Meningioma

Executive Summary

A meningioma is a primary central nervous system (CNS) tumor arising from the meninges—the membranous layers surrounding the brain and spinal cord. Specifically, these tumors originate from arachnoid cap cells (arachnoid granulations) of the arachnoid mater. Meningiomas represent the most common primary intracranial tumor in adults, accounting for approximately 37–40% of all primary CNS tumors. While the vast majority (80–90%) are classified as World Health Organization (WHO) Grade 1 (benign), their location within the rigid confines of the skull or spinal canal can cause significant neurological morbidity due to mass effect, vascular encasement, or cranial nerve compression. This article provides a detailed, patient-centered, and clinically rigorous overview of meningioma pathophysiology, classification, clinical presentation, diagnostic workup, management strategies, and long-term surveillance.

1. Epidemiology and Risk Factors

Incidence and Demographics

• Incidence: Approximately 8–9 cases per 100,000 person-years in the United States.
• Age: Peak incidence occurs in the sixth and seventh decades of life. They are rare in children (< 2% of cases).
• Sex: A marked female predominance exists (Female:Male ratio ~ 2:1 to 3:1 for intracranial tumors; ~ 4:1 for spinal meningiomas). This disparity suggests a hormonal influence.
• Race/Ethnicity: Higher incidence rates are reported in Black/African American populations compared to White populations in the US.

Established Risk Factors

2. Pathophysiology and Molecular Biology

Cellular Origin

Meningiomas arise from arachnoid cap cells (specialized arachnoid granulation cells) located predominantly near dural venous sinuses, the skull base, and the spinal cord. These cells possess both mesenchymal and epithelial characteristics, explaining the diverse histological patterns observed.

Key Molecular Drivers

Understanding molecular pathogenesis is critical for the new WHO CNS5 (2021) Classification, which integrates histology with molecular markers.

1. NF2 Gene Inactivation (Chromosome 22q loss): The most common genetic event (~50–60% of sporadic cases). Loss of Merlin function disrupts contact inhibition and Hippo signaling pathway regulation (YAP/TAZ activation).
2. Non-NF2 Mutations (Mutually exclusive with NF2 loss):

• TRAF7: ~25% (often secretory/grade 1).
• KLF4: ~10% (often secretory/grade 1).
• AKT1 (E17K): ~7–15% (often meningothelial/transitional).
• SMO: ~5% (often basal/grade 1; targetable by vismodegib).
• PIK3CA: ~5–10%.
• POLR2A: ~6%.

1. Aggressive/High-Grade Drivers:

• TERT Promoter Mutations: Strongly associated with shorter progression-free survival and higher grades (Grade 2/3).
• CDKN2A/B Homozygous Deletion: Diagnostic criterion for WHO Grade 3 (Anaplastic) regardless of mitotic count.
• H3K27me3 Loss: Epigenetic silencing (via EZHIP or KDM6A/B mutations) defines a subset of aggressive posterior fossa meningiomas.

WHO CNS5 Classification (2021) – Grading System

The current classification moves beyond pure histology to an Integrated Diagnosis (Histology + Grade + Molecular Features).

Clinical Pearl:** Brain invasion is defined as tumor cells infiltrating brain parenchyma beyond the Virchow-Robin space. It upgrades a histologically bland tumor to Grade 2. TERT promoter mutations upgrade a Grade 1 histology to Grade 2 molecularly.

Histological Subtypes (WHO CNS5)

There are 15 recognized histological subtypes. The most common include:

• Meningothelial (Syncytial): Whorls, psammoma bodies (calcified concentric laminations). Most common (~60%).
• Fibrous (Fibroblastic): Spindle cells, collagen bundles, “parallel arrays.”
• Transitional (Mixed): Features of both meningothelial and fibrous.
• Psammomatous: Abundant psammoma bodies.
• Angiomatous: Prominent vascular component (high bleed risk).
• Secretory: Glandular lumina, PAS-positive secretions, TRAF7/KLF4 mutations.
• Clear Cell / Chordoid: Automatically Grade 2. Clear cytoplasm / myxoid matrix with chordoid architecture.
• Rhabdoid / Papillary: Automatically Grade 3. Rhabdoid: eccentric nuclei, eosinophilic inclusions. Papillary: papillary architecture, high mitotic rate.

