Pretraining on large-scale, in-domain datasets grants histopathology foundation models (FM) the ability to learn task-agnostic data representations, enhancing transfer learning on downstream tasks. In computational pathology, automated whole slide image analysis requires multiple instance learning (MIL) frameworks due to the gigapixel scale of the slides. The diversity among histopathology FMs has highlighted the need to design real-world challenges for evaluating their effectiveness. To bridge this gap, our work presents a novel benchmark for evaluating histopathology FMs as patch-level feature extractors within a MIL classification framework. For that purpose, we leverage the AI4SkIN dataset, a multi-center cohort encompassing slides with challenging cutaneous spindle cell neoplasm subtypes. We also define the Foundation Model - Silhouette Index (FM-SI), a novel metric to measure model consistency against distribution shifts. Our experimentation shows that extracting less biased features enhances classification performance, especially in similarity-based MIL classifiers.

This study evaluates the generalisation capabilities of state-of-the-art histopathology foundation models on out-of-distribution (OOD) multi-stain autoimmune Immunohistochemistry (IHC) datasets. We compare 13 feature extractor models, including ImageNet-pretrained networks, and histopathology foundation models trained on both public and proprietary data, on Rheumatoid Arthritis (RA) subtyping and Sjogren's Disease (SD) diagnostic tasks. Using a simple Attention-Based Multiple Instance Learning classifier, we assess the transferability of learned representations from cancer H&E images to autoimmune IHC images. Contrary to expectations, histopathology-pretrained models did not significantly outperform ImageNet-pretrained models. Furthermore, there was evidence of both autoimmune feature misinterpretation and biased feature importance. Our findings highlight the challenges in transferring knowledge from cancer to autoimmune histopathology and emphasise the need for careful evaluation of AI models across diverse histopathological tasks.

Bevacizumab is a widely studied targeted therapeutic drug used in conjunction with standard chemotherapy for the treatment of recurrent ovarian cancer. While its administration has shown to increase the progression-free survival (PFS) in patients with advanced stage ovarian cancer, the lack of identifiable biomarkers for predicting patient response has been a major roadblock in its effective adoption towards personalized medicine. In this work, we leverage the latest histopathology foundation models trained on large-scale whole slide image (WSI) datasets to extract ovarian tumor tissue features for predicting bevacizumab response from WSIs. Our extensive experiments across a combination of different histopathology foundation models and multiple instance learning (MIL) strategies demonstrate capability of these large models in predicting bevacizumab response in ovarian cancer patients with the best models achieving an AUC score of 0.86 and an accuracy score of 72.5%. Furthermore, our survival models are able to stratify high- and low-risk cases with statistical significance (p < 0.05) even among the patients with the aggressive subtype of high-grade serous ovarian carcinoma. This work highlights the utility of histopathology foundation models for the task of ovarian bevacizumab response prediction from WSIs. The high-attention regions of the WSIs highlighted by these models not only aid the model explainability but also serve as promising imaging biomarkers for treatment prognosis.