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Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin’s functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin’s cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.

Objective The purpose of this article was to provide a combined pathologic and radiologic review of previous pathologically diagnosed facial nerve “hemangiomas” to confirm that these lesions are most characteristic of venous malformations rather than neoplasms. Study Design Retrospective radiologic, clinical, and histopathologic review of all patients with a previous pathologically diagnosed facial nerve hemangioma of the temporal bone who underwent computed tomography or magnetic resonance imaging (MRI) were included. A consensus radiologic review for characteristic features and pathologic analysis was performed. Materials and Methods A panel of 4 neuroradiologists retrospectively analyzed CT and MRI exams for 11 facial nerve hemangiomas and provided a consensus agreement on the characteristic imaging features. Concurrently, two neuropathologists reevaluated archived tissue specimens from these lesions and applied additional immunohistochemical and histochemical stains including D240, CD31, smooth muscle actin (SMA), Verhoeff Van Gieson (VVG) and glucose transporter 1 (GLUT1). Results Lesions were composed of dilated vascular spaces with a simple, CD31‐positive endothelial lining and a smooth muscle component. All lesions were negative for markers found in arterial and lymphatic malformations and infantile hemangiomas. They had characteristic radiologic features previously ascribed to facial nerve hemangiomas. Namely, these lesions are typically T1 isointense or hypointense and T2 hyperintense relative to cerebral cortex and heterogeneously enhance on MRI. Bony canal expansion and erosion, intralesional calcification, and intracranial extension are common. Conclusions On the basis of this radiologic and pathologic review, these lesions are best characterized as venous malformations. Level of Evidence 4

This paper reviews a case of metastatic 1p/19q codeleted oligodendrioglioma causing diffuse osteosclerosis and pain. Primary central nervous system (CNS) tumors rarely metastasize outside the CNS, and metastatic oligodendroglioma is rarer still. The patient in this study had relief of pain after being treated with temozolomide. We discuss this rare presentation and potential treatment options, and review the literature in regards to metastatic oligodendrogliomas.

Gliosarcoma is an uncommon variant of glioblastoma, which commonly demonstrates dural attachment. However, skull base invasion is rarely seen with this entity. Herein, we report a 44-year-old female patient diagnosed with primary intracranial gliosarcoma extensively invading the skull base and muscles of mastication. She presented to our institution with a three-month history of difficult right jaw opening and retro-orbital pressure and one week of severe right-sided postauricular headache. Head CT demonstrated a 6 cm mass with marked bony erosion. Brain MRI at a one-week interval more clearly characterized tumor extension through the right orbit and muscles of mastication, with overall growth to 7 cm and worsening midline shift. The patient underwent a right frontotemporal craniotomy for gross total resection. Pathology confirmed the diagnosis of gliosarcoma, IDH-wildtype (WHO grade IV). Her postoperative course was uneventful and she was discharged at preoperative neurologic baseline. To our knowledge, this is the third reported case of a primary intracranial gliosarcoma with direct invasion of skull base, brain parenchyma, and extracranial compartment. However, this is the first report case of primary GS invading the surrounding musculature and orbit. This case report highlights the rapid aggressiveness of gliosarcomas and further a prior undescribed radiographic and anatomic finding of skull base invasion with this entity.