3. How Does It Look? (Radiological & Gross Pathology)

This section details the visual appearance of meningiomas across imaging modalities and intraoperative findings, crucial for diagnosis and surgical planning.

Neuroimaging: The “Meningioma Look” on MRI

MRI with Gadolinium-based contrast is the gold standard. CT is adjunctive for bone/calcification assessment.

Classic “Textbook” Features (Grade 1, Convexity/Parasagittal)

Advanced Imaging Signs

• CSF Cleft Sign (T2): A thin dark line between tumor and brain = Good surgical plane.
• Brain Invasion (Grade 2 criteria): Irregular, “fingering” infiltration into parenchyma on post-contrast T1/FLAIR; loss of CSF cleft.
• Peritumoral Edema (FLAIR/T2): Vasogenic edema (“T2 flare”). Extent correlates with size, venous obstruction, secretory subtype, and higher grade. Can mimic glioma.
• Hyperostosis (CT Bone Window): Thickening/sclerosis of adjacent skull base bone (reactive osteoblastic activity vs. direct tumor invasion). Common in sphenoid wing/planum sphenoidale tumors.
• Lytic Destruction (CT): Bone destruction suggests higher grade (Grade 2/3) or rare “bone-invasive” Grade 1 variant.
• En Plaque Morphology: Sheet-like dural thickening (< 2cm thick) rather than a discrete mass. Common in sphenoid wing, olfactory groove, spinal. Higher recurrence risk due to incomplete resection.

CT Scan Findings

• Calcifications (Psammoma Bodies): Seen in 20–30% on non-contrast CT. “Popcorn” or punctate.
• Hyperostosis: Best visualized on CT bone algorithm.
• Acute Hemorrhage: Hyperdense on non-contrast CT (rare presentation: apoplexy).

Angiography (DSA / CTA / MRA)

• Supply: Predominantly External Carotid Artery (ECA) branches (Middle Meningeal Artery, Accessory Meningeal, Ascending Pharyngeal, Lacrimal, Ethmoidal arteries).
• Venous Drainage: Critical for surgical planning. Tumor drains into Dural Venous Sinuses (Sagittal, Transverse, Cavernous). Sinus Invasion/Occlusion assessed via MR Venography (MRV) or DSA.
• Tumor Blush: Dense, persistent capillary blush in capillary/venous phase.
• Pre-op Embolization: Used for large, vascular (angiomatous), skull base tumors to reduce intraoperative blood loss (typically 24–48 hrs pre-op).

Intraoperative / Gross Pathology Appearance

• Consistency: Ranges from soft, friable, vascular (angioblastic, secretory, high T2 signal) to firm, rubbery, tough, gritty (fibrous, psammomatous, low T2 signal, calcified).
• Color: Grey-pink to reddish (vascular). Yellowish if xanthomatous/cholesterol deposits.
• Surface: Smooth, lobulated, often capped by compressed arachnoid/brain.
• Attachment: Broad-based on dura. Simpson Grade of resection depends on visualization and removal of this dural attachment + involved bone.
• Cystic Components: Seen in secretory or microcystic subtypes; fluid often xanthochromic (high protein).

4. Clinical Presentation: Symptoms

Symptoms are dictated almost entirely by tumor location (compression of specific neural structures), size (mass effect/edema), and growth rate. Many small meningiomas are incidental findings (asymptomatic).

General Mechanisms of Symptom Generation

1. Mass Effect / Compression: Direct pressure on brain, cranial nerves, spinal cord.
2. Peritumoral Edema: Vasogenic edema expands the “functional lesion volume” far beyond tumor margins.
3. Vascular Compromise: Venous sinus occlusion → venous infarction/edema; Arterial encasement/narrowing → ischemia.
4. Seizure Focus: Cortical irritation by tumor/edema/hemosiderin (from microbleeds).
5. Hormonal/Secretory Effects: Rare paraneoplastic syndromes (e.g., hypertrophic osteoarthropathy, hypoglycemia).

