The Extravascular Matrix Patterns:
Composition and Role in Tumor Perfusion
Ultrastructurally, extravascular matrix patterns are composed of sheets of lamin between which are sandwhiched melanoma cells. They are therefore not fibrovascular septa.
Uveal melanoma metastatic to the liver, stain for laminin, original magnification X10
Composition of Extravascular Matrix Patterns:
Maniotis AJ, et al. Control of melanoma morphogenesis, endothelial survival, and perfusion by extracellular matrix. Lab Invest 2002;82:1031-1043.
Perfusion in vitro:
Maniotis AJ, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 1999;155:739-752.
Maniotis AJ, et al. Control of melanoma morphogenesis, endothelial survival, and perfusion by extracellular matrix. Lab Invest 2002;82:1031-1043.
Perfusion in animal models:Potgens AJG, et al. Analysis of the tumor vasculature and metastatic behavior of xenografts of human melanoma cell lines transfected with vascular permeability factor. Am J Pathol 1996;148:1203-1217.
Clarijs R, et al. Presence of a fluid-conducting meshwork in xenografted cutaneous and primary human uveal melanoma. Invest Ophthalmol Vis Sci 2002;43:912-918.
Perfusion of these patterns in human uveal melanomas has been demonstrated by confocal laser scanning angiography after intravenous injection of indocyanine green. The patterns become visible 15 second after injection of ICG into the antecubital vein. Fibrinogen, a surrogate maker for plasma, co-localizes to extravascular matrix patterns in tissue sections of human uveal melanoma (ultrastructural studies do not detect fibrin in the extravascular matrix patterns - fibrin has a characteristic ultrastructural appearance). The absence of thrombosis in extravascular matrix patterns may be explained by elaboration of Tissue Factor Pathway Inhibitors 1 and 2 by the aggressive uveal melanoma cells that generate these patterns.
Perfusion in tissue sections of human uveal melanoma:
Chen X, et al. Uveal melanoma cell staining for CD34 and assessment of tumor vascularity. Invest Ophthalmol Vis Sci 2002;43:2533-2539.
Chen X, et al. Three-dimensional reconstruction of extravascular matrix patterns and blood vessels in human uveal melanoma tissue: techniques and preliminary findings. Invest Ophthalmol Vis Sci 2003 (in press).
Perfusion in patients by confocal laser scanning angiography after injection of indocyanine green:
Mueller AJ, et al. Imaging the microvasculature of choroidal melanomas with confocal indocyanine green scanning laser ophthalmoscopy. Arch Ophthalmol 1998;116:31-39.