Residency · Residency · Neurosurgery
Meningiomas: Grading, Resection, and Recurrence
Overview
Meningiomas are the most common primary intracranial tumor, accounting for approximately 37% of all CNS tumors. They arise from arachnoid cap cells of the meninges and are typically benign, slow-growing, and extra-axial. Most are WHO grade 1 and curable with complete surgical resection. However, atypical (grade 2) and malignant (grade 3) meningiomas carry significant recurrence risk and require adjuvant therapy. Skull base meningiomas present unique surgical challenges due to their proximity to critical neurovascular structures.
Epidemiology
Meningiomas are the most common primary intracranial tumor in adults, with incidence increasing with age and peaking in the 6th to 7th decade. There is a female predominance of 2-3:1 for grade 1 tumors, though this is less pronounced for higher grades. The incidence in Black populations is approximately twice that of White populations. Risk factors include prior ionizing radiation, NF2 (which causes bilateral meningiomas), and hormonal influence as evidenced by progesterone receptor expression. Incidental meningiomas are found on 1-2% of brain MRIs.
WHO 2021 Classification and Grading
Grade 1 (Benign) -- ~80%
Grade 1 meningiomas encompass numerous histologic subtypes including meningothelial, fibrous, transitional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, and metaplastic variants. They carry a low recurrence rate of 7-20% at 10-20 years.
Grade 2 (Atypical) -- ~15-18%
Atypical meningiomas are defined by any one of the following: 4-19 mitoses per 10 high-power fields, brain invasion, or the presence of three or more of five morphologic criteria (sheeting, macronucleoli, small cell change, hypercellularity, and spontaneous necrosis). The clear cell and choroid subtypes are automatically classified as grade 2. The recurrence rate is 30-40% at 5 years.
Grade 3 (Malignant) -- ~2-3%
Malignant meningiomas are defined by 20 or more mitoses per 10 high-power fields, or frank anaplasia resembling carcinoma, sarcoma, or melanoma. The papillary and rhabdoid subtypes are automatically grade 3. The recurrence rate reaches 50-80% at 5 years, and extracranial metastasis can occur, though this is rare.
| WHO Grade | Frequency | Criteria | Recurrence (5-10 yr) | Auto-Grade Subtypes |
|---|---|---|---|---|
| 1 (Benign) | ~80% | Low mitotic rate, no invasion | 7-20% (10-20 yr) | Meningothelial, fibrous, transitional, psammomatous |
| 2 (Atypical) | ~15-18% | 4-19 mitoses/10 HPF, brain invasion, or ≥3 morphologic criteria | 30-40% (5 yr) | Clear cell, choroid |
| 3 (Malignant) | ~2-3% | ≥20 mitoses/10 HPF, frank anaplasia, or TERT/CDKN2A/B | 50-80% (5 yr) | Papillary, rhabdoid |
Molecular Markers (WHO 2021)
TERT promoter mutation or homozygous CDKN2A/B deletion upgrades any meningioma to grade 3 regardless of histology. NF2/Merlin loss is the most common genetic alteration and is associated with fibrous and transitional subtypes. Non-NF2 mutations including AKT1, SMO, PIK3CA, KLF4, and TRAF7 are associated with specific skull base locations and subtypes; for example, secretory meningiomas characteristically harbor KLF4 and TRAF7 mutations. DNA methylation profiling is increasingly used for prognostication independent of WHO grade.
Clinical Presentation
Many meningiomas are asymptomatic and discovered incidentally. Seizures are the most common presenting symptom for convexity meningiomas. Headache from dural stretching or raised intracranial pressure may occur. Focal deficits depend on location. Visual changes can result from optic nerve compression in tuberculum sellae or clinoid meningiomas, or from visual field cuts with parafalcine or occipital tumors. Proptosis or diplopia is seen with sphenoid wing meningiomas. Hyperostosis may present as palpable skull thickening overlying en plaque meningiomas.