Symptoms by Anatomical Location (The “Clinical Anatomy” Approach)

A. Supratentorial Convexity & Parasagittal (Frontal/Parietal) ~ 35–40%

• Seizures: Most common presenting symptom (30–50%). Focal onset (motor/sensory) ± secondary generalization.
• Focal Neurological Deficits:
• Frontal: Personality change, executive dysfunction, apathy, gait apraxia, Broca’s aphasia (dominant), grasp reflex.
• Parietal: Sensory loss, neglect syndrome (non-dominant), Gerstmann syndrome (dominant: acalculia, agraphia, finger agnosia, L-R confusion), visual field defects (inferior quadrantanopia).
• Headache: Non-specific, tension-type or migraine-like; worse with Valsalva if large.
• Parasagittal Specifics: Bilateral leg weakness (paraparesis) if bilateral compression of motor cortex; venous infarction risk if Superior Sagittal Sinus (SSS) occluded.

B. Skull Base (Complex Surgery, Cranial Nerve Signs Dominant)

C. Spinal Meningiomas (~12% of all meningiomas)

• Location: Thoracic > Cervical > Lumbar. Ventral/Lateral to cord (dorsal rare).
• Sex: Strong female predominance (Peak 40–60 yrs).
• Symptoms (Progressive Myelopathy/Radiculopathy):

1. Local Pain: Radicular (dermatomal) or axial back pain (worst at night/lying flat – venous engorgement).
2. Myelopathy: Spastic weakness, sensory level, hyperreflexia, Babinski sign, bowel/bladder dysfunction (urgency/retention).
3. Brown-Séquard Syndrome: Ipsilateral motor loss/proprioception loss + Contralateral pain/temp loss (lateral compression).
4. Radiculopathy: Focal weakness/wasting (e.g., hand intrinsic wasting in C7-T1 tumors).

D. Intraventricular Meningiomas (Rare, < 2%)

• Origin: Choroid plexus, tela choroidea, septum pellucidum.
• Symptoms: Obstructive Hydrocephalus (Headache, nausea, vomiting, papilledema, cognitive decline). Seizures. Focal deficits rare unless huge.

E. Atypical / Anaplastic (Grade 2/3) Specifics

• Rapid Progression: Weeks to months (vs. years for Grade 1).
• Severe Edema: Disproportionate to tumor size.
• Invasion: Brain invasion (seizures, fixed deficits), Bone destruction (palpable skull mass), Scalp invasion.
• Metastasis (Grade 3): Lung, Liver, Bone, Lymph nodes (rare but definitive malignancy).

Symptom Onset Timeline & Red Flags

• Indolent: Years of subtle personality change, mild headache, gradual visual loss.
• Acute/Subacute: Seizure (new onset in adult = image brain), Apoplexy (intratumoral hemorrhage – sudden headache, deficit), Venous Infarction (sinus thrombosis).
• Red Flags for Higher Grade: Rapidly worsening deficit, intractable seizures, significant peritumoral edema disproportionate to size, bone destruction on CT, young patient (< 40) with large tumor.

