Hematogenous metastases of the human brain--characteristics of peritumoral brain changes: a review

The brain is an important site of hematogenous metastases from malignant tumors in other organs. The effects on the brain is a combination of tissue destruction induced by invading tumor cells and reactive alterations occurring around the metastases. This review focuses on neuropathological changes around hematogenous metastases of the human brain. The peritumoral brain parenchyma shows structural and functional changes of the intracerebral microvessels and edema. The endothelial cells of peritumoral microvessels express glucose transporter protein (GLUT 1) in the same way as the normal brain. Reduction in immunostaining to GLUT 1 may occur in the microvessels located within the metastases. This would indicate abnormalities of the blood-brain barrier in tumor vessels but normal barrier function in the peritumoral region. Reactive astrocytes and activated microglial cells are both involved in the process of peritumoral gliosis. Activated glial cells produce numerous biological active compounds including endothelin-1 which after release from such cells can influence the structure and function of the peritumoral brain tissue. Lesions of oligodendrocytes and edema may be implicated in myelin degeneration. Finally, metastases will induce axonal and neuronal injuries as indicated by a recent study on expression of beta-amyloid precursor protein (beta APP) in reactive axonal swellings.