PathOrchestra: A Comprehensive Foundation Model for Computational Pathology with Over 100 Diverse Clinical-Grade Tasks

The complexity and variability inherent in high-resolution pathological images present significant challenges in computational pathology. While pathology foundation models leveraging AI have catalyzed transformative advancements, their development demands large-scale datasets, considerable storage capacity, and substantial computational resources. Furthermore, ensuring their clinical applicability and generalizability requires rigorous validation across a broad spectrum of clinical tasks. Here, we present PathOrchestra, a versatile pathology foundation model trained via self-supervised learning on a dataset comprising 300K pathological slides from 20 tissue and organ types across multiple centers. The model was rigorously evaluated on 112 clinical tasks using a combination of 61 private and 51 public datasets. These tasks encompass digital slide preprocessing, pan-cancer classification, lesion identification, multi-cancer subtype classification, biomarker assessment, gene expression prediction, and the generation of structured reports. PathOrchestra demonstrated exceptional performance across 27,755 WSIs and 9,415,729 ROIs, achieving over 0.950 accuracy in 47 tasks, including pan-cancer classification across various organs, lymphoma subtype diagnosis, and bladder cancer screening. Notably, it is the first model to generate structured reports for high-incidence colorectal cancer and diagnostically complex lymphoma-areas that are infrequently addressed by foundational models but hold immense clinical potential. Overall, PathOrchestra exemplifies the feasibility and efficacy of a large-scale, self-supervised pathology foundation model, validated across a broad range of clinical-grade tasks. Its high accuracy and reduced reliance on extensive data annotation underline its potential for clinical integration, offering a pathway toward more efficient and high-quality medical services.

Task-oriented Embedding Counts: Heuristic Clustering-driven Feature Fine-tuning for Whole Slide Image Classification

In the field of whole slide image (WSI) classification, multiple instance learning (MIL) serves as a promising approach, commonly decoupled into feature extraction and aggregation. In this paradigm, our observation reveals that discriminative embeddings are crucial for aggregation to the final prediction. Among all feature updating strategies, task-oriented ones can capture characteristics specifically for certain tasks. However, they can be prone to overfitting and contaminated by samples assigned with noisy labels. To address this issue, we propose a heuristic clustering-driven feature fine-tuning method (HC-FT) to enhance the performance of multiple instance learning by providing purified positive and hard negative samples. Our method first employs a well-trained MIL model to evaluate the confidence of patches. Then, patches with high confidence are marked as positive samples, while the remaining patches are used to identify crucial negative samples. After two rounds of heuristic clustering and selection, purified positive and hard negative samples are obtained to facilitate feature fine-tuning. The proposed method is evaluated on both CAMELYON16 and BRACS datasets, achieving an AUC of 97.13% and 85.85%, respectively, consistently outperforming all compared methods.