Meningioma

MRI better in delination of dura. (T2 Flair)
CT Scan better in bone remodeling and hyperostosis.


  • Sunray effect in X-ray of skull due to hyperostosis.
  • Octreotide Brain Scintigraphy
    • Meningioma has high somatostatin receptor density
  • MRI spectroscopy
    • Increase in the choline, creatine, and alanine peaks
    • A low inositol peak may distinguish a meningioma from a schwannoma.
    • A lactate peak is seen in more than 60% of atypical meningiomas.
  • Meningioma can be diagnosed radiologically and pathologic confirm

Epidemiology

  • 30% of primary intracranial neoplasms
  • Most common benign intracranial tumor in adults
  • Peak age —> 6th & 7th decades
    • Can be seen at any age
  • More common in women

General Consideration

  • Typical locations
    • Cerebral convexities
    • Falx cerebri
    • Tentorium cerebelli
    • Cerebellopontine angle
    • Sphenoid ridge

Pathology

  • Malignant varieties with invasive growth and aggressive behavior occasionally occur.
  • Grossly
    • Well-circumscribed
    • Firm, tan, or grayish lesions
    • Arising from the meninges
  • Hyperostosis of adjacent bone may be present.
  • Microscopically
    • Bland whorled appearance with little anaplasia or mitotic activity
    • Psammoma bodies may be present
  • Malignant varieties are identified on the basis of clinical behavior
    • Rapid growth
    • Recurrence
    • Invasiveness
  • Or pathologic and microscopic features of malignancy
    • Cellular or nuclear anaplasia
    • Mitotic figures
    • Specific histologic type
      • Rhabdoid
      • Papillary
      • Anaplastic

Classificantion of Meningioma

  • Grade I or benign meningiomas
    • Slow-growing
    • Well-defined borders
    • Not invading the adjacent normal brain
    • Low mitotic index
    • 90% of all meningiomas
    • Sybtypes:
      • Meningothelial (Syncytial)
      • Transitional
      • Fibrous
      • Psammomatous
      • Angiomatous
      • Microcystic
      • Secretory
      • Lymphoplasmocyte-rich
      • Metaplastic

variants (xanthomatous, myxoid, osseous,
cartilaginous)

  • Grade II or atypical meningiomas
    • Higher mitotic index (>4 mitosis per 10 HPF)
    • 5%–7% of all meningiomas
    • Sybtypes:
      • Atypical
      • Chordoid
      • Clear cell
  • Grade III or malignant meningiomas
    • Highest mitotic index (>20 per 10 HPF)
    • 1%–3% of all meningiomas
    • Subtypes:
      • Anaplastic
      • Papillary
      • Rhabdoid
Grade Mean Doubling Time 5yr Recurrence rate
I 415 3%
II 178 38%
III 205 78%

Etiology

  • Ionizing radiation
    • Interval to diagnosis of 19 to 35 years
    • Dose dependent
  • Neurofibromatosis type 2
    • Multiple
  • Hereditary predisposition to meningioma.
  • Deletion of chromosome 22
    • 50% of meningiomas have allelic losses that involve band q12 on chromosome 22
  • Allelic losses of chromosomal arms 6q, 9p, 10q, and 14q are seen in both atypical and anaplastic meningiomas

Natural history of Disease

  • Incidental finiding in CT not uncommon —> specially in older patients
  • Lesions in cerebellopontine ==> symptoms of cranial neuropathy.
    • Differential diagnosis is acoustic neuroma as may appear similar in CT and MRI
  • Cerebral convexity meningioma ==> headache / seizure
  • Sphenoid wing or optic nerve ==> visual loss.
    • Be aware of differential diagnosis of meningioma in the base of the skull or spine
      • Bone metastasis
      • Primary bone tumors
        • Chondrosarcoma
        • Chordoma
        • Osteosarcoma
  • Grow slowly
    • 14.6%/year!
      • Younger —> grow faster
      • Tumours with calcification and hypointense or isointense T2 signals on MRI grow slower

After surgery —> average time to recurrence is approximately 4 years.

