Meningioma
Dr. Prem Pillay, Singapore
Senior Neurosurgeon, Neurosurgical Oncologist and Meningioma Expert
(Higher Training in Meningiomas: Cleveland Clinic, USA and MD Andersons Cancer Center, USA)
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 archnoid 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 occur usually from the covering of the brain called the dura and not from within the brain.
| Age: | The peak age is from a 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 (NF 2). |
| Locations: | Cranial (within the head): 90%, spinal canal : 9% and others 1% (neck, parotid etc) About 50% are parasagittal and convexity (near the midline and over the lobes of the brain). |
| Grading: | WHO classification I,II,III from that least to the most aggressive. |
| Pathology: | Meningothelial, fibroblastic,psmmomatous, angiomatous, and transitional (most common). |
| Aggressive variants: | They invade brain, have necrosis, mitosis, papillary, or are locally recurrent. |
| Malignant: | As above with metastases. |
| Clinical Features: | They either be symptomatic or asymptomatic at the time of discovery. The 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 diagneosed with Dementia , strokes or psychiatric problems. |
| Diagnostic tests: | This includes a thorough neurological examination followed by brain scanning. In an emergency situation a CT of the brain with contrast can be done quickly, but an MRI of the brain with gadolinium is still the definitive test.
The appearance of a meningioma on these tests is usally 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 the technique of stereotactic computer aided biopsy where a needle is guided to the tumor after detailed computer planning is done based on pre-surgical imaging and using a stereotactic frame. There is also the technique of frameless stereotaxis using a system like the StealthStation or with 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), VR technology can also be used. Lasers,”Super-Lasers”,CUSAs/
Radiosurgery
Radiosurgery refers to computer planned, and accurately focused high energy beams that are used for non-invasive tumor treatment. Radiosurgery has been shown to be effective for the treatment of meningiomas. Modern systems in use include the Gamma-knife, Novalis type systems with Photon Beams and the Proton Beam. The two ways in which the treatments can be given are either in a single session or in multiple sessions. The latter is often referred to 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) is where both modalities are used for the treatment of large , difficult to remove, or dangerous location meningiomas. This can be a lower risk protocol for complete tumor removal especially in higher risk patients.
Recent Advances
Recent advances in the diagnosis and treatment of meningiomas have significantly improved our understanding and management of these common intracranial tumors. This summary will highlight key developments in molecular profiling, imaging techniques, surgical approaches, radiation therapy, and emerging targeted therapies for meningiomas.
Molecular Profiling
Molecular profiling has revolutionized meningioma diagnosis and classification. The 2021 World Health Organization (WHO) classification now incorporates molecular features alongside histological grading.
Key molecular alterations include:
- NF2 mutations: Found in approximately 60% of sporadic meningiomas
- TRAF7, KLF4, AKT1, and SMO mutations: Common in non-NF2 mutated meningiomas
- SMARCE1 mutations: Associated with clear cell meningiomas
- BAP1 and SMARCB1 mutations: Linked to high-grade meningiomas
DNA methylation profiling has emerged as a powerful tool for meningioma classification and prognostication. It can help identify clinically relevant subgroups beyond traditional histological grading.
Neuroimaging
Neuroimaging plays a crucial role in meningioma diagnosis and treatment planning. Recent advances include:
- Arterial spin labeling and dynamic susceptibility contrast-enhanced MRI: These techniques help assess tumor vascularity, informing decisions about preoperative embolization.
- MR spectroscopy and PET-MRI: Aids in distinguishing meningiomas from malignant mimics.
- Perfusion imaging: Provides insights into tumor grade and potential for recurrence.
- Machine learning algorithms: Emerging technologies show promise in predicting tumor consistency and behavior based on imaging features.
Treatment Advances
Surgical Approaches
Surgery remains the primary treatment for symptomatic meningiomas. Recent advances include:
- Minimally invasive techniques: Endoscopic and keyhole approaches for select tumors, reducing morbidity and improving cosmetic outcomes.
- Intraoperative imaging and navigation: Enhances the extent of resection while preserving critical structures.
- Fluorescence-guided surgery: Techniques like 5-ALA fluorescence help visualize tumor margins.
Radiation Therapy
Advances in radiation therapy have improved local control rates and reduced toxicity:
- Stereotactic radiosurgery (SRS): Increasingly used for small to medium-sized meningiomas, especially in eloquent locations.
- Fractionated stereotactic radiotherapy (FSRT): Offers precise treatment for larger tumors or those near critical structures.
- Proton beam therapy: Shows promise in reducing radiation exposure to surrounding healthy tissue.
Systemic Therapies
While systemic therapies have historically shown limited efficacy in meningiomas, recent developments offer new hope:
- Targeted therapies: Inhibitors targeting specific molecular pathways (e.g., mTOR, VEGF, SMO) are under investigation in clinical trials
- Immunotherapy: Checkpoint inhibitors and other immunomodulatory approaches are being explored, particularly for high-grade meningiomas.
Peptide Receptor Radionuclide Therapy (PRRT)
PRRT has emerged as a promising option for refractory meningiomas:
- A phase II trial using 177LD showed encouraging results, with 78% of patients progression-free at 6 months
- This approach leverages the high expression of somatostatin receptors in meningiomas to deliver targeted radiotherapy.
Personalised Meningioma Therapy
The integration of molecular profiling and advanced imaging has paved the way for more personalized treatment strategies:
- Risk stratification: Molecular features help identify patients at higher risk of recurrence or aggressive behavior, informing decisions about adjuvant therapy.
- Treatment selection: Emerging data suggest that certain molecular subtypes may respond differently to various treatment modalities.
Latest Research
Several areas of ongoing research hold promise for further improving meningioma management:
- 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.
