Meningioma

1. MENINGIOMA
Dr. Ayush Garg

2. •Introduction
•Epidemiology
•Risk Factors
•Clinical Features
•Investigations
•Treatment
•Follow Up

3. INTRODUCTION
• Meningioma was first coined by Harvey Cushing (1922).
• Refers to a set of tumors that arise contiguously to the meninges.
• 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.
Meningiomas can also occur in an intraventricular or
intraosseous location. (Rare)

4. EPIDEMIOLOGY
• 2-10 cases per 100,000 individuals.
• Account for approximately 20% of all primary intracranial neoplasms.
majority are benign, with about 1%-3% classified as malignant
98% are intracranial but may arise anywhere in central nervous system
• 2.3% of individuals have undiagnosed asymptomatic meningioma on
autopsy.
• Synchronous Meningiomas in 5-40% of cases.
• Women affected twice as often as men. (1:1.4 to 1:2.8)
8.4-9.6 for women vs 2.2-3.8 for men per 100,000.
• Incidence increases with age.

5. RISK FACTORS
• Likely
First degree relative.
NF2 gene – Chromosome 22q12.2
• Merlin Protein (thought to be involved in cell-to-cell contact and motility)
• Lower expression in meningioma and loss of Merlin protein lead to
development of benign meningioma.
Exposure to ionizing radiation
• Cranial radiation associated with increased risk of meningioma and other central
nervous system tumors in survivors of childhood cancer.
• Computed tomography scans during childhood or adolescence associated with
increased risk of brain cancer.
any cancer
brain cancer

6. • Possible
HRT
Obesity
Intrathecal Methotrexate
Oral Contraceptive
• Current or past hormone replacement therapy associated with
increased risk of meningioma.
• Increased with any estradiol-only therapy.
• Increased with use of estradiol-only for ≥ 3 years.
• Not significantly affected by use of estradiol plus progestin.
• Obesity associated with increased risk of meningioma
compared to normal weight.

7. Associated Syndromes
•Hereditary syndromes associated with
meningioma include
Li-Fraumeni syndrome – AD, TP53, Sarcoma, breast,
leukaemia and adrenal gland (SBLA) syndrome.
Turcot – DNA repair, HNPCC + Brain tumour.
Gardener – Cr5q21, APC, AD
Von Hippel-Lindau – Cr3p25, AD, VHL suppresor gene
Cowden – PTEN tumour suppresor.
Gorlin – Cr9q22 PTCH1 tumour suppressor
Multiple endocrine neoplasia type I – pituitary, parathyroid,
and pancreas.

8. Cause
• Unknown
• NF2 gene – familial cases.

9. CLINICAL FEATURES

10. • Presentation depends on size and location of tumor frequent
manifestations include:
– Partial seizures (most common symptom)
– Headache
– Personality changes
– Neuropsychological deficits
– Sensory-motor symptoms
– Visual symptoms eg Foster-Kennedy
– Aphasia

11. Mechanism
• Irritation: By irritating the underlying cortex, meningiomas can cause
seizures. New-onset seizures in adults justify neuroimaging (eg, MRI) to
exclude the possibility of an intracranial neoplasm.
• Compression: Localized or nonspecific headaches are common.
Compression of the underlying brain can give rise to focal or more
generalized cerebral dysfunction, as evinced by focal weakness, dysphasia,
apathy, and/or somnolence.
• Causing reactive swelling in brain tissue surrounding the tumor

12. • Blocking the flow of the cerebrospinal fluid (CSF) (hydrocephalus) in the
brain and spinal cord resulting in its accumulation
• Blocking the flow of blood in various veins and arteries in the head by
compressing these structures or invading them.
• Others:
Meningiomas in the vicinity of the sella turcica may produce
panhypopituitarism.
Meningiomas that compress the visual pathways produce various visual field
defects, depending on their location. – e.g. Foster Kennedy syndrome

13. Location
• 85-90% supratentorial
45% parasagittal, convexities
15-20% sphenoid ridge
10% olfactory groove / planum sphenoidale
5-10% juxtasellar
• 5-10% infratentorial
• < 5% miscellaneous intracranial
intraventricular meningioma (choroid plexus)
optic nerve meningioma
pineal gland
spinal : especially thoracic
• <1% "extra dural"
sinonasal cavity : most common
intraosseous and may involve scalp
parotid gland
skin

