Understanding glioma pathogenesis through ultrastructural analysis

Gliomas arise from glial cells and make up to 85% of malignant brain tumors, with an average survival of only 15 months for glioblastoma. Advances in our understanding of glioma pathogenesis and treatment require a critical analysis of the tumor ultrastructure and its microenvironment. Ultrastructural analysis (UA) using high-resolution electron microscopy enables crucial insights into the cellular and subcellular characteristics of gliomas, revealing organelle abnormalities and confirming molecular alterations. We focus on recent developments in our understanding of the ultrastructural pathology of gliomas that show the abundance of lipids found in both intracellular and extracellular environments. These lipid changes are associated with aberrant structures of mitochondria and even the disappearance of cellular membranes. Significant disruptions were also noted in tumors' blood vessels and intriguing details emerged about neovascularization and the atypical content and structure of vessel walls. In a typical display of mimicry, tumor cells replaced endothelial cells on the luminal wall of the vessels. Recent UA findings also detected multinucleated giant cells in high prevalence with the presence of extrachromosomal DNA in the microenvironment. Finally, we provide an overview of the implications of UA findings regarding future research, diagnostic modalities, and therapeutic options.