Computer-aided diagnosis in histopathological images of the endometrium using a convolutional neural network and attention mechanisms

Uterine cancer, also known as endometrial cancer, can seriously affect the female reproductive organs, and histopathological image analysis is the gold standard for diagnosing endometrial cancer. However, due to the limited capability of modeling the complicated relationships between histopathological images and their interpretations, these computer-aided diagnosis (CADx) approaches based on traditional machine learning algorithms often failed to achieve satisfying results. In this study, we developed a CADx approach using a convolutional neural network (CNN) and attention mechanisms, called HIENet. Because HIENet used the attention mechanisms and feature map visualization techniques, it can provide pathologists better interpretability of diagnoses by highlighting the histopathological correlations of local (pixel-level) image features to morphological characteristics of endometrial tissue. In the ten-fold cross-validation process, the CADx approach, HIENet, achieved a 76.91 $\pm$ 1.17% (mean $\pm$ s. d.) classification accuracy for four classes of endometrial tissue, namely normal endometrium, endometrial polyp, endometrial hyperplasia, and endometrial adenocarcinoma. Also, HIENet achieved an area-under-the-curve (AUC) of 0.9579 $\pm$ 0.0103 with an 81.04 $\pm$ 3.87% sensitivity and 94.78 $\pm$ 0.87% specificity in a binary classification task that detected endometrioid adenocarcinoma (Malignant). Besides, in the external validation process, HIENet achieved an 84.50% accuracy in the four-class classification task, and it achieved an AUC of 0.9829 with a 77.97% (95% CI, 65.27%-87.71%) sensitivity and 100% (95% CI, 97.42%-100.00%) specificity. In summary, the proposed CADx approach, HIENet, outperformed three human experts and four end-to-end CNN-based classifiers on this small-scale dataset composed of 3,500 hematoxylin and eosin (H&E) images regarding overall classification performance.