CellPath-Bench: A Multidimensional Benchmark for Whole-Slide Cellular Representations in Pathology Foundation Models

Abstract

Pathology foundation models (PFMs) are increasingly used as general-purpose backbones, yet existing benchmarks cannot systematically diagnose their whole-slide cellular representation capabilities, including the decodability of cell-type information and the transferability of such information across tissue sections, datasets, and anatomical organs. We introduce CellPath-Bench, a cellular-resolution benchmark that evaluates frozen PFMs themselves. Following quality control of 52 candidate Xenium datasets, we construct a panel of 25 spatially aligned H\&E--Xenium tissue sections spanning 11 organs and 7,079,283 cells, harmonized into fine- and coarse-grained taxonomies. CellPath-Bench samples frozen WSI feature maps at registered nuclear coordinates and evaluates them using standardized multiclass linear probes. Cell Representation Advantage (CRA) measures the within-section advantage of nucleus-anchored representations over patch-level mean pooling, while Cell Representation Transferability (CRT) characterizes the generalization of cell-type decodability across tissue sections, datasets, and organs. We benchmark 30 pathology-specific and general-purpose foundation models through 304,920 runs across spatial readouts, magnifications, taxonomic granularities, and evaluation protocols. The results reveal substantial model-dependent differences in cell-type decodability and its cross-domain generalization, yielding distinct multidimensional capability profiles. CellPath-Bench provides a standardized framework for auditing cellular information in frozen PFM representations.