Health-System-Wide Mapping of Demographic Information in Routine Clinical Histopathology
Abstract: The extent to which demographic-associated information is detectable across organs and disease states in routine clinical histopathology remains unclear. Here, we analyzed 1.3 million hematoxylin and eosin whole-slide images from 257,322 patients across 25 organs, using pathology foundation-model representations and multiple-instance learning to systematically map information associated with sex, age group, and self-reported race. Across 69 organ-demographic combinations, demographic attributes were broadly recoverable, with pan-organ mean AUROCs of 0.828 for sex, 0.733 for age group, and 0.662 for self-reported race, and substantial variation across organs. Demographic-class balancing produced relatively small changes in performance, while evaluation within diagnosis-text clusters showed modest attenuation. Under training with diagnosis-based grouping, demographic-associated signals remained detectable across multiple organs, including sex in gastric tissue (AUROC 0.865), age group in breast (0.816), and self-reported race in skin (0.728). Literature-guided analysis of these settings generated candidate histomorphological and contextual explanations for further investigation. Together, these findings provide a systematic map of demographic-associated information in routine histopathology, informing investigations of its sources, assessments of potential shortcut learning, and the development of more interpretable computational pathology models.