User:DerekvG/sandbox/braintumor/meningioma

DerekvG/sandbox/braintumor/meningioma

Meningiomas are the second most common primary neoplasm of the central nervous system, arising from the any of the 3 layers of the meninges that envelope the brain and spinal cord. These tumors are usually benign in nature; however, they can be malignant.. Meningioma is also called meligioma, mengioma, mengiomia, menigiom, menigioma. Due to their location in the meninges these tumors have characterics that makes them easier to treat then for instance Astrocytomas of similar size and at a similar location on the brain.

preamble

Meninges of the CNS

In order to understand Meningiomas we should know that the meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. A meningioma could arise in any of these layers so if it arises from the arachnoid "cap" cells of the arachnoid villi in the meninges. then the neoplasm would be "enveloped" between the other layers protecting the brain parenchyma this is a so called "wrapped" meningioma.

Meningiomas are most frequently found in women (2 out of 3 cases are women). Most people who develop a meningioma are adults. But a meningioma can occur at any age, including childhood.

There are some some exeptional form of meningioma's that we should mention here (and which are not further discussed in this lemma):

• Extra-cranial meningioma's or meningioma's with an extracranial extention : in these cases the meningioma passes through the skull and a swelling occurs on the outside of the cranium. In the articles below (readable PDF document) some very graphic images are shown of patients with enormous bulbeous growths on their skull.
  • This article discusses a case of a 55 year old man with a giant (extra-cranial) meningioma
  • This article discusses some rare case in the UK

• Intraosseous meningioma's affect the bone tissue of the skull and might cause external lumps to form on the cranium bone. This article discusses some cases of primary intraosseus meningioma

Causes

Meningiomas commonly are found at the surface of the brain, either over the convexity or at the skull base. In rare cases, meningiomas occur in an intraventricular or intraosseous location. Meningiomas occur in the cells that make up the meninges — the membranes that surround the brain and spinal cord, forming a protective barrier. consequently meningiomas may occur intracranially or within the spinal canal. They are thought to arise from arachnoidal cap cells, which reside in the arachnoid layer covering the surface of the brain.

Doctors know that something alters some cells in your meninges to make them multiply out of control, leading to a meningioma tumor. But whether this occurs because of genes you inherit, things you're exposed to in your environment or a combination of both remains largely an area for scientific speculation.

Most cases are sporadic while some are related to a genetical predisposition.

• Persons who have undergone radiation to the scalp are more at risk for developing meningiomas.
  • Patients subjected to low-dose irradiation for tinea capitis may develop multiple meningiomas decades later in the field of irradiation.
  • High-dose cranial irradiation may induce meningiomas after a short latency period.

• Female hormones. Meningiomas are more common in women, leading doctors to believe that female hormones may play a role in their development.

Dr G. Haddad writes in his article " Several findings suggest an association between hormones and the risk for meningiomas, including increased incidence in women versus men and the presence of estrogen, progesterone, and androgen receptors on some of these tumors. However, the exact nature of this relationship and its implication on the management of meningiomas remain under investigation."

• An inherited nervous system disorder. Dr G. Haddad quoted for his article says "Genetic causes have been implicated in the development of meningiomas:

• • The best-characterized and most common genetic alteration is the loss of the NF2 gene (NF2) on chromosome 22q6 . NF2 encodes a tumor suppressor known as merlin (or schwannomin)." The rare disorder neurofibromatosis type 2 seems related to in increased risk of some kinds of brain tumors and specifically linked to the occurence of meningioma.
  • "Of interest, the meningioma locus is close to but probably different from the gene responsible for NF2.
  • Up to 60% of sporadic meningiomas were found to harbor NF2 mutations.
  • Other cytogenetic alterations are chromosomal loss of 1p, 3p, 6q, and 14q.
  • Loss of chromosome 10 is associated with increased tumor grade, shortened time to recurrence, and shortened survival.
  • Progression to anaplastic meningioma has been associated with involvement of chromosomal site 17q.
  • The following events were found to be associated with higher grades of meningiomas: loss of the tumor suppressor in lung cancer-1 gene (TSLC-1), loss of progesterone receptors, increased expression of cyclooxygenase 2 and ornithine decarboxylase.
  • Monosomy of chromosome 7 is a rare cytogenetic change. However, it is frequently reported in radiation-induced meningiomas.
  • The invasive potential of meningioma cells seems to be reflected by a balance between the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs).
  • The most consistent chromosomal abnormality isolated in meningiomas is on the long arm of chromosome 22.
  • Meningiomas can also be associated with different genetic syndromes, namely Gorlin7 and Rubinstein-Taybi syndromes8 ."