15. IMAGING
• Meningiomas are located at any site where meninges are found.
• Modalities
X Ray
CT
MRI

16. X Ray
• X Ray no longer have a role in the diagnosis or management of
meningiomas. Historically a number of features were observed,
including:
enlarged meningeal A. grooves
hyperostosis or lytic regions
calcification

17. Computerized Tomography
CT is often the first modality employed to investigate
neurological signs or symptoms, and often is the modality
which detects an incidental lesion.
• 60% slightly hyper-dense to normal brain
• 20-30% have some calcification 8
• 72% brightly and homogenously contrast enhance 8, less frequent in
malignant or cystic variants
• Hyperostosis
otypical for meningiomas that abut the base of skull
oneed to distinguish reactive hyperostosis from skull vault invasion (eventually
involves the outer table too)
Lytic regions

19. MRI
• MRI is the investigation of choice for the diagnosis and
characterization of meningiomas.
• When appearance and location is typical, the diagnosis can be made
with a very high degree of certainty.
• Typically appear as extra-axial masses with a broad dural base. They
are usually homogeneous and well circumscribed.
Frontal view at MRI of a typical convexity
meningioma

20. Parafalx meningioma Buckling of
white matter(Thick arrow) and
Dural tail enhancement(thin
arrow)
Dural tail
CECT
MRI:POST CONTRAST AXIA & SAGITTAL:
Sphenoid wing meningioma
Cisterns are widened(thick arrow)
& Dural tail enhancement(Thin arrow)
EXTRAAXIAL SOLS: MENINGIOMAs, Dural tail enhancement& widened
cisterns

21. PET-CT Scan
• There is no established role of PET-CT Scan

22. Pathology

23. Macroscopic Microscopic
In general there are two main
macroscopic forms: globose and en
plaque.
• Globose are rounded, well defined
dural masses, likened to the
appearance of a fried egg seen in
profile.
• En plaque meningiomas on the
other hand are extensive regions
of dural thickening.
• Arise from meningothelial arachnoid
cells
• Histological sub types include
Transitional
Fibroblastic
Syncytial
Psammomatous
Secretory
Microcytic
Papillary and rhabdoid : have a
propensity to recur

24. HISTOLOGICAL GRADING
• WHO grading 1993, 2000, 2007:
• WHO 1 meningioma : 80-90%
• Varying rates of progression to higher grade
• 7%-20% recurrence rate
• Pathologic features include
• Pleomorphic,
• Occasional mitotic figures,
• Absence of pathologic features found in atypical or anaplastic
meningiomas
• Histologic types include
• Meningothelial,
• Psammomatous,
• Secretory,
• Fibroblastic,
• Angiomatous,
• Lymphoplasmacyte rich,
• Transitional,
• Microcytic,
• Metaplastic

25. • WHO 2 atypical meningioma (atypical, clear cell,
chordoid) : 5-15 %
• 30%-40% recurrence rate
• Pathologic features include any of
• 4 mitotic figures per 10 high-power fields of 0.16
mm2
• 3 of (a) increased cellularity, (b) small cells with
high N:C ratio, (c) prominent nucleoli, (d) sheet-like
growth, (e) necrosis
• Brain invasion

26. • WHO 3 malignant meningioma (rhabdoid, anaplastic, papillary) :
1-3 %
• 50%-80% recurrence rate
• pathologic features require 20 mitotic figures per 10 high-power
fields of 0.16 mm2 or frank anaplastic features

27. TREATMENT

28. Overview
• Treatment depends on meningioma size and location, and on
patient age, symptoms, comorbidities, health status, and treatment
preference
• Conservative management, consisting of observation with close
monitoring of clinical and disease status, may be option for
patients with asymptomatic meningioma

29. • For patients with symptomatic meningioma, or with asymptomatic
progressively enlarging tumors, complete surgical resection
recommended, where possible
• Alternative options include
Partial surgical resection plus radiation therapy
Radiation therapy
• For patients with inoperable or recurrent meningioma after surgery
or radiation therapy, medical therapies may be tried but have
limited and inconsistent evidence of efficacy

