Clinical Pathological Characteristics And Pathogenetic Factors Of Orbital Venous Malformation

Objective: To review the clinical manifestations of orbital venous malformations,and analyze the clinical features of rare cases;We summarized the structural and molecular pathological characteristics of orbital venous malformations in the aspects of vascular diameter,thickness,expression level of specific molecular markers and matrix protein in endothelial cells,based on the routine pathology analysis.We also detected the expression of matrix remodeling factor,angiogenesis related factors and inflammatory related factors,and analyzed their relationship with orbital venous malformations.Methods: Part One: 370 cases of orbital venous malformations admitted in Shanghai Ninth People's Hospital,Shanghai Jiaotong University School of Medicine from 2006 to 2016 were retrospectively reviewed.We analyzed their clinical data,and summarized the clinical features of orbital venous malformations;We used HE staining and immunohistochemical staining to observe and measure distensible venous malformation(20 cases),indistensible venous malformation(20 cases)and normal blood vessel(10 cases)tissue structures;We detected and analyzed the expression of endothelial cell specific marker CD31,lymphatic endothelial specific marker D2-40 and vascular smooth muscle cell marker ?-SMA.Part Two: We detected the expression level of matrix proteins(fibronectin and desmin),vascular endothelial growth factors(VEGF-A,VEGF-C,VEGF-D)and inflammation related factors(CD4,CD41,CD45,CD8,and CD68)in distensible venous malformation(10 cases)and indistensible venous malformation(10 cases)and normal blood vessels(5 cases)through immunohistochemical staining.Results: Part One:(1)Orbital venous malformations generally occur at birth,and develop with growth.Superficial lesions usually affect the appearance,while deep lesions often cause exophthalmos,eye movement limitation,and vision impairment;Some rare cases have special manifestations,like bone defect and bone enlargement.(2)The vascular diameter of distensible venous malformation was larger than that of the indistensible type,and the ratio of vascular diameter to wall thickness of the two types were much larger than that of the normal vein.(3)The expression of ?-SMA in venous malformation was significantly lower than that in normal veins;the expression level of CD31 was similar to normal veins,and the D2-40 expression level of distensible type was lower than that of indistensible type.Part Two:(1)The expression of fibronectin and desmin in orbital venous malformation was significantly lower than that in normal vein.(2)The expression level of VEGF-A in venous malformation was higher than normal vein wall,while expression level was close in distensible and indistensible types;The expression of VEGF-C in indistensible venous malformation is higher than that in distensible venous malformation and normal blood vessels;the expression level of VEGF-D in venous malformation is similar to that in normal vessels.(3)The expression levels of CD4,CD8,CD41,CD45 and CD68 in venous malformations were higher than those in normal vessels.Conclusion:(1)Orbital venous malformation has various clinical presentations.Some rare cases can affect bony structure,which may cause misdiagnosis.(2)The development of endothelial cells and the muscular layer in orbital venous malformations are unbalanced.Vascular wall weakness is the main pathologic structural foundation.(3)The abnormal expressions of vascular endothelial growth factor,matrix protein and inflammatory factors in orbital venous malformation are related to the pathogenesis of orbital venous malformations.