Other possible genes/loci include:

• MN1
• PTEN
• an unknown gene at 1p13

Even after a full pathological examination of an individual case, the exact cause or combination of factors leading to the growth of the tumor will remain unknown for the patient and for the medical team.

Occurrance

United States

The annual incidence of symptomatic meningiomas is approximately 2 cases per 100,000 individuals. Meningiomas account for approximately 20% of all primary intracranial neoplasms. However, the true prevalence is likely higher than this because autopsy studies reveal that 2.3% of individuals have undiagnosed (asymptomatic) meningiomas. Meningiomas are multiple in 5-40% of cases, particularly when they associated with neurofibromatosis type 2 (NF2). Familial meningiomas are rare unless associated with NF2.1

International

The frequency of meningiomas in Africa is nearly 30% of all diagnosed primary intracranial tumors (in Africa intracranial neoplasms remain largely undetected because of low access to medical facilities, and low rates of post-mortem examinations).

• Ethnicity (genetically speaking) may be a factor of higher prevalence : meningiomas are more prevalent in Africa than in North America or Europe. In Los Angeles County, meningioma is reported more commonly in African Americans than in others.
• Also gender may be a factor : Meningiomas afflict adult women more often than men, but are equally distributed between boys and girls.
  • The male-to-female ratio ranges from 1:1.4 to 1:2.8. (in the US)
  • The female preponderance may be less pronounced in the population of african origin (in africa and in the US) than in other groups.
• Age might be a factor not to be neglected : the incidence increases with age.

Age bracket	Incidence (per 100.000) in 2002
0-19 years	0.12
20-34 years	0.74
35-44 years	2.62
45-54 years	4.89
55-64 years	7.89
65-74 years	12.79
75-84 years	17.04
85 years and older	18.86

Signs and symptoms

Main article: brain tumor

Signs and symptoms of a meningioma typically begin gradually and may be very subtle at first. Signs and symptoms may include:

• Changes in vision, such as seeing double or blurriness
• Headaches that worsen with time
• Hearing loss
• Memory loss, loss of attention and difficulty to focus
• Seizures
• Weakness in your arms or legs

Small tumors (e.g., < 2.0 cm) are usually incidental findings at autopsy without having caused symptoms. Larger tumors can cause symptoms depending on the size and location.

• Focal seizures may be caused by meningiomas that overlie the cerebrum
• Progressive spastic weakness in legs and incontinence may be caused by tumors that overlie the parasagittal frontoparietal region.
• Sylvian tumors may cause myriad motor, sensory, aphasic, and seizure symptoms depending on the location.
• Increased intracranial pressure eventually occurs, but is less frequent than in gliomas.

Mechanism

Meningioma fibromatous variant

Meningiomas arise from arachnoidal cells, most of which are near the vicinity of the venous sinuses, and this is the site of greatest prevalence for meningioma formation. They are most frequently attached to the dura over the superior parasagittal surface of frontal and parietal lobes, along the sphenoid ridge, in the olfactory grooves, the sylvian region, superior cerebellum along the falx cerebri, cerebellopontine angle, and the spinal cord. The tumor is usually gray, well-circumscribed, and takes on the form of space it occupies. They are usually dome-shaped, with the base lying on the dura.

Histologically, the cells are relatively uniform, with a tendency to encircle one another, forming whorls and psammoma bodies (laminated calcific concretions). They have a tendency to calcify and are highly vascularized.

Diagnosis

Meningiomas are readily visualized with contrast CT, MRI with gadolinium, and arteriography, all attributed to the fact that meningiomas are extra-axial and vascularized. CSF protein is usually elevated if lumbar puncture is attempted.

Though the majority of meningiomas are benign, they can have malignant presentations. Classification of meningiomas are based upon the WHO classification system.

Name	WHO Grade & Occurence	Hystological subtypes	Hystological features
Benign	Grade I - (90%)	Meningothelial, fibroblastic, transitional, angiomatous, microcystic, secretory, lymphoplasmacytic metaplastic, psammomatous, angioblastic (most aggressive)	does not fulfill characteristics of grade II or III
Atypical	Grade II - (7%)	choroid, clear cell, atypicia	4 or more mitotic cells per 10 hpf and/or 3 or more of the following: increased cellularity, small cells, necrosis, prominent nucleoli, sheeting, and/or brain invasion in an otherwise Grade I tumor
Anaplastic/malignant	Grade III - (2%)	papillary, rhabdoid, anaplasia	20 or more mitoses per 10 hpf and/or obviously malignant cytological characteristics such that tumor cell resembles carcinoma, sarcoma, or melanoma, occurence of necrosis

In a recent retrospective review of atypical and anaplastic meningioma cases, it was found that the mean overall survival for atypical meningiomas was 11.9 years vs. 3.3 years for anaplastic meningiomas. Mean relapse free survival for atypical meningiomas was 11.5 years vs. 2.7 years for anaplastic meningiomas.

