MENINGIOMA

TENGKU RIZKY ADITYA, MD

INTRODUCTION

• Meningiomas are slowly growing neoplasms thought to arise from meningothelial cells found
within arachnoid granulations. Concentrated in the walls of the major venous sinuses, these
structures, which contain “arachnoid cap cells,” account for the dural localization of most
meningiomas within the cranium and spinal cord. Meningiomas may originate in any location
where arachnoidal cells are present, including the choroid plexus (intraventricular
meningioma). Meningiomas may also occur as a flattened sheath of tumor, taking the shape
of the underlying bone. This so-called meningioma en plaque is more common in the area of
the sphenoid bone.
• Most meningiomas are well-defined, lobulated, firm masses that compress the underlying
brain. Gross total resection is usually curative. Invasion of brain parenchyma is associated
with a greater likelihood of recurrence. In contrast, invasion through the dura into the
overlying cranial bone is quite common in low-grade (WHO grade I) meningioma.
• Arachnoid
• The arachnoid and the pia mater form the leptomeningeal, or thin layer of meninges.
Immediately deep to the dural border cell layer sits the arachnoid barrier cell layer. This layer
consists of tightly packed large fibroblasts with minimal extracellular space and absence of
collagen. There is a unique abundance of cell junctions. Tight junctions among cells
strengthen the arachnoid barrier cell layer and render it impermeable to fluids, large
molecular weight substance, and even some ions. In addition, a continuous basement
membrane lines the inner surface of the arachnoid, abutting the subarachnoid CSF space.
Arachnoid trabecular cells are specialized fibroblasts with long processes and attachment to
the arachnoid barrier layer. They bridge the subarachnoid space with their long, flattened,
irregular processes and may form cellular attachments with pial cells. Collagen may be found
within the trabecular matrix created by the processes in the subarachnoid space.
ARACHNOID VILLI/GRANULATIONS

• Arachnoid villi are specialized segments of the meninges that project into the sinuses and
major venous structures. They are essential in the absorption of CSF through both passive
and active mechanisms. Whereas arachnoid villi are microscopic, arachnoid granulations are
visible to the naked eye, and Pacchionian bodies are especially large, elaborate complexes.
• Arachnoid cap cells are derived from the outer portions of the endomeninx and are
considered the cells of origin of meningiomas. Although they can be located throughout the
central nervous system, including within the ventricles, the sylvian fissure, and the pineal
region, they are found in greatest concentration adjacent to the major sinuses, large cerebral
veins, and basilar plexus, and around the crista galli, over the cribriform plate, and at the exit
foramina of cranial nerves II through VII and IX through XII.
EPIDEMIOLOGY

• Meningiomas account for 20% of all intracranial tumors in males and 38% in
females, yet little is known regarding the risk factors associated with these
lesions. Data from the Central Brain Tumor Registry of the United States
(CBTRUS) reveal an age-adjusted incidence rate (per 100,000 person-years) of
8.36 and 3.61 for females and males.
• Age-Specific Incidence Rates for Meningioma in the United States (2002–
2006)
Age 0–19 20–34 35–44 45–54 55–64 65–74 75–84 85+
Rate 0.11 1.05 3.72 7.62 12.39 20.58 29.40 34.94
ETIOLOGY / RISK FACTORS

• Ionizing Radiation
In one of the most well-known studies to date of IR and meningioma risk, children who were
given radiation therapy for scalp ringworm in Israel between 1948 and 1960 (the Tinea Capitis
Cohort) were observed to have a relative risk of almost 10 for meningioma. Radiation therapy
for intracranial tumors has also been linked to meningioma risk, and animal studies support the
contention that IR can induce intracranial tumors, including meningiomas, by damaging DNA.
Several studies have linked the number of full-mouth dental radiographs to risk of meningioma,
although the sample sizes are limited, and most later studies (also small in size) did not confirm
these findings. The most recent casecontrol study of 200 meningioma patients reported that the
full-mouth series was associated with a significantly increased risk of meningioma although
evidence for a dose response relation was lacking.
• Hormones
The presence of estrogen, progesterone, and androgen receptors on some meningiomas; an
association between breast cancer and meningiomas; indications that meningiomas change in size
during the luteal phase of the menstrual cycle and pregnancy; and in vitro proliferation of
meningioma-cell lines in culture after exposure to estrogens has been observed.

