Benchmarking Computational Pathology Foundation Models For Semantic Segmentation

Foreground segmentation is the critical first step of every computational pathology pipeline, yet existing methods rely on hand-tuned heuristics or supervised models that overfit to narrow stain and scanner distributions, failing silently on specialised stains such as Jones silver or Elastica van Gieson. We propose a coarse-to-fine approach that recasts foreground segmentation as a visual perception task and leverages general-purpose vision-language models (VLMs) as zero-annotation oracles. Our key insight is that tissue-versus-background discrimination is a natural-image recognition problem, not a histopathological one, so VLMs trained on internet-scale corpora generalise where domain-specific models cannot. We introduce Leica-75, a benchmark of 75 renal transplant whole-slide images spanning three stain families. On Leica-75, our method achieves the highest segmentation quality on out-of-distribution stains (Dice 0.858 +/- 0.027 on Jones, 0.853 +/- 0.041 on EVG) with 7x lower cross-stain variance than the best supervised baseline, while remaining competitive on in-distribution H&E. Few-shot prompting with automatically curated exemplars (Auto-context) rescues hard cases on Stress-32 (n=32), a curated stress-test subset (Dice 0.470 to 0.819 for the 2B model). VLM-based annotation review matches human expert consensus (kappa=0.989 for blur detection; mean precision/recall grading accuracy 0.708 vs. human 0.646 for segmentation mask review). The resulting pseudo-labels are used to distil lightweight student models that are as performant as the teacher model while running for a fraction of the cost. Our framework provides a principled, scalable solution to a persistent infrastructure bottleneck in digital pathology.

Foundation models are reshaping computational pathology, yet their capabilities remain shaped by pretraining objectives, data sources, and spatial scales, fragmenting complementary expertise across separate backbones. Here we present ALICE, a unified foundation model trained through multi-stage agglomerative distillation that sequentially distills eight vision-only, vision-language, and slide-level teacher models into dedicated modules of a single backbone. ALICE is pretrained on 24,985,184 tile-level pathology images and 155,604 high-resolution images, and evaluated across 21 task scenarios, 96 downstream tasks, and 48 data sources, spanning region-of-interest tissue analysis, vision-language multimodal evaluation, and whole-slide clinical assessment. In all three evaluation settings, ALICE achieved the best average rank among task-matched pathology foundation models. These results demonstrate that agglomerative distillation can consolidate complementary capabilities from specialized models into a unified backbone for broad computational pathology applications. The model is available at https://github.com/WonderLandxD/ALICE.

Foundation models trained on large pathology image corpora now provide strong, transferable representations for computational pathology. Over the past few years a series of such models has been released, each trained on more slides than the last; on standard classification and segmentation benchmarks, the leading models are now separated by small margins. In clinical use, however, the foundation model is applied to images from hospitals, scanners, and staining protocols outside its training data. Encoders generally embed these acquisition factors alongside biological information, which may introduce downstream errors and hinder safe clinical adoption. A pathology foundation model should therefore be robust to acquisition shift without giving up representation quality, yet robustness is seldom the axis along which models are compared. In this report, we introduce HERO (Histology Encoder for Robust Representation in Oncology), a ViT-G/14 pathology foundation model trained with the DINO and iBOT objectives and refined with high-resolution Gram anchoring on a morphology-balanced corpus of 500 million tiles from approximately 575,000 clinical whole-slide images. Across the evaluated public benchmarks, HERO shows the strongest robustness to center, scanner, and stain variation among the compared state-of-the-art foundation models, performs comparably on tile-level classification, segmentation, and gene-expression prediction, ranks first on average across 39 evaluated slide-level clinical tasks, and, under an equal-weighted framework-level analysis, has the best average rank across the six benchmark frameworks.