In his article on Meningioma's dr G. Haddad describes following diagnostic procedures : "

X-ray radiography

• Plain skull radiograph may reveal hyperostosis and increased vascular markings of the skull, as well as intracranial calcifications.

CT scans

• On plain head CT scans, meningiomas are usually dural-based tumors that are isoattenuating to slightly hyperattenuating.
  • They enhance homogeneously and intensely after the injection of iodinated contrast material.
  • Perilesional edema may be extensive. Hyperostosis and intratumoral calcifications may be present.
  • The tumor compresses the brain without invading it.
  • Multiple meningiomas may be difficult to differentiate from metastasis.

T1- and T2-weighted MRI

On MRI's, the tumors have variable signal intensity. If a meningioma is suspected, obtaining an enhanced MRI is imperative.

• • Meningiomas enhance intensely and homogeneously after injection of gadolinium gadopentetate.
  • The edema may be more apparent on MRI than on CT scanning.
  • An enhancing tail involving the dura may be apparent on MRI.
  • Cystic meningiomas may exhibit intratumoral or peritumoral cysts. The peritumoral cysts may actually represent a gliotic response and may not necessitate surgical extirpation.

Angiography

• Endovascular angiography allows the surgeon to preoperatively determine the vascularization of the tumor and its encroachment on vital vascular structures.
  • Late venous images are important to determine the patency of the involved dural sinuses.
  • Angiographic features of meningiomas include the following:
    • Supply from the external circulation
    • Mother-in-law blush (which comes early and leaves late)
    • Sunburst or radial appearance of the feeding arteries
  • Although magnetic resonance arteriography (MRA) and magnetic resonance venography (MRV) have decreased the role of classical angiography, the latter remains a powerful tool for planning surgery.
  • Angiography is still indispensable if embolization of the tumor is deemed necessary.

PET-scan or MRS

• New research tools such as positron emission tomography (PET), including octreotide-PET, or magnetic resonance spectroscopy (MRS) have been used to predict in vivo the aggressiveness of meningiomas."

Treatment

A meningioma doesn't always require immediate treatment. A small meningioma that causes no significant signs and symptoms may be monitored over time for signs of growth. A meningioma that never grows may never require treatment.

Your treatment will usually be planned by a team of specialists known as a multidisciplinary team (MDT). The team will usually include a doctor who operates on the brain (neurosurgeon), a doctor who specialises in treating illnesses of the brain (neurologist), a doctor who specialises in treating cancer (an oncologist), a doctor who specialises in (anaestesist) a specialist nurse and possibly other health professionals, such as a physiotherapist or a dietitian.

There are some risks associated with treatment to the brain and your doctor will discuss these with you.

If the pressure in the skull is raised, it is important to reduce it before any treatment is given for brain tumours. Steroids may be used to reduce swelling around the tumour. If the raised pressure is due to a build-up of CSF, a tube (shunt) may be inserted to drain off the excess fluid.

Observation

If observation is the selected management for your meningioma, you'll likely have brain scans periodically to evaluate your meningioma and look for signs that it's growing. The doctor creates a personalized follow-up schedule for you. For instance, you might undergo brain scans every few months at first and then have scans done annually. If at any time your doctor determines your meningioma is growing and needs to be treated, you have several further treatment options will be discussed with you by the medical team.

Observation with close imaging follow-up can be used in select cases if a meningioma is small and asymptomatic. In a retrospective study on 43 patients, it was found that 63% of patients had no growth on follow-up, and the 37% found to have growth grew at an average of 4 mm / year. In this study, younger patients were found to have tumors that were more likely to grow on repeat imaging, thus are poorer candidates for observation.

Observation is not recommended in tumors that are already causing symptoms. Furthermore, close follow-up with imaging is required with an observation strategy to rule out an enlarging tumor.

Surgical resection

If your meningioma causes obvious symptoms or shows signs that it's growing (an active process), your medical team may recommend surgery with the objective to remove the meningioma completely (total ressection). But because a meningioma may occur near delicate structures, such as your brain, eyes and spinal cord, or in a difficultly accessible location (underneath the brain) it isn't always possible to remove the entire tumor. In those cases, surgeons remove as much of the meningioma as possible (partial ressection).