5. Diagnostic Workup

Standard Diagnostic Algorithm

1. History & Neurological Exam: Cranial nerves, motor/sensory, reflexes, gait, cognition, visual fields (formal perimetry), fundoscopy (papilledema/optic atrophy).
2. MRI Brain/Spine with Contrast: Protocol: Pre/post T1, T2, FLAIR, DWI/ADC, SWI/GRE (microbleeds/calcification), MR Venography (MRV). MR Spectroscopy (MRS): Elevated Alanine peak (1.4 ppm) + Glutamine/Glutamate; Absent NAA (neuronal loss); Helps differentiate from glioma (high Cho/NAA) or metastasis.
3. CT Head (Bone Window): If hyperostosis suspected or preoperative navigation registration.
4. CTA / MRA / DSA: If vascular encasement suspected, pre-embolization planning, or differential includes vascular malformation.
5. Endocrine Workup: Prolactin, IGF-1, Cortisol, TSH, FSH/LH, Testosterone/Estradiol (if sellar/parasellar).
6. Neuropsychological Testing: Baseline cognitive function (especially frontal tumors).
7. Genetic Counseling/Testing: If NF2 features (bilateral VS, young age, multiple meningiomas, family history) or syndromic features.

Differential Diagnosis (Imaging-Based)

6. Management Strategies

Management is multidisciplinary (Neurosurgery, Neuro-oncology, Radiation Oncology, Neuroradiology, Endocrinology, Ophthalmology, Rehabilitation). Decision making balances tumor control vs. neurological preservation (Quality of Life).

Observation (“Watch and Wait”) / Active Surveillance

Indications:

• Asymptomatic, incidental, small (< 2.5–3 cm), no significant mass effect/edema.
• Elderly / Comorbid patients (high surgical/anesthesia risk).
• Slow growth documented on serial imaging.
• Patient preference.

Protocol:

• MRI Brain at 3–6 months post-diagnosis (establish growth rate).
• Then every 6–12 months for 2–3 years.
• Then annually indefinitely (meningiomas grow lifelong).
• Growth Threshold for Intervention: > 2–3 mm/year radial growth OR development of symptoms/edema/sinus occlusion.

Surgical Resection: The Primary Curative Modality

Goal: Maximal Safe Resection (Gross Total Resection – GTR) with neurological preservation.

Simpson Grading Scale (Extent of Resection) – Still the Prognostic Standard

Modern Nuance: Simpson Grade 0 (Macroscopic + Microscopic/Endoscopic clearance of dural margin) is increasingly sought for convexity tumors. For skull base, Simpson Grade II (or “Near Total”) is often the maximal safe goal** to preserve cranial nerves/vasculature. STR + Radiation = equivalent control to GTR for many locations.

Surgical Approaches (Tailored to Location)

• Convexity/Parasagittal: Craniotomy over tumor. Sagittal Sinus Management: If sinus occluded → resect invaded sinus wall. If patent → preserve sinus (reconstruction or lateral wall preservation).
• Olfactory Groove / Planum: Endoscopic Endonasal Approach (EEA) vs. Bifrontal Craniotomy. EEA preferred for midline, vascular encasement < 180 degrees; Craniotomy for large lateral extension, optic nerve decompression, or olfactory preservation.
• Tuberculum Sellae: EEA (Standard for most). Excellent visual decompression.
• Sphenoid Wing: Pterional / Orbitozygomatic Craniotomy. Drilling sphenoid ridge (hyperostosis). Optic nerve decompression (optic canal unroofing).
• Cavernous Sinus / Petroclival: Subtotal Resection (STR) + Radiosurgery is standard. Radical resection carries unacceptable CN deficit risk. “Debulk and Radiate.”
• Posterior Fossa (CPA/FM): Retrosigmoid / Far-Lateral / Transcondylar. Hearing preservation (CPA) / Brainstem decompression (FM). Neurophysiological monitoring (BAEP, CN VII, X, XI, MEPs/SSEPs) Mandatory.
• Spinal: Laminectomy / Laminoplasty. Ventral tumors require careful dissection off pia/arteries (anterior spinal artery syndrome risk). Intraoperative monitoring (MEPs/SSEPs) critical.

Adjuncts

• Pre-op Embolization: Large, vascular, skull base (MMA feeders). Reduces blood loss ~30–50%.
• Neuro-navigation / 5-ALA Fluorescence: 5-ALA (Gliolan) shows fluorescence in ~80% of meningiomas (esp. Grade 2/3), aids Simpson Grade I.
• Intraoperative Neurophysiology (IONM): MEPs, SSEPs, BAEP, Cranial Nerve EMG (CN VII, X, XI, XII). Standard of care for skull base/posterior fossa/spinal.