• Head trauma
Head trauma has been suggested as a risk factor for meningioma, although the results across
studies are not consistent. Although several small case-control studies from the early 1980s report
an increased risk of meningioma associated with head trauma for both males and females, other
studies report no such association. A cohort study of 228,055 Danish residents hospitalized for
concussion, skull fracture or other head injury between 1977 and 1992 did not find any significant
increase in the incidence of meningioma, although the mean follow-up was only 8 years.
• Viruses
Some researchers have looked into a possible viral cause of meningiomas. One strong contender
is the Inoue-Melnick virus (IMV), a DNA virus linked to subacute myelo-opticoneuropathy. In
work reported by Inoue,77 IMV was isolated from six of seven human meningioma-derived cell
cultures but was not isolated from six other brain tumor cell cultures. The prevalence of the IMV
antibody in healthy Japanese adults was 17.3%. Of 26 patients with meningioma, 22 (84.6%)
were positive for the IMV antibody. Based on their review of the subject, however, Rachlin and
Rosenblum78 stated that “although there is strong biochemical evidence associating DNA tumor
viruses with human meningiomas, the role of the virus in the development of the tumor
remains undefined.”
• Other risk factors
- Cell phone use
- Breast cancer
- Industry/occupation/diet/allergy
- Family history of meningioma
RADIOLOGY FINDINGS

Plain radiographs reveal three characteristic findings in meningioma patients:

- Hyperostosis
- Increased vascular markings
- Calcification
RADIOLOGY FINDINGS

• Meningiomas typically isodense to slightly hyperdense compared with normal brain

parenchyma on CT, although the difference is small and these tumors can be difficult to
differentiate from adjacent cortex on a non–contrast-enhanced examination. The tumor is
sharply marginated and is usually broadly based against a bony structure or dural margin. A
common bony manifestation is hyperostosis, where they appear as thickening of the cortex,
widening of inner and outer tables, bony exostosis, or enlargement of aerated sinuses.
• The amount of edema surrounding a meningioma is variable. The dura mater adjacent to the
attachment of a meningioma may enhance on CT or MRI after the administration of a
contrast agent.
• On MRI, meningiomas are typically isointense on T1-weighted images relative
to gray matter, are slightly hyperintense on T2-weighted images, and
demonstrate avid enhancement.
• A widely discussed feature of meningiomas is the dural tail, which represents
contrast enhancement extending along the dural margins. The histologic
composition of such dural tails is not entirely clear, with evidence supporting
either meningioma involvement or reactive dural thickening.
DURAL TAIL
(A) A THIN RIM OF LOW ATTENUATION REPRESENTS CEREBROSPINAL FLUID (CSF) TRAPPED AROUND A
LARGE LEFT FRONTAL MENINGIOMA. THIS IS A FEATURE INDICATING THE EXTRAAXIAL NATURE OF
THE TUMOR. NOTE THE VASOGENIC EDEMA IN ADJACENT BRAIN PARENCHYMA (LOW DENSITY)
OUTSIDE THE CSF CLEFT (ARROWS).
(B) MENINGIOMA CENTERED IN THE RIGHT SPHENOID WING WITH EXTENSION INTO THE RIGHT
LATERAL ORBIT. THERE IS RESULTANT DEVIATION OF THE OPTIC NERVE AND MUSCLES WITH
PROPTOSIS OF THE GLOBE. THERE IS ASSOCIATED HYPEROSTOSIS OF THE SPHENOID WING, LATERAL
ORBITAL WALL, AND SQUAMOSAL TEMPORAL BONE.
MENINGIOMA CLASSIFICATION
Meningothelial meningioma
Fibrous (fibroblastic) meningioma
Transitional (mixed) meningioma
Psammomatous meningioma
WHO Grade I Angiomatous meningioma
(Benign) Microcystic meningioma
Secretory meningioma
Lymphoplasmacyte-rich meningioma
Metaplastic meningioma

Chordoid meningioma
WHO Grade II Clear cell meningioma
(Atypical)
Atypical meningioma
Papillary meningioma
WHO Grade Rhabdoid meningioma
• The distribution of intracranial meningiomas is approximately as follows:
convexity (35%), parasagittal (20%), sphenoid ridge (20%), intraventricular (5%),
tuberculum sellae (3%), infratentorial (13%), and others (olfactory groove,
cerebellopontine angle, etc) (4%).
OBSERVATION FOR MENINGIOMAS

