| Objective: To evaluate the intratumoral microhemorrhage of vestibular schwannomas(VSs)by preoperative MRI Susceptibility Weighted Imaging(SWI)imaging and postoperative histology,and to explore the related factors to VSs intratumoral microhemorrhage and microvascular mechanism.Methods: 61 patients with VSs treated by microsurgery in our hospital between June 2018 to October 2019 were selected.MRI-SWI was used to evaluate the intratumoral microhemorrhage in VSs patients before operation.The ratio of the axial image microhemorrhage area of the largest slice of the tumor cerebellopontine angle region to the solid component area of this slice was recorded as microhemorrhage area ratio.According to the microhemorrhage area ratio,the hemorrhage was divided into three groups: mild group(< 25%),moderate group(25% ~ 50%)and severe group(> 50%);to evaluate the correlation between tumor size,cystic and solid and microhemorrhage.Tumor specimens were taken during the operation,and routine HE staining was used to confirm the histopathological diagnosis.Perls stain was used to evaluate the histology of microhemorrhage in the tumor.According to the staining range,microhemorrhage was divided into "mild" scattered staining,"moderate" extensive staining and "severe" diffuse staining,and analyze the consistency between SWI classification and histological classification of microhemorrhage.to analyze the correlation between histomorphology(Antoni A,Antoni B,mixed type)and microhemorrhage;Immunohistochemical staining of CD34 labeled microvessels was used to analyze the correlation between tumor microvessel density(MVD)and microhemorrhage.The expressions of MMP-2,MMP-9,TIMP1,ZO-1 and Occludin were detected by immunohistochemical method.The concentrations of the above-mentioned indexes were detected by ELISA in 10 tumors randomly selected from each group,and the correlation between the above-mentioned indexes and microhemorrhage was analyzed.Results:(1)61 patients(100%)with VSs showed microhemorrhage on SWI,with SWI classification of 24 cases in mild group,14 cases in moderate group and 23 cases in severe group.Perls stain confirmed hemosiderin deposition in all cases after operation,including 27 cases of "mild",13 cases of "moderate" and 21 cases of "severe".Compared SWI grading with histological grading,a total of 56 cases(91.8%)were consistent,with good consistency(Kappa=0.873,p < 0.001)and paired chi-square test P=0.82,with no significant difference.The results of the two methods were the same.(2)The tumor volume of mild-moderate-severe microhemorrhage group was 12.87±11.21cm3,11.58±11.51cm3 and 9.60±5.21cm3 respectively,and there was no significant difference by analysis of variance(P > 0.05).(3)There were 11 cases(45.8%)of cystic VSs and 13 cases(51.2%)of solid VSs in SWI mild grade group;There were 11 cases of cystic VSs(78.6%)and 3 cases of solid VSs(21.4%)in moderate microhemorrhage group.There were 18 cases of cystic VSs(78.3%)and 5 cases of solid VSs(21.7%)in the severe microhemorrhage group.There was significant difference in the proportion of cystic VSs between the three groups(P < 0.05).The comparative analysis between the two groups showed that there was significant difference between the mild group and the moderate group,the mild group and the severe group(P < 0.05),but there was no significant difference between the moderate group and the severe group(P > 0.05).(4)There were 15 cases(55.6%)of Antoni A,1 case(3.7%)of Antoni B and 11 cases(40.7%)of mixed type in Perls stain group;There were 2 cases(15.4%)of Antoni A,1 case(7.7%)of Antoni B and 10 cases(76.9%)of mixed type in moderate group;In the severe group,2 cases(9.5%)were Antoni A,4 cases(19.0%)were Antoni B and 15 cases(71.4%)were mixed.There were significant differences in tumor histomorphology among mild group,moderate group and severe group(P < 0.05).The comparative analysis between the two groups showed that the difference between the mild group and the severe group was statistically significant(P < 0.05),while the difference between the mild group and the moderate group and between the moderate group and the severe group was not statistically significant(P > 0.05).(5)The MVD of mild,moderate and severe groups were 38.17±5.26,58.62±8.01 and 90.55±15.13 respectively by Perls stain.The MVD of the three groups showed an increasing trend in turn,and the difference was statistically significant by one-way ANOVA(P < 0.05).(6)Immunohistochemical staining of MMP-2,MMP-9,TIMP-1,ZO-1 and Occlcdin was found in all 61 cases of VSs tumors.The average optical density of MMP-2 and MMP-9 increased in mild-moderate-severe groups(P < 0.01);TIMP-1,ZO-1 and Occlcdin showed a decreasing trend(P < 0.01);The difference of MMP-9 and ZO-1 between two groups was statistically significant;The difference of MMP-2,TIMP-1 and Occlcdin between mild group and severe group,moderate group and severe group was statistically significant(P < 0.01).There was no statistical difference between mild group and moderate group(P > 0.05).(7)The expressions of MMP-2,MMP-9,TIMP-1,ZO-1 and Occlcdin were found in all 30 VSs detected by ELISA.The concentrations of MMP-2,MMP-9 in the homogenate of mild,moderate and severe tumor tissues showed an increasing trend(P < 0.01),while the concentrations of TIMP-1,ZO-1 and Occlcdin showed a decreasing trend(P < 0.01).The comparison of each index between the two groups was statistically significant(P < 0.05).Linear regression analysis showed that the concentration of MMP-2 and MMP-9 was negatively correlated with the concentration of ZO-1 and Occludin protein,while the concentration of TIMP was positively correlated with the concentration of ZO-1 and Occludin protein.Conclusion:(1)Imaging SWI grading of VSs intratumoral microhemorrhage is in good agreement with histological Perls stain grading.Preoperative SWI is a reliable method to predict intratumoral microhemorrhage in VSs patients(sensitivity 100%,specificity 100%).(2)The grade of microhemorrhage in VSs has nothing to do with tumor volume.(3)The proportion of cystic degeneration in VSs with high grade of intratumoral microhemorrhage is higher,which suggests that intratumoral microhemorrhage may be involved in the occurrence of cystic degeneration in VSs.(4)Antoni A was common in patients with low grade of VSs,and Antoni B and mixed type were common in patients with high grade of VSs.It is suggested that histological typing of VSs is related to intratumoral microhemorrhage.(5)The higher the grade of VSs microhemorrhage,the more the tumor microvessel count,suggesting that the increase of microvessel density(MVD)is related to microhemorrhage.(6)The expression activity of MMP-2 and MMP-9 in the three groups of mild,moderate and severe microhemorrhage showed an increasing trend(P < 0.01),while the expression activity of TIMP-1,ZO-1 and Occlcdin showed a decreasing trend(P < 0.01);The expression levels of MMP-2 and MMP-9 were negatively correlated with the concentration of ZO-1 and Occludin,suggesting that the high expression of matrix metalloproteinases can degrade ZO-1 and Occludin,which are important components of tight junction.Vascular tight junction-basement membrane dysfunction may be one of the mechanisms of microhemorrhage in VSs. |
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