Location-Specific Presentations
Parasagittal and falcine meningiomas produce leg weakness and seizures, with the risk of sagittal sinus involvement. Convexity meningiomas cause focal deficits corresponding to the underlying cortex. Sphenoid wing meningiomas present differently depending on location: medial (clinoidal) tumors cause visual loss and may involve the cavernous sinus, while lateral tumors produce temporal lobe mass effect. Olfactory groove meningiomas cause anosmia and personality changes, and may produce Foster Kennedy syndrome. Tuberculum sellae meningiomas compress the optic nerve or chiasm, causing visual loss. CPA meningiomas produce hearing loss, facial weakness, or trigeminal neuralgia. Foramen magnum meningiomas cause suboccipital pain, myelopathy, and lower cranial nerve palsies. Petroclival meningiomas produce multiple cranial neuropathies and brainstem compression.
<image> Sagittal and axial MRI (T1 post-gadolinium) showing a large homogeneously enhancing parasagittal meningioma with a broad dural base, dural tail sign, and compression of the underlying motor cortex. The adjacent CT bone window shows hyperostosis of the overlying calvarium. Key diagnostic features are annotated including the extra-axial location, CSF cleft sign, and dural tail. Radiological teaching illustration. </image>
Imaging
On MRI with gadolinium, meningiomas appear as homogeneous, intensely enhancing, dural-based masses with the characteristic dural tail sign. On T2-weighted imaging they are iso- to slightly hyperintense, though calcified meningiomas may be hypointense. The CSF cleft sign (a thin CSF rim between tumor and brain) confirms the extra-axial location. MR venography or CTA is essential for parasagittal and falcine meningiomas to assess sinus involvement and patency. CT identifies calcification and hyperostosis. MR perfusion typically shows high rCBV reflecting the dural blood supply. DSA or angiography may be considered for preoperative embolization of large or vascular meningiomas and identifies feeding vessels, with the middle meningeal artery being the most common.
Surgical Management
Simpson Grading of Resection
The Simpson grading system describes the completeness of meningioma resection. Grade I is complete resection including involved dura and abnormal bone, with a recurrence rate of approximately 9%. Grade II is complete resection with coagulation of the dural attachment, carrying a 19% recurrence rate. Grade III is complete resection without dural treatment or extradural extension, at 29% recurrence. Grade IV is subtotal resection, with 44% recurrence. Grade V is decompression or biopsy only. The Simpson grade remains prognostically significant, though its relevance has been debated in the era of modern microsurgery and adjuvant radiotherapy.
| Simpson Grade | Definition | Recurrence Rate |
|---|---|---|
| I | Complete resection + involved dura + abnormal bone | ~9% |
| II | Complete resection + coagulation of dural attachment | ~19% |
| III | Complete resection without dural treatment | ~29% |
| IV | Subtotal resection | ~44% |
| V | Decompression or biopsy only | N/A |
Observation
Observation is appropriate for small, asymptomatic, incidental meningiomas. Serial MRI is performed every 6-12 months initially, then annually if the tumor remains stable. The mean growth rate of untreated meningiomas is approximately 2-4 mm per year, though many remain stable for years. Calcified meningiomas are less likely to grow. Intervention is considered if the tumor becomes symptomatic, grows more than 2-3 mm per year, or develops surrounding edema.
Preoperative Embolization
Preoperative embolization should be considered for large, hypervascular tumors to reduce intraoperative blood loss. Middle meningeal artery feeders are the most amenable to embolization. The procedure is performed 24-72 hours before surgery. There is a risk of cranial nerve injury with embolization of skull base tumors.
Surgical Considerations by Location
Convexity meningiomas are the most straightforward, allowing en bloc resection with involved dura and bone. Parasagittal and falcine meningiomas require assessment of sagittal sinus involvement with MRV; a completely occluded sinus can be resected, but a patent sinus in the posterior third should never be sacrificed due to the risk of venous infarction. Medial sphenoid wing (clinoidal) meningiomas may require anterior clinoidectomy, and ICA encasement limits complete resection. Olfactory groove meningiomas are approached via bifrontal craniotomy or expanded endonasal approach, with attention to preserving the anterior cerebral arteries and reconstructing the anterior skull base floor. Tuberculum sellae meningiomas can be accessed via transcranial or endoscopic endonasal approaches, preserving the visual apparatus and pituitary stalk. CPA meningiomas are approached via the retrosigmoid route, preserving cranial nerves VII, VIII, and the lower cranial nerves. Petroclival meningiomas are among the most challenging intracranial tumors; staged approaches may be required, and subtotal resection should be accepted to preserve the brainstem and cranial nerves. Foramen magnum meningiomas are accessed via the far-lateral approach, respecting the vertebral artery, with C1 laminectomy often needed.
