It is clinically crucial and potentially very beneficial to be able to analyze and model directly the spatial distributions of cells in histopathology whole slide images (WSI). However, most existing WSI datasets lack cell-level annotations, owing to the extremely high cost over giga-pixel images. Thus, it remains an open question whether deep learning models can directly and effectively analyze WSIs from the semantic aspect of cell distributions. In this work, we construct a large-scale WSI dataset with more than 5 billion cell-level annotations, termed WSI-Cell5B, and a novel hierarchical Cell Cloud Transformer (CCFormer) to tackle these challenges. WSI-Cell5B is based on 6,998 WSIs of 11 cancers from The Cancer Genome Atlas Program, and all WSIs are annotated per cell by coordinates and types. To the best of our knowledge, WSI-Cell5B is the first WSI-level large-scale dataset integrating cell-level annotations. On the other hand, CCFormer formulates the collection of cells in each WSI as a cell cloud and models cell spatial distribution. Specifically, Neighboring Information Embedding (NIE) is proposed to characterize the distribution of cells within the neighborhood of each cell, and a novel Hierarchical Spatial Perception (HSP) module is proposed to learn the spatial relationship among cells in a bottom-up manner. The clinical analysis indicates that WSI-Cell5B can be used to design clinical evaluation metrics based on counting cells that effectively assess the survival risk of patients. Extensive experiments on survival prediction and cancer staging show that learning from cell spatial distribution alone can already achieve state-of-the-art (SOTA) performance, i.e., CCFormer strongly outperforms other competing methods.
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