A Practical Overview on the Molecular Biology of Meningioma

Meningioma is a common intracranial neoplasm currently classified in 15 histologic subtypes across 3 grades of malignancy. First-choice therapy for meningioma is maximum safe resection for grade I tumors, and surgery plus optional and mandatory adjuvant radiotherapy for grade II and III, respectively, given the increased rate of recurrence even in the event of complete resection. The WHO 2016 histopathologic grading of meningioma has been questioned due to subjectivity and its controversial predictive power for recurrence.

Novel DNA methylation profiling has simplified classification into six classes that seem to improve prognostic accuracy. We review five main topics of molecular biology research regarding tumorigenesis and natural history of meningioma from the clinician's perspective: the histopathologic diagnostic features and pitfalls of the current tumor classification; the molecular integrated diagnosis supported by identification of genetic alterations and DNA methylation profiling; the general landscape of the various signaling pathways involved in meningioma formation; the pathogenic theories of the peri-tumoral edema present in meningioma and its therapy implications; and a summarized review on the current treatments and plausible targeted therapies directed to meningioma. It seems likely that molecular assessment will be introduced within the next update of the WHO classification of meningiomas, acknowledging the promising value of DNA methylation profiling. This integrated diagnostic protocol will simplify tumor subtype categorization and provide improved accuracy in predicting recurrence and outcome. Although much effort is being done in identifying key gene mutations, and elucidating specific intracellular signaling pathways involved in meningioma tumorigenesis, effective targeted therapies for recurrent meningiomas are still lacking.