<image> Illustration showing the Simpson grading system for meningioma resection. Grade I shows complete tumor removal with excision of dural attachment and abnormal bone. Grade II shows complete removal with coagulation (bipolar) of the dural attachment. Grade III shows complete removal without dural treatment. Grade IV shows subtotal resection with residual tumor. Each grade is shown as a cross-sectional diagram of the meningioma at its dural base with corresponding surgical completeness. Recurrence rates are listed beside each grade. </image>
Adjuvant Therapy
Radiation Therapy for Atypical/Malignant Meningiomas
For grade 2 meningiomas with subtotal resection, adjuvant radiation therapy is recommended at 54-60 Gy in 30-33 fractions. Whether to administer adjuvant RT after gross total resection of grade 2 meningiomas remains debated, with the ROAM/EORTC 1308 trial evaluating this question. Grade 3 meningiomas warrant adjuvant RT regardless of extent of resection, at doses of 59.4-60 Gy. Proton beam therapy is potentially advantageous for skull base meningiomas due to its dose conformality.
Stereotactic Radiosurgery
SRS achieves excellent local control for small (under 3 cm) WHO grade 1 meningiomas, reaching 90-95% at 10 years. It can be used as primary treatment for surgically inaccessible lesions, most notably cavernous sinus meningiomas, where SRS achieves greater than 95% tumor control and is often preferred over surgery. The typical marginal dose is 12-14 Gy.
Systemic Therapy
No standard chemotherapy has proven efficacy for meningiomas. Somatostatin receptor agonists such as octreotide have limited efficacy. Bevacizumab has some evidence supporting its use in recurrent or progressive meningiomas. Clinical trials are investigating targeted therapies including CDK4/6 inhibitors, mTOR inhibitors, and PD-1 inhibitors based on molecular profiling.
Recurrence Management
Recurrent meningiomas may be managed by re-resection if surgically feasible, SRS for small recurrences, fractionated RT for larger or diffuse dural recurrences, and combination approaches for aggressive histologies. Clinical trials are an option for refractory disease.
<image> Axial MRI (T1 post-gadolinium) series showing common meningioma locations: convexity (with broad dural base), parasagittal (abutting the superior sagittal sinus), sphenoid wing (medial, encasing the ICA), olfactory groove (bilateral frontal), and CPA (displacing the brainstem). Each location is labeled with key surgical considerations and relevant neurovascular structures at risk. Multi-panel radiological teaching illustration. </image>
Clinical Pearls
A patent posterior third of the superior sagittal sinus must never be sacrificed, as venous infarction of both hemispheres would be catastrophic; residual tumor on the sinus should be left and treated with SRS. Cavernous sinus meningiomas are often best managed with SRS rather than aggressive surgery, given the high cranial nerve morbidity of surgical resection. TERT promoter mutation or CDKN2A/B homozygous deletion upgrades any meningioma to grade 3 regardless of mitotic count or histologic appearance, so molecular markers should always be checked. Secretory meningiomas (KLF4/TRAF7-mutant) cause disproportionate peritumoral edema relative to their size, which resolves after resection. En plaque meningiomas infiltrate the dura diffusely and may involve bone extensively, making complete resection often impossible. Radiation-induced meningiomas are more likely to be atypical or malignant, multifocal, and occur at a younger age. Peritumoral edema on preoperative imaging does not equate to brain invasion; it may represent venous congestion or secretory factors.
References
- Louis DN, et al. "The 2021 WHO Classification of Tumors of the Central Nervous System." Neuro-Oncology. 2021;23(8):1231-1251.
- Simpson D. "The Recurrence of Intracranial Meningiomas after Surgical Treatment." J Neurol Neurosurg Psychiatry. 1957;20(1):22-39.
- Goldbrunner R, et al. "EANO Guideline on the Diagnosis and Treatment of Meningiomas." Neuro-Oncology. 2021;23(11):1821-1834.
- Sahm F, et al. "DNA Methylation-Based Classification and Grading System for Meningioma." Acta Neuropathologica. 2017;134(6):935-949.
- Pollock BE, et al. "Stereotactic Radiosurgery for Cavernous Sinus Meningiomas." J Neurosurg. 2003;99(5):803-807.
