In non-medical domains, foundation models (FMs) have revolutionized computer vision and language processing through large-scale self-supervised and multimodal learning. Consequently, their rapid adoption in computational pathology was expected to deliver comparable breakthroughs in cancer diagnosis, prognostication, and multimodal retrieval. However, recent systematic evaluations reveal fundamental weaknesses: low diagnostic accuracy, poor robustness, geometric instability, heavy computational demands, and concerning safety vulnerabilities. This short paper examines these shortcomings and argues that they stem from deeper conceptual mismatches between the assumptions underlying generic foundation modeling in mainstream AI and the intrinsic complexity of human tissue. Seven interrelated causes are identified: biological complexity, ineffective self-supervision, overgeneralization, excessive architectural complexity, lack of domain-specific innovation, insufficient data, and a fundamental design flaw related to tissue patch size. These findings suggest that current pathology foundation models remain conceptually misaligned with the nature of tissue morphology and call for a fundamental rethinking of the paradigm itself.
Hamid R. Tizhoosh (Mon,) studied this question.