Surgery may carry a risk of significant consequences, including infection and bleeding. The specific risks of your surgery will depend on where your meningioma is located. For instance, surgery to remove a meningioma that occurs around the optic nerve can lead to vision loss.

Meningiomas can usually be surgically resected with permanent cure if the tumor is superficial on the dural surface and easily accessible. Transarterial embolization has become a standard preoperative procedure in the preoperative management. If invasion of the adjacent bone occurs, total removal is nearly impossible. Malignant transformation is rare.

The probability of tumor recurrence or growth after surgical resection can be estimated by the tumor's WHO Grade and by the extent of surgery by the Simpson Criteria.

Simpson Grade	Completeness of Resection	10-year Recurrence
Grade I	complete removal including resection of underlying bone and associated dura	9%
Grade II	complete removal + coagulation of dural attachment	19%
Grade III	complete removal w/o resection of dura or coagulation	29%
Grade IV	subtotal resection	40%

Radiosurgery

Radiosurgery is a specific type of radiation treatment that aims several beams of powerful radiation at a very precise point. Contrary to its name, radiosurgery doesn't involve scalpels or incisions. Radiosurgery may be an option for people with meningiomas that can't be removed with conventional surgery or for meningiomas that recur despite treatment.

Radiation therapy

Radiation therapy may include Gamma Knife, proton beam treatment, or fractionated external beam radiation. Gamma Knife radiosurgery can be used in lieu of surgery in small tumors located away from critical structures. Fractionated external beam radiation can also be used as primary treatment for tumors that are surgically unresectable, or for patients who are inoperable for medical reasons.

Radiation therapy is often considered for WHO Grade I meningiomas after subtotal (incomplete) tumor resections. The clinical decision to irradiate after a subtotal resection is somewhat controversial as no class I randomized controlled trials exists on the subject. Numerous retrospective studies, however, have strongly suggested that the addition of post-operative radiation to incomplete resections improves both progression free survival (i.e. prevents tumor recurrence) and improves overall survival.

In the case of a Grade II or Grade III meningioma, the current standard of care involves post-operative radiation treatment regardless of the degree of surgical resection. This is due to the proportionally higher rate of local recurrence for these higher grade tumors.

Conventional chemotherapy

Current chemotherapies are likely not effective. Antiprogestin agents have been used, but with variable results. Recent evidence that hydroxyurea has the capacity to shrink unresectable or recurrent meningiomas is being further evaluated.

consequences of treatment

A meningioma and its treatment, typically surgery followed by radiation therapy, can cause long-term complications, including:

• Difficulty concentrating
• Memory loss
• Personality changes
• Seizures

It might also cause temporary complications

• Hairloss
• Incontinence
• Tremors and epileptic seizures

In the post-operative periode and while rehabilitation certain milestones will have to be and some inconveniences might occur :

• Milestone : autonomous breathing
• Milestone : swallowing
• Milestone : intentional movement of your limbs and equilibrium (partial paralysis)
• Milestone : fine movements (hands, speech)
• Milestone : reading, unihibited speech, naming of objects, remembering key facts
• Emotional : after the surgery patients might have an flattened emotional response (this is temporary, and inhibits more pronounced reactions such as rejection, rebellion and over estimation of bodily capacities
• Uninhibited behaviour : some patients might display uninhibited behaviour (in speech, during their daily toilet etc)
• Intellectually slowed : patients will be "slowed-down" both in their ability to participate in conversation (slow to respond to questions), to express feelings or pain, generally in their responses (i.e. pain might not trigger the action to push the nurse alarm for pain treatment, but patients wait until the nurse asks them about pain), conversations with friends and family could be reduced to answering questions with a simple yes or no. Planned actions (i.e. morning wash) are difficult to repeat (patient are undecided what to do next), and simple decision hard to make (i.e. apply toothpaste before using the toothbrush, where to hang clothes if all hooks are in use).

The medical team can treat some complications (like epileptic seizures) and will either include or refer you to specialists to help you cope with other complications and to rehabilitate you both fysically or mentally.

See also

• Sphenoid wing meningioma
• Optic nerve sheath meningioma

External links

• Meningioma Information from the American Brain Tumor Association
• Meningioma information from the Mayo Clinic
• MR/CT scans of meningioma from MedPix
• MR/CT scans of pneumosinus dilatans from MedPix

• Meningioma information from the Macmillan cancer support
• Meningioma info at CancerBackup
• Meningioma article at emedicine

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