Abstract:Recent deep learning frameworks in histopathology, particularly multiple instance learning (MIL) combined with pathology foundational models (PFMs), have shown strong performance. However, PFMs exhibit limitations on certain cancer or specimen types due to domain shifts - these cancer types were rarely used for pretraining or specimens contain tissue-based artifacts rarely seen within the pretraining population. Such is the case for transurethral resection of bladder tumor (TURBT), which are essential for diagnosing muscle-invasive bladder cancer (MIBC), but contain fragmented tissue chips and electrocautery artifacts and were not widely used in publicly available PFMs. To address this, we propose a simple yet effective domain-adaptive self-supervised adaptor (DA-SSL) that realigns pretrained PFM features to the TURBT domain without fine-tuning the foundational model itself. We pilot this framework for predicting treatment response in TURBT, where histomorphological features are currently underutilized and identifying patients who will benefit from neoadjuvant chemotherapy (NAC) is challenging. In our multi-center study, DA-SSL achieved an AUC of 0.77+/-0.04 in five-fold cross-validation and an external test accuracy of 0.84, sensitivity of 0.71, and specificity of 0.91 using majority voting. Our results demonstrate that lightweight domain adaptation with self-supervision can effectively enhance PFM-based MIL pipelines for clinically challenging histopathology tasks. Code is Available at https://github.com/zhanghaoyue/DA_SSL_TURBT.




Abstract:Cancer subtyping is one of the most challenging tasks in digital pathology, where Multiple Instance Learning (MIL) by processing gigapixel whole slide images (WSIs) has been in the spotlight of recent research. However, MIL approaches do not take advantage of inter- and intra-magnification information contained in WSIs. In this work, we present GRASP, a novel graph-structured multi-magnification framework for processing WSIs in digital pathology. Our approach is designed to dynamically emulate the pathologist's behavior in handling WSIs and benefits from the hierarchical structure of WSIs. GRASP, which introduces a convergence-based node aggregation instead of traditional pooling mechanisms, outperforms state-of-the-art methods over two distinct cancer datasets by a margin of up to 10% balanced accuracy, while being 7 times smaller than the closest-performing state-of-the-art model in terms of the number of parameters. Our results show that GRASP is dynamic in finding and consulting with different magnifications for subtyping cancers and is reliable and stable across different hyperparameters. The model's behavior has been evaluated by two expert pathologists confirming the interpretability of the model's dynamic. We also provide a theoretical foundation, along with empirical evidence, for our work, explaining how GRASP interacts with different magnifications and nodes in the graph to make predictions. We believe that the strong characteristics yet simple structure of GRASP will encourage the development of interpretable, structure-based designs for WSI representation in digital pathology. Furthermore, we publish two large graph datasets of rare Ovarian and Bladder cancers to contribute to the field.