FedHisto-PAST: Parameter-Efficient Stain-Aware Federated Learning for Cross-Site Lung Histopathology Classification

Robust whole-slide image (WSI) analysis under strict data-governance remains challenging due to substantial cross-institutional stain heterogeneity. Domain generalization (DG) mitigates these shifts but typically requires centralized data, conflicting with privacy regulations. Federated learning (FedL) provides a decentralized alternative; however, existing FedL and federated DG (FedDG) approaches rely almost exclusively on low-order statistics, assuming Gaussian-like stain distributions. In contrast, real-world staining processes often produce asymmetric, heavy-tailed color distributions due to biochemical diffusion and scanner nonlinearity. Consequently, current methods fail to model the higher-order, non-Gaussian characteristics dominating real-world stain variability. To address this, we propose FedStain, a stain-aware FedDG framework explicitly incorporating higher-order stain moments--skewness and kurtosis--as compact statistical descriptors exchanged during federated optimization. These descriptors require no pixel-level data transmission, preserving strict privacy and communication efficiency, while enabling the global model to capture stain variability missed by low-order statistics. FedStain also employs a contrastive, cross-site parameter aggregation strategy to promote stain-invariant representations without relaxing data constraints. Extensive experiments on Camelyon17 and our new MvMidog-Fed benchmark show FedStain yields consistent improvements, outperforming state-of-the-art FedL, DG, and FedDG baselines by up to +3.9% absolute accuracy. To our knowledge, FedStain is the first FedDG approach to explicitly model higher-order stain statistics, enabling robust cross-institutional deployment in computational pathology.

Federated learning (FL) offers a promising framework for collaborative digital pathology by enabling model training across institutions. However, real-world deployments face heterogeneity arising from diverse multiple instance learning (MIL) architectures and heterogeneous feature extractors across institutions. We propose FedHD, a novel FL framework that performs local Gaussian-mixture feature alignment tailored for WSI analysis. Instead of exchanging model parameters, each client independently distills semantically rich synthetic feature representations aligned with the distribution of real WSIs. To preserve diagnostic diversity, FedHD adopts a one-to-one distillation strategy, generating a synthetic counterpart for each real slide to avoid over-compression. During federation, a curriculum-based integration strategy progressively incorporates cross-site synthetic features into local training once performance plateaus. Furthermore, an optional interpretation module reconstructs pseudo-patches from synthetic embeddings, enhancing transparency. FedHD is architecture-agnostic, privacy-preserving, and supports personalized yet collaborative training across diverse institutions. Experiments on TCGA-IDH, CAMELYON16, and CAMELYON17 show that FedHD consistently outperforms state-of-the-art federated and distillation baselines.

Breast histopathology analysis increasingly relies on distributed learning because direct data pooling across institutions is often restricted by privacy, governance, and communication constraints. This study compares server-based Federated Averaging (FedAvg), fully decentralized gossip learning, and Hybrid Gossip-FedAvg for invasive ductal carcinoma (IDC) patch classification. Experiments used 277,524 color image patches with patient-disjoint training, validation, and test partitions and a workload-balanced, Dirichlet-guided allocation across six nodes. Ring, random degree-3, and fully connected gossip topologies were evaluated together with sensitivity analyses for statistical heterogeneity, mixing coefficient, learning rate, model drift, prediction disagreement, calibration, clinically motivated operating points, communication payload, and patient-level IDC burden, together with auxiliary backbone robustness analyses. In the principal alpha=0.3 experiment, Hybrid Gossip-FedAvg achieved a test area under the receiver operating characteristic curve (ROC-AUC) of 0.8811, closely followed by FedAvg at 0.8801 and fully connected gossip at 0.8751. Across three independent patient-level repetitions, FedAvg and Hybrid Gossip-FedAvg obtained the same mean ROC-AUC of 0.9082, with standard deviations of 0.0037 and 0.0043, respectively. Hybrid achieved the highest mean area under the precision-recall curve of 0.8240, whereas FedAvg produced the lowest mean Brier score of 0.1335. Denser gossip graphs improved discrimination but increased theoretical model payload, while ring gossip remained sensitive to learning rate and mixing strength. Overall, FedAvg provided the most consistently reliable server-based baseline, topology-aware gossip offered a viable decentralized alternative, and Hybrid Gossip-FedAvg provided a balanced compromise between peer-to-peer diffusion and periodic global coordination.