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Background: Meningioma is the most common primary tumor of the central nervous system and has relatively good outcomes. Rarely, meningiomas metastasize and greatly reduce the likelihood of survival. Due to its infrequency, there is little information available to inform physicians whether a meningioma patient is at-risk for experiencing metastasis. Methods: We searched PubMed, Scopus, Embase, and Ovid for studies with intracranial meningiomas metastasizing to non-CNS locations. Case reports and studies with metastasis to the spinal cord were excluded. Primary tumors were characterized based on location, recurrence, histological grade, patient sex, and overall survival. Results: Our database search yielded 1,002 unique articles, of which 6 were included in the final review. The studies yielded a total of 546 patients with high-grade meningioma. Overall, there were 23 patients from this cohort that suffered metastasis of their primary tumor (4.2%). The majority of metastatic patients were female (65.0%), and 21 patients experienced recurrence of their primary tumor, along with metastasis (91.3%). Multiple risk factors were individually analyzed by studies, including skull base location, sinus invasion, and molecular characteristics. Conclusion: Metastatic meningioma is a rare but deleterious complication. Due to its infrequent incidence, there is a paucity of literature comparing risk factors for metastasis to guide clinical decision-making. Our study summarizes the current literature available on the overall incidence of metastasis in high-grade meningiomas and highlights multiple risk factors, both clinical and molecular, that future studies should characterize to provide a more comprehensive understanding of this rare pathology.

Highly malignant brain tumors harbor the aberrant propensity for aerobic glycolysis, the excessive conversion of glucose to lactic acid even in the presence of ample tissue oxygen. Lactic acid is rapidly effluxed to the tumor microenvironment via a group of plasma-membrane transporters denoted monocarboxylate transporters (MCTs) to prevent “self-poisoning.” One isoform, MCT2, has the highest affinity for lactate and thus should have the ability to respond to microenvironment conditions such as hypoxia, lactate, and pH to help maintain high glycolytic flux in the tumor. Yet, MCT2 is considered to not respond to hypoxia, which is counterintuitive. Its response to tumor lactate has not been reported. In this report, we experimentally identify the transcription initiation site/s for MCT2 in astrocytes (normal) and glioma (tumor). We then use a BACmid library to isolate a 4.2-kbp MCT2 promoter-exon I region and examine promoter response to glycolysis-mediated stimuli in glioma cells. Reporter analysis of nested-promoter constructs indicated response of MCT2 to hypoxia, pH, lactate, and glucose, the major physiological “players” that facilitate a tumor's growth and proliferation. Immunoblot analysis of native MCT2 expression under altered pH and hypoxia reflected the reporter data. The pH-mediated gene-regulation studies we describe are the first to record H+-based reporter studies for any mammalian system and demonstrate the exquisite response of the MCT2 gene to minute changes in tumor pH. Identical promoter usage also provides the first evidence of astrocytes harnessing the same gene regulatory regions to facilitate astrocyte-neuron lactate shuttling, a metabolic feature of normal brain.