Pathological and Molecular Features of Glioblastoma and Its Peritumoral Tissue

Glioblastoma (GBM) is one of the most aggressive and lethal human brain tumors. At\r\npresent, GBMs are divided in primary and secondary on the basis of the mutational status of the\r\nisocitrate dehydrogenase (IDH) genes. In addition, IDH1 and IDH2 mutations are considered crucial\r\nto better define the prognosis. Although primary and secondary GBMs are histologically\r\nindistinguishable, they retain distinct genetic alterations that account for different evolution of the\r\ntumor. The high invasiveness, the propensity to disperse throughout the brain parenchyma, and the\r\nelevated vascularity make these tumors extremely recidivist, resulting in a short patient median\r\nsurvival even after surgical resection and chemoradiotherapy. Furthermore, GBM is considered an\r\nimmunologically cold tumor. Several studies highlight a highly immunosuppressive tumor\r\nmicroenvironment that promotes recurrence and poor prognosis. Deeper insight into the tumor\r\nimmune microenvironment, together with the recent discovery of a conventional lymphatic system\r\nin the central nervous system (CNS), led to new immunotherapeutic strategies. In the last two\r\ndecades, experimental evidence from different groups proved the existence of cancer stem cells\r\n(CSCs), also known as tumor-initiating cells, that may play an active role in tumor development and\r\nprogression. Recent findings also indicated the presence of highly infiltrative CSCs in the\r\nperitumoral region of GBM. This region appears to play a key role in tumor growing and recurrence.\r\nHowever, until recently, few studies investigated the biomolecular characteristics of the peritumoral\r\ntissue. The aim of this review is to recapitulate the pathological features of GBM and of the\r\nperitumoral region associated with progression and recurrence.