Radiation Therapy (RT)

A. Stereotactic Radiosurgery (SRS) / Stereotactic Radiotherapy (SRT)

• Modality: Gamma Knife, CyberKnife, Linac-based (VMAT).
• Indications:
• Residual/Recurrent tumor post-surgery (Standard adjuvant for Grade 2/3; Selective for Grade 1 STR).
• Primary treatment for small-medium (< 3 cm) skull base tumors (Cavernous sinus, Petroclival, CPA) where surgery risks high morbidity.
• Elderly/Unfit patients.
• Dose: 12–14 Gy to margin (single fraction SRS) for benign; 25–30 Gy / 5 fractions (SRT) for large/optic apparatus proximity.
• Control Rates: > 90–95% at 5–10 years for Grade 1.
• Risks: Radiation necrosis (1–5%), Cranial neuropathy (delayed, 2–5% at 5 yrs), Secondary malignancy (very rare, < 1% at 20 yrs), Edema flare (transient).

B. Fractionated External Beam Radiotherapy (EBRT / IMRT / Proton Therapy)

• Indications: Grade 2 (Atypical) & Grade 3 (Anaplastic) post-op (Adjuvant). Large tumors near optic chiasm/nerves (fractionation spares optics). Recurrent tumors post-SRS.
• Dose: Grade 2: 50–54 Gy / 1.8–2.0 Gy fractions. Grade 3: 60 Gy.
• Proton Therapy: Advantage for skull base (sharp dose fall-off, sparing brainstem/optic/temporal lobes).

Systemic Therapy (Medical Management)

No FDA-approved chemotherapy for meningioma. Role limited to Recurrent/Progressive Grade 2/3 after surgery + RT exhaustion or inoperable.

7. Prognosis, Recurrence, and Long-Term Surveillance

Prognostic Factors

1. WHO Grade: Single strongest predictor (Gr 1 vs 2 vs 3).
2. Extent of Resection (Simpson Grade): GTR (Gr I/II) vs STR.
3. Molecular Markers: TERT promoter mut, CDKN2A/B del, H3K27me3 loss → Worse PFS/OS independent of histology.
4. Location: Skull base (lower GTR rates) vs Convexity.
5. Age / Performance Status: KPS > 70 better.
6. Sex: Female sex slightly better survival (independent of grade).

Recurrence Patterns

• Grade 1: Local recurrence at dural attachment site (Simpson II/III/IV). Median time to recurrence: 7–10 years. Lifelong risk.
• Grade 2: Local + Distant (CSF dissemination rare but possible). Median TTR: 3–5 years.
• Grade 3: Local + High rate of CSF dissemination + Systemic mets. Median TTR: < 2 years.

Surveillance Protocol (Post-Treatment)

• Grade 1 (GTR Simpson I/II): MRI at 3 months post-op (baseline), then 6 months, then annually for 5 years, then every 1–2 years indefinitely.
• Grade 1 (STR) / Grade 2: MRI at 3 months, then every 6 months for 3–5 years, then annually.
• Grade 3: MRI every 3–4 months for 2–3 years, then every 6 months. Spine MRI annually (CSF dissemination risk).
• Imaging: Contrast-enhanced MRI Brain (Spine if indicated). Standardized measurement (RANO criteria for meningioma – bi-dimensional).

Quality of Life & Survivorship Issues

• Seizure Management: Prophylactic AEDs not recommended post-op unless seizure history. Treat clinical seizures (Levetiracetam/Lacosamide preferred – low interaction).
• Endocrine Dysfunction: Screen annually if sellar/parasellar/suprasellar radiation/surgery.
• Cognitive Rehabilitation: Frontal lobe syndrome, memory clinics.
• Visual Rehabilitation: Low vision aids, prism glasses (diplopia).
• Psychosocial: Anxiety (“scanxiety”), depression, return to work/driving regulations.