30. Treatment Modalities
The available treatment
modalities are-
Observation Surgery Radiotherapy Chemotherapy

31. Selecting treatment modality
• Meningioma treatment approach treatment of asymptomatic meningioma
 For lesions < 3 cm (long axis), options include
Observation
Surgery for tumor with potential neurologic consequences if
accessible, followed by radiation therapy for world health organization
(WHO) grade III tumor or for subtotal resection of WHO grade II
tumor
Radiotherapy for tumor with potential for neurologic consequences
 For lesions > 3 cm, options include
Surgery if tumor is accessible followed by radiotherapy if tumor is
WHO grade III, and consider radiotherapy if resection is incomplete
and tumor is WHO grade I or II
Observation

32. • Treatment of symptomatic meningioma
 For lesions < 3 cm, options include
Surgery if tumor is accessible, followed by radiotherapy for
WHO grade III tumors
Radiotherapy
 For lesions > 3 cm, options include
Surgery if tumor is accessible, followed by radiotherapy for
WHO grade III tumors, and consider radiotherapy for
incomplete resection of WHO grade I or II tumors
Radiotherapy

33. • Treatment options for recurrent meningioma include
Surgery if accessible, or radiotherapy
Additional radiotherapy if tumor not surgically accessible
Chemotherapy if tumor not surgically accessible and additional
radiotherapy not possible

34. Medical
• Indications of Medical Therapy
 Malignant tumors,
 Inoperable tumors,
 Patients not candidates for surgery, or
 When other treatment options have been exhausted
• Types:
Chemotherapy
Hormonal therapy for unresectable or recurrent meningioma
Other
Somatostatin receptor agents
Targeted molecular agents for recurrent or progressive
meningioma

35. Chemotherapy
• Hydroxyurea
• Patients with progression of World Health Organization (WHO)
Grade II or III meningioma treated with hydroxyurea reported
to have median 2 months progression-free survival.
• Cyclophosphamide, Adriamycin, and Vincristine (CAV)
• Patients with malignant meningioma treated with CAV
chemotherapy following surgery and radiation therapy reported
to have median survival 5.3 years

36. Hormonal Therapy
• Tamoxifen reported to improve or stabilize refractory unresectable
meningioma in some patients
• Mifepristone reported to improve tumor size or visual field in
some patients with unresectable meningioma
• Patients with refractory recurrent meningioma treated with
temozolomide reported to have median survival 7.5 months

37. Other Agents
Somatostatin Analogues
• Patients with recurrent WHO grade II or III meningioma treated
with octreotide reported to have median 4.2 months to progression
• Patients with recurrent or progressive unresectable meningioma
treated with octreotide reported to have median 17 weeks to
progression
• Patients with progressive recurrent meningioma treated with 90y-
edotreotide radionuclide therapy reported to have median survival
69 months for WHO grade I tumors and 30.5 months for WHO
grade II-III tumors

38. Interferon α
• Patients with progression of WHO grade I unresectable
meningioma treated with interferon alpha reported to have median
survival 8 months

39. • Targeted molecular agents for recurrent or progressive
meningioma
• Patients with recurrent meningioma following surgery and
radiation therapy treated with Imatinib (tyrosine kinase inhibitor)
600-800 mg/day reported to have median progression-free survival
of 2 months in case series of 23 patients.
• Patients with recurrent meningioma treated with an epidural
growth factor inhibitor, Gefitinib or Erlotinib, reported to have
median overall survival of 23 months.

40. Seizure Prophylaxis
Prophylactic antiepileptic drugs may not be effective for prevention
of seizures in patients having craniotomy
• Systematic review of 6 randomized trials evaluating prophylactic treatment
with antiepileptic drugs in 1,398 patients without epilepsy having craniotomy
• Comparing phenytoin to placebo or no treatment
• Phenytoin significantly reduced early seizures (< 1 week postoperatively) in 1 of 4 trials
• No significant differences in late seizures in 3 of 3 trials
• No significant differences in any outcomes comparing other antiepileptics vs.
No treatment or comparing different antiepileptics

41. Surgery

42. Simpson Grading 1957
• Grade I
complete removal including resection of underlying bone and associated
dura
9% symptomatic recurrence at 10 years
• Grade II
complete removal and coagulation of dural attachment
19% symptomatic recurrence at 10 years
• Grade III
complete removal w/o resection of dura or coagulation
29% symptomatic recurrence at 10 years
• Grade IV
subtotal resection
44% symptomatic recurrence at 10 years
• Grade V
decompression with or without biopsy
100% symptomatic recurrence at 10 years (small sample in original paper)

43. Embolization
• Preoperative embolization of meningioma to minimize intraoperative
bleeding
• Embolization may be an alternative primary treatment of
meningioma for patients not candidates for craniotomy and surgical
resection. - Reported associated with marked tumor shrinkage over
20 months.

