Meningiomas

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore

Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology

(Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA)

Meningioma

The Meningioma is a primary intracranial tumor that is one of the most common benign tumors within the cranium (head). About 40–60% of benign tumors are meningiomas. About 15% of all primary intracranial tumors (both benign and malignant) are meningiomas.

Origin: They originate from the arachnoid cap cells that occur most often at the arachnoid granulations, which are near the midline adjacent to the superior sagittal sinus (the large midline vein of the head). Another location is the tela choroidea in the ventricles. They are therefore intracranial but not intracerebral (within the head but not in the brain). In other words, they usually occur from the covering of the brain called the dura and not from within the brain.

Epidemiology and Characteristics

• Age: The peak age is from 40 to 60 years.

• Sex: It is more common in females than males.

• Genetics: 72% of tumors have monosomy 22.

• Risk factors: Previous radiation, neurofibromatosis type 2 (NF2).

• Locations:

  • Cranial (within the head): 90%

  • Spinal canal: 9%

  • Others (neck, parotid, etc.): 1%

  • About 50% are parasagittal and convexity (near the midline and over the lobes of the brain).

• Grading: WHO classification I, II, III – from the least to the most aggressive.

• Pathology: Meningothelial, fibroblastic, psammomatous, angiomatous, and transitional (most common).

• Aggressive variants: They invade the brain, have necrosis, mitosis, papillary features, or are locally recurrent.

• Malignant: As above, with metastases.

  
  

Clinical Features

They may be symptomatic or asymptomatic at the time of discovery.Usual symptoms may include:

• Headaches

• Seizures

• Loss of any of the senses (smell, taste, hearing, vision, sensation)

• Motor weakness (hemiparesis)

• Memory loss

• Language problems (dysphasia, aphasia)

  
  

Some people with these tumors are mistakenly diagnosed with dementia, strokes, or psychiatric problems.

Diagnostic Tests

This includes a thorough neurological examination followed by brain scanning.

• In emergencies, a CT of the brain with contrast can be done quickly.

• An MRI of the brain with gadolinium is the definitive test.

The appearance of a meningioma on these tests is usually unique or characteristic enough for an accurate diagnosis most of the time.There are exceptions where a biopsy with tissue examination is still needed.

Biopsy

A biopsy is not mandatory for the diagnosis of a meningioma.

MRI with gadolinium and CT of the brain can be fairly clear in determining the diagnosis of a meningioma.The presence of an intracranial but extracerebral enhancing tumor with a dural tail is a classical finding.

A biopsy can be done by:

• Stereotactic computer-aided biopsy, where a needle is guided to the tumor after detailed computer planning based on pre-surgical imaging and using a stereotactic frame.

• Frameless stereotaxis, using a system like the StealthStation or Robotic Guidance.

  
  

Surgery

Microsurgery using a high-definition microscope and microinstruments is the latest type of surgery for meningiomas.CAN/CAM (Computer Aided Neurosurgery / Computer Aided Microsurgery) and VR technology can also be used.Lasers, “Super-Lasers”, CUSAs / Ultrasonic beams, the Malis technique can be used for tumor removal.The StealthStation and other neuro-navigation systems are useful in allowing a minimally invasive approach in the removal of these tumors.

Radiosurgery

Radiosurgery refers to computer-planned, accurately focused high energy beams used for non-invasive tumor treatment. Radiosurgery has been shown to be effective for meningiomas.Modern systems include:

• Gamma Knife

• Novalis systems with Photon Beams

• Proton Beam

  
  

Treatment methods:

• Single session

• Multiple sessions: Known as SRT (stereotactic radiation therapy) or FSR (fractionated stereotactic radiosurgery)

  
  

New forms include MicroRadiosurgery and Proton Beam Therapy.

Combined Treatment

Combined Microsurgery and Radiosurgery (CMR) uses both modalities for treating large, difficult-to-remove, or dangerously located meningiomas.This can be a lower risk protocol for complete tumor removal, especially in higher risk patients.

Recent Advances

Molecular Profiling

Molecular profiling has revolutionised meningioma diagnosis and classification. The 2021 WHO classification now incorporates molecular features alongside histological grading.

Key molecular alterations include:

• NF2 mutations: Found in ~60% of sporadic meningiomas

• TRAF7, KLF4, AKT1, SMO mutations: Common in non-NF2 mutated meningiomas

• SMARCE1 mutations: Associated with clear cell meningiomas

• BAP1, SMARCB1 mutations: Linked to high-grade meningiomas

  
  

DNA methylation profiling helps identify clinically relevant subgroups beyond traditional histological grading.

Neuroimaging

Recent imaging advances include:

• Arterial spin labelling and dynamic susceptibility contrast-enhanced MRI: Assess tumor vascularity and guide preoperative embolisation.

• MR spectroscopy and PET-MRI: Help distinguish meningiomas from malignant mimics.

• Perfusion imaging: Provides insight into tumor grade and recurrence potential.

• Machine learning algorithms: Predict tumor consistency and behaviour based on imaging features.

  
  

Treatment Advances

Surgical Approaches

• Minimally invasive techniques

  Endoscopic and keyhole approaches reduce morbidity and improve cosmetic results.

  
  

• Intraoperative imaging and navigation

  Enhance resection while preserving critical structures.

  
  

• Fluorescence-guided surgery

  Techniques like 5-ALA fluorescence help visualise tumour margins.

  
  

Radiation Therapy

• Stereotactic radiosurgery (SRS)

  Increasingly used for small to medium-sized tumors, especially near eloquent areas.

  
  

• Fractionated stereotactic radiotherapy (FSRT)

  Offers precision for larger tumors or those near critical structures.

  
  

• Proton beam therapy

  Reduces radiation exposure to surrounding healthy tissue.

  
  

Systemic Therapies

Although systemic therapies have shown limited historical efficacy, new developments include:

• Targeted therapies

  Inhibitors of molecular pathways (e.g., mTOR, VEGF, SMO) are in trials.

  
  

• Immunotherapy

  Checkpoint inhibitors and immunomodulatory treatments under investigation, especially for high-grade meningiomas.

  
  

Peptide Receptor Radionuclide Therapy (PRRT)

PRRT is emerging as a treatment for refractory meningiomas:

• A Phase II trial using 177LD showed 78% of patients were progression-free at 6 months.

• It targets somatostatin receptors, highly expressed in meningiomas.

  
  

Personalised Meningioma Therapy

The integration of molecular profiling and imaging supports personalised treatment strategies:

• Risk stratification

  Molecular features help identify high-risk patients and guide adjuvant therapy.

  
  

• Treatment selection

  Some molecular subtypes may respond differently to therapies.

  
  

Latest Research

Research areas showing promise:

• Liquid biopsy techniques

  Non-invasive methods for tumor characterization and monitoring are under investigation.

  
  

• Novel targeted therapies

  targeting specific molecular alterations (e.g., NF2 pathway inhibitors) are in development.

  
  

• Artificial intelligence

  Machine learning algorithms may enhance diagnosis, treatment planning, and outcome prediction.

  
  

Conclusions

The field of meningioma diagnosis and treatment is rapidly evolving. Molecular profiling and advanced imaging techniques are refining our ability to classify and prognosticate these tumors. While surgery and radiation therapy remain the mainstays of treatment, emerging targeted therapies and innovative approaches like PRRT offer new options for patients with refractory disease. As our understanding of meningioma biology deepens, the path towards truly personalized treatment strategies becomes clearer, holding the promise of improved outcomes for patients with these challenging tumors.