8. Special Populations & Clinical Scenarios

Meningioma in Pregnancy

• Growth Acceleration: Progesterone/Estrogen receptors + increased blood volume/angiogenesis → rapid growth (esp. 2nd/3rd trimester).
• Management:
• Asymptomatic/Small: Defer treatment. Serial clinical exams + MRI without Gadolinium (Gd contraindicated/caution in pregnancy). Monitor visual fields.
• Symptomatic/Visual threat: Surgery in 2nd Trimester (14–28 wks) safest for fetus/anesthesia. Steroids for edema.
• Delivery: Vaginal delivery preferred unless neurological deficit prevents pushing or massive tumor with herniation risk (C-section).
• Postpartum: Tumors often stabilize/shrink. Re-image at 3–6 months postpartum.

Pediatric Meningioma (< 18 yrs)

• Rare (< 2%). Higher proportion Grade 2/3 (~30–40%).
• Associations: NF2 (high index of suspicion), Prior Cranial Radiation (therapy-related).
• Aggressive biology: Higher Ki-67, more NF2 mutations, TRAF7 rare.
• Treatment: Maximal safe resection + RT for Grade 2/3 (avoid RT < 3 yrs if possible).

Radiation-Induced Meningioma (RIM)

• Latency: 10–50 years (peak 20–30 yrs).
• Features: Multiple (30%), Higher Grade (Atypical/Anaplastic ~15-20%), Aggressive, Dural-based at field edge.
• Screening: Childhood cancer survivors (COG Guidelines) → MRI Brain every 2–5 years starting 10 yrs post-RT.

Multiple Meningiomas

• Definition: ≥ 2 distinct dural-based enhancing lesions.
• Workup: NF2 Genetic Testing (Blood + Tumor). Rule out metastasis (systemic staging).
• Management: Treat symptomatic/largest first. SRS ideal for multiple small lesions. Avoid whole brain RT.

9. Patient Frequently Asked Questions (FAQ)

Q: “Is a meningioma cancer?”

A: Most (80-90%) are benign (WHO Grade 1) – they do not spread to other organs. However, because they grow inside the rigid skull, they can be life-threatening or disabling by compressing the brain. “Benign” refers to microscopic behavior, not clinical harmlessness. Grade 2 (Atypical) and Grade 3 (Anaplastic) are malignant cancers.

Q: “Do I need surgery immediately?”

A: Not usually. If the tumor is small, asymptomatic, and not causing swelling (edema) or compressing critical structures, active surveillance (serial MRIs) is the standard of care. Surgery carries risks (infection, stroke, cranial nerve injury, seizure) that may outweigh the risk of a slow-growing tumor.

Q: “Will I lose my hearing / vision / facial movement?”

A: This depends entirely on location. Tumors in the cerebellopontine angle threaten hearing/facial nerve. Sphenoid wing/planum tumors threaten vision. Cavernous sinus tumors threaten eye movement/facial sensation. Your surgeon will discuss specific risks for your tumor location. Modern monitoring (IONM) drastically reduces permanent injury rates.

Q: “Can it come back after surgery?”

A: Yes. Recurrence risk correlates with Simpson Grade of resection and WHO Grade.

• Grade 1, Simpson I (dura+bone removed): ~9% at 10 years.
• Grade 1, Simpson IV (debulking only): ~40% at 10 years.
• Grade 2/3: Higher recurrence rates, earlier timeframe. Radiation after surgery significantly lowers this risk.

Q: “Does radiation cause cancer?”

A: The risk of a radiation-induced malignancy (second cancer) after SRS/EBRT for meningioma is very low (< 1% at 20 years). This risk is weighed against the near-certainty of tumor regrowth causing neurological damage if untreated. Modern techniques (Protons, SRS) minimize dose to normal brain.

Q: “Are there pills to shrink it?”

A: Currently, no medication is FDA-approved to cure or consistently shrink meningiomas. Hormonal therapy (anti-progesterone like Mifepristone) has failed in trials. Bevacizumab (Avastin) can shrink some recurrent/aggressive tumors temporarily but is not curative. Clinical trials are the best avenue for medical therapy.