44. Radiotherapy

45. Overview
• Conventional radiation therapy
• Stereotactic radiosurgery
Gamma Knife
Cyber Knife
• Fractionated stereotactic radiosurgery
• Intensity-modulated radiation therapy (IMRT)

46. Indications/Side effects
• Primary treatment for inoperable meningioma or for patients for whom
surgery would be inappropriate
follow-up treatment for patients with incomplete resection of meningioma
• Complete tumor eradication not possible but tumor shrinkage reported
• Treatment to dose of 54 Gy for Grade I and 60 Gy for Grade II-III.
• Complications of radiation therapy may include
Alopecia
Tooth loss
New onset seizures
Neurological deficits
Cranial nerve palsy
Headache
Edema
Radio-necrosis
Delayed hydrocephalus

47. Conventional – Whole Brain Radiotherapy
• Conventional radiation therapy used to treat incompletely resected
meningioma, or treat patients for whom surgery is inappropriate
• Addition of radiation therapy to partial resection may not improve
overall survival but may reduce tumor progression in patients with
WHO Grade I cerebral meningioma.
5-year progression-free survival91% for partial tumor resection plus radiation therapy
vs. 38% for partial tumor resection alone (p = 0.0005)
77% for total tumor resection vs. 52% for partial tumor resection with or without
radiation therapy (p = 0.02)
65% overall

48. • Whole-brain irradiation is administered through parallel-opposed
lateral portals. The inferior field border should be inferior to the
cribriform plate, the middle cranial fossa, and the foramen magnum,
all of which should be distinguishable on simulation or portal
localization radiographs.
• The safety margin depends on penumbra width, head fixation, and
anatomic factors but should be at least 1 cm, even under optimal
conditions.
• A special problem arises anteriorly because sparing of the ocular
lenses and lacrimal glands may require blocking with margins <5 mm
at the cribriform plate.

49. • The anterior border of the field should be approximately 3 cm
posterior to the ipsilateral eyelid for the diverging beam to exclude
the contralateral lens. However, this results in only approximately
40% of the prescribed dose to the posterior eye.
• A better alternative is to angle the beam approximately 3 degrees or
more (100- or 80-cm source-to-axis distance midline, but also field
size dependent) against the frontal plane so that the anterior beam
border traverses posterior to the lenses (approximately 2 cm
posterior to eyelid markers).
• Placing a radiopaque marker on both lateral canthi and aligning the
markers permits individualization in terms of the couch angle.
• This arrangement provides full dose to the posterior eyes. However,
the eyelid-to-lens and eyelid-to-retina topography is individually
more constant than the canthus, and lateral beam eye shielding is
better individualized with the aid of CT or MRI scans.
• When in doubt about tumor coverage or lens sparing for tumors in a
subfrontal or middle cranial fossa location, one should consider CT-
based contouring and planning.

52. SRS
• Stereotactic radiosurgery (SRS) may be alternative to external beam
radiation in patients with recurrent or partially resected
meningiomas < 35 mm in diameter
• Contraindications to surgery due to comorbidities or tumor location
• Skull base tumors of small or moderate size, for which surgical
resection carries greater risk
• Allows larger radiation doses to be delivered more accurately and
limits radiation exposure to surrounding tissue.

54. Fractionated SRS
• Fractionated stereotactic radiation therapy spares normal tissue
sensitive to hypofractionation.
• Preferred treatment of optic nerve sheath meningioma.

55. Examples of radiation therapy planning of
(A) stereotactic radiosurgery as a salvage therapy for a patient
with recurrent meningioma,
(B) fractionated stereotactic radiotherapy as a definitive
therapy for a patient with unresectable tumor due to a high
risk of cranial nerve damage after a surgery and
(C) 3-dimensional conformal radiotherapy as a postoperative
radiotherapy for a patient with residual tumor after surgical
resection.

