Computational Pathology for Prediction of Isocitrate Dehydrogenase Gene Mutation from Whole Slide Images in Adult Patients with Diffuse Glioma

Isocitrate dehydrogenase gene (IDH) mutation is one of the most important molecular markers of glioma. Accurate detection of IDH status is a crucial step for integrated diagnosis of adult-type diffuse gliomas. A clustering-based hybrid of a convolutional neural network and a vision transformer deep learning model was developed to detect IDH mutation status from annotation-free hematoxylin and eosin–stained whole slide pathologic images of 2275 adult patients with diffuse gliomas. For comparison, we also assessed a pure convolutional neural network, a pure vision transformer, and a classic multiple-instance learning model. The hybrid model achieved an area under the receiver operating characteristic curve of 0.973 in the validation set and 0.953 in the external test set, outperforming the other models. We further assessed the hybrid model's ability in IDH detection between difficult subgroups with different IDH status but shared histologic features, achieving areas under the receiver operating characteristic curve ranging from 0.850 to 0.985 in validation and test sets. Our data suggest that the proposed hybrid model has a potential to be used as a computational pathology tool for preliminary rapid detection of IDH mutation from whole slide images in adult patients with diffuse gliomas.