Q: “Can I fly / scuba dive / play contact sports?”

A: Flying: Safe (cabin pressurized). Scuba/Contact Sports: Generally discouraged if you have a craniotomy defect (bone flap not yet healed/replaced), a ventriculoperitoneal (VP) shunt, or significant mass effect/edema. Discuss with your neurosurgeon.

Q: “Should my family be screened?”

A: Generally no, unless you have Neurofibromatosis Type 2 (NF2) (multiple meningiomas, bilateral vestibular schwannomas, family history, onset < 30) or a known genetic syndrome. Sporadic meningiomas are not inherited.

10. Conclusion

Meningiomas are a heterogeneous group of meningeal neoplasms requiring a nuanced, location-specific, and molecularly-informed approach. While the majority are histologically benign (WHO Grade 1), their anatomical location dictates clinical morbidity. The paradigm has shifted from “maximal resection at all costs” to “maximal safe resection” guided by molecular grading (WHO CNS5) and functional preservation. For residual, recurrent, or surgically inaccessible tumors—particularly at the skull base—stereotactic radiosurgery offers excellent durable control with minimal toxicity. The integration of molecular markers (TERT, CDKN2A/B, H3K27me3) into routine practice refines prognostication and identifies candidates for adjuvant therapy or clinical trials targeting actionable mutations (SMO, AKT1, FAK). Long-term, multidisciplinary survivorship care addressing seizure control, endocrinopathy, neurocognitive function, and psychosocial well-being is paramount for this growing population of patients living with a chronic, manageable neurological condition.

References

Clinical Guidelines & Classification Systems

• Louis, D.N. et al. (2021) ‘The 2021 WHO Classification of Tumors of the Central Nervous System: a summary’, Neuro-Oncology, 23(8), pp. 1231–1251. doi: 10.1093/neuonc/noab106.
• NCCN Guidelines (2024) Central Nervous System Cancers, Version 2.2024. National Comprehensive Cancer Network. Available at: https://www.nccn.org (Accessed: [Current Date]).
• EANO Guidelines (2021) ‘Diagnosis and treatment of meningiomas’, Neuro-Oncology, 23(4), pp. 556–568. doi: 10.1093/neuonc/noaa242.
• Goldbrunner, R. et al. (2016) ‘EANO guidelines for the diagnosis and treatment of meningiomas’, The Lancet Oncology, 17(8), pp. e383–e391. doi: 10.1016/S1470-2045(16)30143-4.

Epidemiology & Risk Factors

• Ostrom, Q.T. et al. (2023) ‘CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2016–2020’, Neuro-Oncology, 25(12 Suppl 2), pp. iv1–iv99. doi: 10.1093/neuonc/noad149.
• Claus, E.B. et al. (2012) ‘Exposure to ionizing radiation and risk of meningioma’, Neurosurgery, 71(1), pp. 128–135. doi: 10.1227/NEU.0b013e318252c77a.
• Wiemels, J. et al. (2010) ‘Allergy and risk of glioma and meningioma’, Cancer Epidemiology, Biomarkers & Prevention, 19(5), pp. 1341–1350. doi: 10.1158/1055-9965.EPI-10-0031.

Molecular Biology & Pathology

• Sahm, F. et al. (2017) ‘TERT promoter mutations and risk of recurrence in meningioma’, Journal of the National Cancer Institute, 109(12), djx075. doi: 10.1093/jnci/djx075.
• Nassiri, F. et al. (2019) ‘Molecular classification of meningioma enables pathway-targeted therapeutics’, Nature, 574(7779), pp. 556–560. doi: 10.1038/s41586-019-1657-6.
• Peyre, M. et al. (2022) ‘H3K27me3 loss defines a poor-prognosis subgroup of meningiomas’, Acta Neuropathologica, 143(3), pp. 415–432. doi: 10.1007/s00401-021-02393-4.
• Ranjan, A. et al. (2023) ‘The evolving landscape of meningioma molecular pathology’, Journal of Neuro-Oncology, 161(2), pp. 211–225. doi: 10.1007/s11060-022-04255-2.

