Clinical implications and mechanism of histopathological growth pattern in colorectal cancer liver metastases

Liver is the most common site of metastases of colorectal cancer, and liver metastases present with distinct histopathological growth patterns (HGPs), including desmoplastic, pushing and replacement HGPs and two rare HGPs. HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics. Many studies have revealed the association of HGPs with carcinogenesis, angiogenesis, and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications. These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making, and a target of imaging observation for patient screening. Of note, it is crucial to determine the underlying mechanism shaping HGP, for instance, immune infiltration and extracellular matrix remodeling in desmoplastic HGP, and aggressive characteristics and special vascularization in replacement HGP (rHGP). We highlight the importance of aggressive features, vascularization, host immune and organ structure in formation of HGP, hence propose a novel "advance under camouflage" hypothesis to explain the formation of rHGP.