Interpretable multi-scale deep learning to detect malignancy in cell blocks and cytological smears of pleural effusion and identify aggressive endometrial cancer

Abstract

The pleura is a serous membrane that surrounds the surface of the lungs. The visceral surface secretes fluid into the serous cavity, while the parietal surface ensures that the fluid is properly absorbed. However, when this balance is disrupted, it leads to the formation of pleural Effusion. The most common malignant pleural effusion (MPE) caused by lung cancer or breast cancer, and benign pleural effusions (BPE) caused by Mycobacterium tuberculosis infection, heart failure, or infections related to pneumonia. Today, with the rapid advancement of treatment protocols, accurately diagnosing MPE has become increasingly important. Although cytology smears and cell blocks examinations of pleural effusion are the clinical gold standards for diagnosing MPE, the diagnostic accuracy of these tools can be affected by certain limitations, such as low sensitivity, diagnostic variability across different regions and significant inter-observer variability, leading to a certain proportion of misdiagnoses. This study presents a deep learning (DL) framework, namely Interpretable Multi-scale Attention DL with Self-Supervised Learning Feature Encoder (IMA-SSL), to identifyMPE or BPE using 194 Cytological smears whole-slide images (WSIs) and 188 cell blocks WSIs. The use of DL on WSIs of pleural effusion allows for preliminary results to be obtained in a short time, giving patients the opportunity for earlier diagnosis and treatment. The experimental results show that the proposed IMA-SSL consistently obtained superior performance and outperformed five state-of-the-art (SOTA) methods in malignancy prediction on both cell block and cytological smear datasets and also in identification of aggressive endometrial cancer (EC) using a public TCGA dataset. Fisher’s exact test confirmed a highly significant correlation between the outputs of the proposed model and the slide status in the EC and pleural effusion datasets ($\mathrm{p\; <\; 0.001}$), substantiating the model’s predictive reliability. The proposed method has the potential for practical clinical application in the foreseeable future. It can directly detect the presence of malignant tumor cells from cost-effective cell blocks and pleural effusion cytology smears and facilitate personalized cancer treatment decisions.