Histopathological images contain abundant phenotypic information and pathological patterns, which are the gold standards for disease diagnosis and essential for the prediction of patient prognosis and treatment outcome. In recent years, computer-automated analysis techniques for histopathological images have been urgently required in clinical practice, and deep learning methods represented by convolutional neural networks have gradually become the mainstream in the field of digital pathology. However, obtaining large numbers of fine-grained annotated data in this field is a very expensive and difficult task, which hinders the further development of traditional supervised algorithms based on large numbers of annotated data. More recent studies have started to liberate from the traditional supervised paradigm, and the most representative ones are the studies on weakly supervised learning paradigm based on weak annotation, semi-supervised learning paradigm based on limited annotation, and self-supervised learning paradigm based on pathological image representation learning. These new methods have led a new wave of automatic pathological image diagnosis and analysis targeted at annotation efficiency. With a survey of over 130 papers, we present a comprehensive and systematic review of the latest studies on weakly supervised learning, semi-supervised learning, and self-supervised learning in the field of computational pathology from both technical and methodological perspectives. Finally, we present the key challenges and future trends for these techniques.

Weakly supervised whole slide image classification is usually formulated as a multiple instance learning (MIL) problem, where each slide is treated as a bag, and the patches cut out of it are treated as instances. Existing methods either train an instance classifier through pseudo-labeling or aggregate instance features into a bag feature through attention mechanisms and then train a bag classifier, where the attention scores can be used for instance-level classification. However, the pseudo instance labels constructed by the former usually contain a lot of noise, and the attention scores constructed by the latter are not accurate enough, both of which affect their performance. In this paper, we propose an instance-level MIL framework based on contrastive learning and prototype learning to effectively accomplish both instance classification and bag classification tasks. To this end, we propose an instance-level weakly supervised contrastive learning algorithm for the first time under the MIL setting to effectively learn instance feature representation. We also propose an accurate pseudo label generation method through prototype learning. We then develop a joint training strategy for weakly supervised contrastive learning, prototype learning, and instance classifier training. Extensive experiments and visualizations on four datasets demonstrate the powerful performance of our method. Codes will be available.