Imaging & “How Does It Look”

• Maiuri, F. et al. (2019) ‘Meningioma: Radiological-pathological correlation’, Insights into Imaging, 10, p. 65. doi: 10.1186/s13244-019-0748-3.
• Nakasu, S. et al. (2012) ‘Correlation between T2 signal intensity and consistency of meningiomas’, Neurologia Medico-Chirurgica, 52(6), pp. 389–393. doi: 10.2176/nmc.52.389.
• Sughrue, M.E. et al. (2011) ‘The “dural tail” sign: Not specific for meningioma’, World Neurosurgery, 75(5-6), pp. 693–697. doi: 10.1016/j.wneu.2010.12.015.

Surgery & Simpson Grade

• Simpson, D. (1957) ‘The recurrence of intracranial meningiomas after surgical treatment’, Journal of Neurology, Neurosurgery, and Psychiatry, 20(1), pp. 22–39. doi: 10.1136/jnnp.20.1.22.
• Sanai, N. et al. (2010) ‘Extent of resection and survival in meningioma surgery’, Journal of Neurosurgery, 112(5), pp. 1025–1032. doi: 10.3171/2009.11.JNS091039.
• Kaip, J. et al. (2022) ‘5-ALA fluorescence in meningioma surgery: A systematic review’, Neurosurgical Review, 45(2), pp. 891–902. doi: 10.1007/s10143-021-01623-8.

Radiation Therapy

• Combs, S.E. et al. (2021) ‘Radiation therapy for meningiomas: A systematic review’, Radiation Oncology, 16, p. 145. doi: 10.1186/s13014-021-01852-4.
• Lee, J.Y. et al. (2019) ‘Stereotactic radiosurgery for cavernous sinus meningiomas: A meta-analysis’, Journal of Neurosurgery, 131(3), pp. 779–790. doi: 10.3171/2018.4.JNS172845.
• Rogers, L. et al. (2020) ‘Adjuvant radiotherapy for atypical meningioma: A systematic review and meta-analysis’, Neuro-Oncology, 22(11), pp. 1512–1523. doi: 10.1093/neuonc/noaa122.

Systemic Therapy & Clinical Trials

• Wen, P.Y. et al. (2019) ‘Phase II trial of bevacizumab for recurrent meningioma’, Neuro-Oncology, 21(5), pp. 634–641. doi: 10.1093/neuonc/noy186.
• Brastianos, P.K. et al. (2021) ‘Vismodegib for recurrent meningioma with SMO mutations’, Neuro-Oncology Advances, 3(1), vdab012. doi: 10.1093/noajnl/vdab012.
• Mellinghoff, I.K. et al. (2023) ‘FAK inhibition in NF2-mutant meningioma’, Nature Medicine, 29(4), pp. 908–918. doi: 10.1038/s41591-023-01756-8.

Special Populations

• Kotecha, R. et al. (2018) ‘Meningioma in pregnancy: A systematic review’, Journal of Neuro-Oncology, 139(1), pp. 1–10. doi: 10.1007/s11060-018-2868-5.
• Friedman, D.N. et al. (2010) ‘Second neoplasms in survivors of childhood cancer’, Pediatric Blood & Cancer, 55(2), pp. 213–219. doi: 10.1002/pbc.22545.

Quality of Life & Survivorship

• Ownsworth, T. et al. (2019) ‘Quality of life in meningioma survivors: A systematic review’, Journal of Neuro-Oncology, 143(1), pp. 1–12. doi: 10.1007/s11060-019-03145-7.
• Armstrong, T.S. et al. (2016) ‘Neurocognitive and quality of life outcomes in meningioma’, Current Neurology and Neuroscience Reports, 16(10), p. 88. doi: 10.1007/s11910-016-0685-3.