• It is our practice to monitor patients with asymptomatic meningiomas (including those at the
skull base) and reserve treatment for patients who develop symptoms or whose tumors are
shown to grow progressively. Our follow-up strategy involves first imaging at 3 months to
exclude rapidly enlarging tumors and then at 9 months, and yearly thereafter. If the patient
remains stable for 5 years, imaging can be spread out to a biannual schedule. As part of this
strategy, it is critical to compare follow-up scans with the earliest images possible rather than
with immediately subsequent scans, to avoid missing significant changes that have occurred
over time. If at any time during this period the patient becomes symptomatic or the tumor
grows progressively, we believe that he or she should be treated with maximal surgical
resection.
OBSERVATION FOR MENINGIOMAS

• There are two exceptions to this strategy. The first is patients

harboring tuberculum sellae meningiomas, because they can
develop visual deterioration rapidly, even with small tumors.100
The other exception is young patients, because meningiomas have
been shown to grow more rapidly in these individuals, and they
are at risk for a prolonged period.
SURGICAL THERAPY AND TUMOR
RECURRENCE
• The only definitive cure for meningioma is complete surgical resection. The
more complete the resection, the less chance there is of recurrence.
• In 1957, Simpson introduced a five-grade classification of the surgical removal
of meningiomas. Recurrence rates for grade I are about 10%; those for grade
II are twice as high. The rates of recurrence are understandably higher in the
higher Simpson grades. The inclusion of an additional 2-cm dural margin has
been denoted grade 0 removal.102 In one study, no recurrences were seen in
patients with convexity meningiomas in whom grade 0 resection was
achieved; the mean followup period was 5 years and 8 months.
SYMPSON GRADING SYSTEM

Grade Description
I Macroscopically complete tumor removal with excision of the tumor's
dural attachment and any abnormal
bone
• Simpson
II Grading System
Macroscopically complete tumor removal with coagulation of its dural
attachment
III Macroscopically complete removal of the intradural tumor without
resection or coagulation of its dural
attachment or extradural extensions
IV Subtotal removal of the tumor
V Simple decompression of the tumor
LOCATION

• The anatomic location of a meningioma influences its rate of recurrence.

Tumors that are more difficult to remove totally, such as meningiomas of the
sphenoid wing, recur more often. Meningiomas that invade a dural sinus,
such as parasagittal meningiomas, have a high rate of recurrence. The
recurrence rates of meningiomas differ from one series to another; the
highest recurrence rates (>20%) are found in patients with sphenoid wing
meningiomas, followed by those with parasagittal meningiomas (8% to 24%).
The recurrence rate for convexity and suprasellar meningiomas is 5% to 10%.
LOCATION
Convexity meningioma

Parasagittal meningioma
• Sphenoid wing meningioma

• Falcine meningioma
• Suprasellar meningioma

• Olfactory groove meningioma

RADIATION THERAPY
Nonsurgical therapies are used for recurrent or incompletely resected meningiomas. Standard
or stereotactic irradiation has been used. Acknowledging that the potential benefits of
radiotherapy should always be balanced against its known side effects and complications,
Guthrie and associates concluded that “while surgical excision is the treatment of choice,
radiation therapy should be considered:
(1) after surgery for a malignant meningioma
(2) following Incomplete resection of a meningioma for which the risk of resection of an
eventual recurrence is judged to be excessive
(3) for patients with multiple recurrent tumors for whom the surgeon judges repeat surgery to
be too risky
(4) as a sole therapy of a progressively symptomatic patient with a meningioma judged by the
surgeon to be inoperable.
Although the adjuvant role of stereotactic radiotherapy is gaining ground among
neurosurgeons, its use as primary treatment for poorly accessible meningiomas (e.g., cavernous
sinus or clival) is the subject of ongoing debate.
MEDICAL MANAGEMENT
The presence of hormonal receptors in meningiomas has prompted research into hormonal manipulation
as treatment.
- Tamoxifen, an estrogen antagonist, was shown to stimulate meningioma cells in culture, perhaps because
of its partial estrogen-agonistic activity.
- Oura and colleagues reported an anecdotal case of a patient with gastric carcinoma treated with
mepitiostane, an antiestrogen agent. The patient also had a presumed falcine meningioma discovered
incidentally during the metastatic work-up. The patient was treated with mepitiostane for 2 years, and
the meningioma had decreased by 73% at the end of this period.
• Bromocriptine, a dopamine antagonist, inhibits meningioma cells significantly invitro.
• Trapidil, a drug with known antagonistic action against PDGF, showed a dose dependent inhibition of
meningioma cell proliferation. Trapidil significantly inhibited the epidermal growth factor–stimulated
proliferation of meningiomas. When trapidil is administered in conjunction with bromocriptine, there is
an additive inhibitory effect on meningioma cell growth that is more pronounced than when either drug
is used alone.
THANK YOU