• Huan Yang, Lili Chen, Zhiqiang Cheng, Minglei Yang, Jianbo Wang, Chenghao Lin, Yuefeng Wang, Leilei Huang, Yangshan Chen, Sui Peng, Zunfu Ke, and Weizhong Li.
• Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
• Bmc Med. 2021 Mar 29; 19 (1): 80.

BackgroundTargeted therapy and immunotherapy put forward higher demands for accurate lung cancer classification, as well as benign versus malignant disease discrimination. Digital whole slide images (WSIs) witnessed the transition from traditional histopathology to computational approaches, arousing a hype of deep learning methods for histopathological analysis. We aimed at exploring the potential of deep learning models in the identification of lung cancer subtypes and cancer mimics from WSIs.MethodsWe initially obtained 741 WSIs from the First Affiliated Hospital of Sun Yat-sen University (SYSUFH) for the deep learning model development, optimization, and verification. Additional 318 WSIs from SYSUFH, 212 from Shenzhen People's Hospital, and 422 from The Cancer Genome Atlas were further collected for multi-centre verification. EfficientNet-B5- and ResNet-50-based deep learning methods were developed and compared using the metrics of recall, precision, F1-score, and areas under the curve (AUCs). A threshold-based tumour-first aggregation approach was proposed and implemented for the label inferencing of WSIs with complex tissue components. Four pathologists of different levels from SYSUFH reviewed all the testing slides blindly, and the diagnosing results were used for quantitative comparisons with the best performing deep learning model.ResultsWe developed the first deep learning-based six-type classifier for histopathological WSI classification of lung adenocarcinoma, lung squamous cell carcinoma, small cell lung carcinoma, pulmonary tuberculosis, organizing pneumonia, and normal lung. The EfficientNet-B5-based model outperformed ResNet-50 and was selected as the backbone in the classifier. Tested on 1067 slides from four cohorts of different medical centres, AUCs of 0.970, 0.918, 0.963, and 0.978 were achieved, respectively. The classifier achieved high consistence to the ground truth and attending pathologists with high intraclass correlation coefficients over 0.873.ConclusionsMulti-cohort testing demonstrated our six-type classifier achieved consistent and comparable performance to experienced pathologists and gained advantages over other existing computational methods. The visualization of prediction heatmap improved the model interpretability intuitively. The classifier with the threshold-based tumour-first label inferencing method exhibited excellent accuracy and feasibility in classifying lung cancers and confused nonneoplastic tissues, indicating that deep learning can resolve complex multi-class tissue classification that conforms to real-world histopathological scenarios.

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