Prognostic Factors:

Most Important:

  • Location of the lesion
  • Extent of surgical resection
  • Histopathologic features of the tumor
    • Benign or malignant
  • High mitotic index
  • Younger age
    • Age <40 is associated with higher incidence of recurrence
  • Male gender
  • Absence of calcification on CT scan
  • Infratentorial and petroclival location of the disease
  • Increased expression of cyclooxygenase-2 (COX-2) has been shown to be associated with more aggressive phenotypes.
  • Increased EGFR staining in malignant menigioma

Treatment

Grade I Meningioma

OBSERVATION

  • Asymptomatic

Complete surgical resection

  • Progressive benign meningiomas
  • If possible with acceptable morbidity
  • These tumour are typically vascular ==> preoperative angiography with or without embolization
  • Rate of recurrence after complete resection:
    • 5 year —>7% to 12%
    • 10 years —> 20% to 25%
  • Follow-up with serial imaging is necessary.

Subtotal resection with adj RT

Locations with more difficulty for complete resection:
  • Base of the skull
  • Cerebellopontine angle
  • Cavernous sinus meningiomas

==> Subtotal resections ==> higher relapse rates(without adjuvant therapy)

  • 5 years —> 39% to 47%
  • 10 years —> 60% to 61%
An alternative is F/U and RT reserved at time of recurrence

Radiation Technique

  • 50 - 54 Gy / 25 - 30 fr over 5 to 6 weeks
  • Target volume : defined by CT or MRI scan and modified according to the neurosurgeon's description of the location of residual tumor.
    • The margin expansion for meningiomas is based on the knowledge of direction of spread, especially through neural foramina, bony invasion, dural tails, and so forth.
    • GTV —> enhancing abnormality on contrast-enhanced MRI. Margin expansions then incorporate setup errors and block margins; these can vary from 0.5 to 1 cm
  • Multiple fields with wedges or rotational fields and 3D conformal techniques
  • Postoperative RT after incomplete resection==>
    • Improves local control
    • Prolongs the interval to recurrence
    • Improves survival
    • 10yr local control : ~90%

Barbaro Retrospective Study
All patients had subtotal resection

  • 54 patients had RT
    • > 32% recurrence
  • 30 patients surgery alone
    • > 60% recurrence
  • The median time to recurrence
    • RT —> 125 months
    • No RT —> 66 months

Radiosurgery

EORTC 26021-22021 is an important phase III trial
Will randomize patients following subtotal resection or biopsy.

  • Observation
  • Conformal external-beam radiotherapy
  • Radiosurgery

Chemotherapy has not been useful.Given the high estrogen and progesterone receptor expression on meningiomas, progesterone receptor antagonists have been tested but have not been found beneficial.

Grade II and III Meningioma

  • Atypical or malignant meningiomas, the recurrence rate after surgery( even complete resection) is high (41% to 100% at 5 years)
  • Postoperative RT after maximal resection is recommended for all patients
    • Will improve local control and survival.
  • Target volume is more generous
  • GTV is typically expanded by 1.5 to 2 cm around the contrast-enhancing visible tumor
  • Dose —> 60 Gy / 30 - 33 fractions
  • Systemic therapy has no defined role.
    • Vincristine, adriamycin, and cyclophosphamide (?)

Unresectable or Recurrent Meningioma

  • If surgery is not an option —> RT
  • Doxorubicin and dacarbazine or ifosfamide and mesna (?)
  • Low-dose daily hydroxyurea may have some activity (?)
  • Hormonal manipulation, including tamoxifen and the antiprogesterone drug RU486
    • Some activity in a SWOG phase II evaluation of tamoxifen in unresectable or refractory meningiomas. Partial response or prolonged tumor stabilization was seen in 47% of patients. However, a subsequent SWOG phase III, double-blind, randomized, placebo-controlled study of mifepristone for the treatment of unresectable meningioma was negative. Median freedom from progression was 10 months for mifepristone and 12 months for placebo.

Evidence-Based Treatment Summary

  • Small asymptomatic meningiomas in noncritical locations, especially in the elderly or in patients with other comorbidities can be observed.
  • The goal of surgery is to completely resect the meningioma, with negative margins as patients with WHO grades I and II completely resected meningiomas have low rates of relapse and can be observed postoperatively.
  • For subtotally resected or unresectable progressive meningioma radiotherapy is frequently used but has not been tested in a prospective clinical trial. Local control appears to be improved with postoperative radiotherapy. Both radiosurgery and radiotherapy have been used in this context, but have not been directly compared.
  • For high-grade and especially malignant meningioma postoperative radiotherapy is routinely recommended.
  • Primary radiotherapy or radiosurgery could be used for unresectable, progressive meningiomas.
  • Systemic therapy does not have a defined role in meningioma.