Histopathological growth patterns represent a dynamic biological and clinically-relevant terminus of the metastatic cascade

The metastatic cascade describes the series of steps by which cancer cells travel from the tumor of origin to a distant site of metastasis. Successful colonization and formation of macrometastases are generally regarded as the terminus of the metastatic cascade. However, a growing body of literature points to the importance of inter- and intra-tumoral heterogeneity during the growth of established metastases, which manifests as distinct histopathological growth patterns (HGPs). HGPs refer to the dynamic interface between cancer cells, stromal cells and parenchymal cells within the metastasis-bearing organ. In several metastatic niches, such as the liver and brain, unique HGPs have been described that reveal aspects of intrinsic disease biology and have important implications for patient survival and therapy response. With emerging technologies, recent studies have revealed spatial insights pertaining to cancer cell—tumor microenvironment interactions at distinct metastatic sites. Herein, we describe the clinical and biological relevance of the dynamic interplay between cancer cells and the native liver or brain cells in the context of metastases from adult solid tumors. When applicable, we draw comparisons between metastatic sites and identify common themes by which HGP and components of the tumor microenvironment can be exploited for therapeutic intervention.