Deep learning shows the capability of high-level computer-aided diagnosis in malignant lymphoma

Abstract

A pathological evaluation is one of the most important methods for the diagnosis of malignant lymphoma. A standardized diagnosis is occasionally difficult to achieve even by experienced hematopathologists. Therefore, established procedures including a computer-aided diagnosis are desired. This study aims to classify histopathological images of malignant lymphomas through deep learning, which is a computer algorithm and type of artificial intelligence (AI) technology. We prepared hematoxylin and eosin (H&E) slides of a lesion area from 388 sections, namely, 259 with diffuse large B-cell lymphoma, 89 with follicular lymphoma, and 40 with reactive lymphoid hyperplasia, and created whole slide images (WSIs) using a whole slide system. WSI was annotated in the lesion area by experienced hematopathologists. Image patches were cropped from the WSI to train and evaluate the classifiers. Image patches at magnifications of ×5, ×20, and ×40 were randomly divided into a test set and a training and evaluation set. The classifier was assessed using the test set through a cross-validation after training. The classifier achieved the highest levels of accuracy of 94.0%, 93.0%, and 92.0% for image patches with magnifications of ×5, ×20, and ×40, respectively, in comparison to diffuse large B-cell lymphoma, follicular lymphoma, and reactive lymphoid hyperplasia. Comparing the diagnostic accuracies between the proposed classifier and seven pathologists, including experienced hematopathologists, using the test set made up of image patches with magnifications of ×5, ×20, and ×40, the best accuracy demonstrated by the classifier was 97.0%, whereas the average accuracy achieved by the pathologists using WSIs was 76.0%, with the highest accuracy reaching 83.3%. In conclusion, the neural classifier can outperform pathologists in a morphological evaluation. These results suggest that the AI system can potentially support the diagnosis of malignant lymphoma.

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Fig. 1: Procedure for creating image patches.
Fig. 2: Preprocess during the training and testing phase.
Fig. 3: Examples of image patches.
Fig. 4: Deep neural network classifier used in this study.
Fig. 5: Examples of predicted images.
Fig. 6: Receiver operating characteristic curves of cross-validation.
Fig. 7: Model ensemble.
Fig. 8: ROC curves of the ensembled classifier as compared with the diagnosis of the pathologists.
Fig. 9: Confusion matrices of classifiers and pathologists.

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Acknowledgements

Chugai Pharmaceutical Co., Ltd provided funding for this study based on a joint research contract.

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Correspondence to Hiroaki Miyoshi.

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Miyoshi, H., Sato, K., Kabeya, Y. et al. Deep learning shows the capability of high-level computer-aided diagnosis in malignant lymphoma. Lab Invest 100, 1300–1310 (2020). https://doi.org/10.1038/s41374-020-0442-3

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