56. Gamma Knife
Based on case series of 4,565 patients with 5,300 benign meningiomas
• 10-year progression-free survival 88.6% and 5-year progression-free survival
95.2%
• Permanent morbidity rate at last follow-up 6.6%
• Tumor volume after treatment
Decreased in 58%
Unchanged in 34.5%
Increased in 7.5%
Gamma knife stereotactic radiosurgery as primary treatment for
cavernous sinus meningiomas may be associated with better
neurologic recovery than surgical resection with adjuvant radiosurgery.

57. The scans below show a patient with meningioma
The scans below show the same patient with meningioma SIX
MONTHS after gamma knife treatment.

58. Cyber Knife
Multisession Cyber Knife radiosurgery for a petrosal meningioma in a patient
affected by multiple sclerosis.

59. IMRT
• IMRT is computer optimized 3D conformal tumor localization with
computer-controlled radiation intensity modulation
• Appropriate for tumors that are irregularly shaped and too large for
stereotactic radiosurgery.

61. Emerging Role of Proton Therapy

62. Radiation oncologists at the Roberts Proton Therapy Center are
conducting a Phase II clinical trial to ascertain the feasibility of
proton therapy as an adjunct to surgery for WHO Grade I-III
meningiomas and hemangiopericytomas.
This study seeks to assess the effect of proton therapy on rates of
acute toxicity, fatigue and quality of life in the same population. The
frequency of recurrence and long term toxicity will also be
evaluated.

63. The Most Significant Benefits of Proton
Therapy
• Causes fewer short- and long-term
side effects
• Proven to be effective in adults and
children
• Targets tumors and cancer cells
with precision, reducing the risk of
damage to surrounding healthy
tissue and organs
• Reduces the likelihood of secondary
tumors caused by treatment
• Treats recurrent tumors, even in
patients who have already received
radiation
• Improves quality of life during and
after treatment

64. Study Compares Effects of X-ray Radiation with
Proton Therapy
• A study analyzed patients
treated with X-ray radiation and
compared them with patients
treated with proton therapy.
• Of the patients treated with X-
ray radiation, 12.8% developed
secondary cancers caused by
treatment, while only 6.4% of
the proton therapy patients
developed secondary cancers.

65. Follow up and Prognosis

66. Follow up
• No standard guidelines for follow-up.
• For symptomatic patients, individualize follow-up based on tumor grade,
previous treatment, and remaining treatment options
Consider first magnetic resonance imaging 3-6 months after surgery or
radiotherapy
Perform subsequent magnetic resonance imaging (MRI) every 6 months for 2
years in clinically stable patients, and then every year as indicated, and
thereafter, every 2 years
For patients with atypical or malignant meningioma, MRI every 3 months during
first year and subsequently as for malignant brain tumors
• For asymptomatic meningioma
Observation with close clinical and radiological follow-up
Serial volumetric measurements of tumor are useful, especially in younger
patients with greater potential for tumor growth

67. Prognosis
• Median patient survival reported as:
 10 years for WHO grade I meningioma
 11.5 years for WHO grade II meningioma
 2.7 years for WHO grade III meningioma
• Patients with meningioma have reduced survival compared to
general population.
 Compared to population without meningioma, meningioma associated with83% 1-year
relative survival rate
 71% 15-year relative survival rate
• 5-year survival rate:
 81% for patients aged 21-64 years and 56% for patients ≥ 65 years old
• Larger tumor size at presentation and faster tumor growth rate
might be associated with new or worsening symptoms in patients
with untreated meningiomas
 4% with tumor diameter < 2 cm, 17% with tumor diameter > 2.5 to 3 cm
 0% with tumor diameter 2-2.5 cm growing at ≤ 10% per year AND42% with tumor
diameter 2-2.5 cm growing at ≥ 10% per year

68. • For benign meningiomas, factors independently associated
with longer survival included:
female sex, Caucasian race, surgery, small tumor size, no radiation
treatment, skull base tumor, and treatment at community
hospitals
• For malignant meningiomas, factors independently
associated with longer survival included:
Younger age at diagnosis, female sex, surgery, no radiation
treatment, and ≥ 800 new cancer cases seen per year by the
treating hospital

69. THANK YOU