The pathological landscape of tumor evolution: a paradigm shift from morphology to functional networks

Tumor pathology is undergoing a profound transformation, shifting from pure morphological description toward multidimensional functional network analysis. This Mini Review focuses on the tumor microenvironment (TME) as a central concept driving tumor initiation, progression, and therapeutic resistance. We first outline the limitations of traditional pathological classification and elaborate on how the dynamic co-evolution of cellular components (such as cancer-associated fibroblasts (CAFs) and immune cells) along with the extracellular matrix (ECM) constitutes a functional unit. Key controversies are discussed, including the translational hurdles of TME-directed therapies and the challenge of spatiotemporally assessing tumor heterogeneity. We further identify critical research gaps, particularly the mechanistic understanding of the tumor-host interface across scales. Finally, we envision that the integration of artificial intelligence–driven spatial pathology, single-cell multi-omics, and in vivo imaging will usher in a new era of “functional pathology,” merging morphology, molecular profiling, and dynamic insights.