSI-level diagnosis, the AUC, accuracy, sensitivity, specificity was 0.974, 93.8%, 75.0%, 100% separately. For every WSI, a heatmap was generated based on the malignancy probability. Conclusions: Our diagnostic system, which is based on SSL and trained with dataset of limited annotation, can automatically identify MM in pathologic slides and highlight MM area in WSIs by a probabilistic heatmap. In addition, this laborsaving and cost-efficient model has the potential to be refined to help diagnose with other ophthalmic and non-ophthalmic malignancies.