MIST: Multi-instance selective transformer for histopathological subtype prediction

Accurate histopathological subtype prediction is clinically significant for cancer diagnosis and tumor microenvironment analysis. However, achieving accurate histopathological subtype prediction is a challenging task due to (1) instance-level discrimination of histopathological images, (2) low inter-class and large intra-class variances among histopathological images in their shape and chromatin texture, and (3) heterogeneous feature distribution over different images. In this paper, we formulate subtype prediction as fine-grained representation learning and propose a novel multi-instance selective transformer (MIST) framework, effectively achieving accurate histopathological subtype prediction. The proposed MIST designs an effective selective self-attention mechanism with multi-instance learning (MIL) and vision transformer (ViT) to adaptive identify informative instances for fine-grained representation. Innovatively, the MIST entrusts each instance with different contributions to the bag representation based on its interactions with instances and bags. Specifically, a SiT module with selective multi-head self-attention (S-MSA) is well-designed to identify the representative instances by modeling the instance-to-instance interactions. On the contrary, a MIFD module with the information bottleneck is proposed to learn the discriminative fine-grained representation for histopathological images by modeling instance-to-bag interactions with the selected instances. Substantial experiments on five clinical benchmarks demonstrate that the MIST achieves accurate histopathological subtype prediction and obtains state-of-the-art performance with an accuracy of 0.936. The MIST shows great potential to handle fine-grained medical image analysis, such as histopathological subtype prediction in clinical applications.