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MAWRIN, CHUNG, AND PREUSSER
Biology and Clinical Management Challenges in Meningioma
Christian Mawrin, MD, Caroline Chung, MD, FRCPC, and Matthias Preusser, MD
OVERVIEW
Meningiomas are the most frequently occurring intracranial tumors. They are characterized by a broad spectrum of histopathologic
appearance. Molecular alterations driving meningioma development, which affect the NF2 gene, are found in roughly 50% of patients.
Rare genetic events in benign meningiomas are mutations in TRAF7, KLF4, AKT1, and SMO; all of these mutations are exclusive of NF2
alterations. Progression to a clinically aggressive meningioma is linked to inactivation of CDKN2A/B genes, and a plethora of signaling
molecules have been described as activated in meningiomas, which supports the concept of successful clinical use of specific inhibitors.
Established treatments include surgical resection with or without radiotherapy delivered in a single fraction, a few large fractions
(radiosurgery), or multiple fractions (fractionated radiotherapy). For recurrent and aggressive tumors, inhibitors of the vascular
endothelial growth factor (VEGF) pathway, such as vatalinib, bevacizumab, and sunitinib, showed signs of activity in small, uncontrolled
studies, and prospective clinical studies will test the efficacy of the tetrahydroisoquinoline trabectedin and of SMO and AKT1 inhibitors.
Meningiomas are tumors that arise from meningeal
coverings of the brain and spinal cord. According to
current epidemiologic data, they are the most common intracranial
tumors, with an incidence of 7.7 per 100,000. Meningiomas
are tumors of older populations, with a clear
increase in incidence after the age of 65. 1 They preferentially
affect women, with a female:male ratio of 3.5:1. 2 Meningiomas
in children are exceptionally rare. Risk factors other than
age include exposure to ionizing radiation, 3 the presence of
diabetes mellitus or arterial hypertension, and, possibly,
smoking; the use of mobile phones does not seem associated
with an increased tumor risk. 4-6
CLINICAL PRESENTATION AND RISK FACTORS
Approximately 90% of meningiomas develop from the cranial
meninges, although 10% occur in the spinal meninges.
The clinical presenting symptoms reflect the anatomic region
that is involved and compressed by tumor or peritumoral
edema. In many cases, patients with small meningiomas are
asymptomatic, and the tumors are found incidentally as a result
of imaging for other purposes.
Some patients may present with multiple meningiomas.
Among these cases, approximately 1% of multiple occurrences
is associated with NF2, and 4% of these cases are unrelated
to NF2. 7 Hereditary meningiomas in adults are highly
associated with NF2 alterations (see below), and 50% to 75%
of patients with neurofıbromatosis type 2 (NF2) develop meningiomas
during their lifetime. 8 Meningioma development
in other familial tumor syndromes is uncommon.
PATHOLOGY AND DIFFERENTIAL DIAGNOSES
Meningiomas originate from arachnoidal cap cells, which
form the outer layer of the arachnoid mater and the arachnoid
villi; the villi are responsible for cerebrospinal fluid
(CSF) drainage into the dural sinuses and veins. Arachnoidal
cap cells can appear either as a single fıbroblast-like cell layer
or as epitheloid nests that form several layers. Embryonically,
the meninges at the skull base are derived from the mesoderm,
and the telencephalic meninges are derived from the
neural crest. 9 With age, arachnoidal cap cell clusters become
increasingly prominent, forming whorls and psammoma
bodies identical to those found in meningiomas. On the basis
of cytologic and functional similarities to meningioma cells,
arachnoidal cap cells are favored as the most likely cell of
origin. 10
As the neoplastic counterpart of cap cells, meningiomas
can have both mesenchymal and epithelial features, reflected
by the histopathologic appearance of the most frequent meningioma
subtypes (Table 1). Approximately 80% are World
Health Organization (WHO) grade 1 meningiomas, which
consist mainly of meningothelial, fıbrous, or mixed (transitional)
tumors. There is a preponderance of specifıc intracranial
sites affected by meningiomas in association with certain
histopathologic subtypes. Meningothelial (epithelial) meningiomas
are frequently found at the skull base, whereas fı-
From the Department of Neuropathology, Otto-von-Guericke University, Magdeburg, Germany; Department of Radiation Oncology, University of Toronto/Princess Margaret Cancer Centre, Toronto,
Canada; Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Disclosures of potential conflicts of interest are found at the end of this article.
Corresponding author: Matthias Preusser, MD, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria;
email: matthias.preusser@meduniwien.ac.at.
© 2015 by American Society of Clinical Oncology.
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