Gliomas are diffusely infiltrating brain tumors whose prognosis is strongly influenced by their extent of invasion into the surrounding brain tissue. While lower-grade gliomas present more circumscribed borders, high-grade gliomas are aggressive tumors with widespread brain infiltration and dissemination. Glioblastoma (GBM) is known for its high invasiveness and association with poor prognosis. Its low survival rate is due to the certainty of its recurrence, caused by microscopic brain infiltration which makes surgical eradication unattainable. New insights into GBM biology at the single-cell level have enabled the identification of mechanisms exploited by glioma cells for brain invasion. In this review, we explore the current understanding of several molecular pathways and mechanisms used by tumor cells to invade normal brain tissue. We address the intrinsic biological drivers of tumor cell invasion, by tackling how tumor cells interact with each other and with the tumor microenvironment (TME). We focus on the recently discovered neuronal niche in the TME, including local as well as distant neurons, contributing to glioma growth and invasion. We then address the mechanisms of invasion promoted by astrocytes and immune cells. Finally, we review the current literature on the therapeutic targeting of the molecular mechanisms of invasion.

Pediatric high-grade glioma (pHGG) encompasses a wide range of gliomas with different genomic, epigenomic, and transcriptomic features. Almost 50% of pHGGs present a mutation in genes coding for histone 3, including the subtype harboring the H3.3-G34 mutation. In this context, histone mutations are frequently associated with mutations in TP53 and ATRX, along with PDGFRA and NOTCH2NL amplifications. Moreover, the H3.3-G34 histone mutation induces epigenetic changes in immune-related genes and exerts modulatory functions on the microenvironment. Also, the functionality of the blood–brain barrier (BBB) has an impact on treatment response. The prognosis remains poor with conventional treatments, thus eliciting the investigation of additional and alternative therapies. Promising molecular targets include PDGFRA amplification, BRAF mutation, EGFR amplification, NF1 loss, and IDH mutation. Considering that pHGGs harboring the H3.3-G34R mutation appear to be more susceptible to immunotherapies (ITs), different options have been recently explored, including immune checkpoint inhibitors, antibody mediated IT, and Car-T cells. This review aims to summarize the knowledge concerning cancer biology and cancer-immune cell interaction in this set of pediatric gliomas, with a focus on possible therapeutic options.

Background: Meningoencephalocele is defined as an abnormal sac of brain tissue and meninges extending beyond natural skull margins, often leading to cerebrospinal fluid (CSF) leakage. When this condition arises in the spheno-ethmoidal region, the diagnosis becomes more challenging as it can be mistaken for other nasal pathologies, such as mucocele. Research question: We show in this case report a non-congenital sphenoethmoidal meningoencephalocele causing rhinoliquoral fistula and spontaneous intracranial hypotension. Results: this 65-year-old woman presented with sporadic rhinoliquorrhoea associated with orthostatic headache , nausea and dizziness. Brain MRI revealed a small lesion of an ethmoidal sinus , which was successfully treated with endoscopic endonasal surgery. Histology confirmed the presence of meningoencephalic tissue positive for S100 protein on immunohistochemistry. Conclusions: When dealing with lesions of the paranasal sinuses in contact with the anterior skull base , rhinoliquorrhoea presence suggests meningoencephalocele. In dubious cases, a proper workup, including a thorough clinical history and neurological examination, specific imaging, and a direct search of CSF-like markers, is essential to support the differential diagnosis. In such cases, a transnasal endoscopic surgical approach is recommended to obtain a final histological diagnosis and to perform eventual dural plastic surgery.