Spectrum of concomitant brain vascular lesions in pediatric diffuse gliomas

Abstract

Cerebrovascular disease represents a threatening factor for brain cancer survivors. However, a comprehensive evaluation of small vessel disease related to gliomas has not yet been performed. This study aims to characterize concomitant vascular lesions in pediatric diffuse gliomas and identify their association with the molecular subgroup of tumors. We performed a retrospective pathological study of biopsy samples of 77 pediatric patients with diffuse gliomas, treated in Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. Eight molecular subgroups were identified by immunohistochemical and cytogenetic studies (H3K27mut, ALT, IDH1mut, BRAFmut-PXA, FGFR1, BRAFmut/FGFR2, RTK, MYB). In each group microvessel density/area (MVD/MVA), tumor vessels co-option and signs of small vessels disease (SVD) were determined. The levels of microvascularization significantly differed between the molecular subgroups of diffuse gliomas, indicating the presence of intrinsic pro-angiogenic activity there. The highest values of MVD/MVA, as well as rate of hemorrhagic necrosis, were found in the BRAFmut/FGFR2, RTK groups. SVD was common in the adjacent tissues of gliomas and occurred in 32.5 % of cases. High grade SVD was associated with the BRAFmut/FGFR2 and IDH1mut subgroups. BRAFmut/FGFR2 tumors were more aggressive and caused cortical microinfarctions in 84,6 % and leukoaraiosis in 87.5 % of cases. IDH1mut tumors were mainly linked with cortical microinfarctions (60 % of cases). The results of the study suggest that concomitant small vascular lesions are common in adjacent tumor tissue and can significantly influence the overall rate of cerebrovascular disease in convalescents with diffuse gliomas.