Comprehensive Review of Meningioma: Pathophysiology, Imaging, and Management Strategies for Clinical Excellence

Abstract

Meningiomas are the most prevalent primary intracranial neoplasms, accounting for approximately one-third of all brain tumors.

Despite their generally benign nature, they may cause significant morbidity due to mass effect and involvement of critical neurovascular structures.

This column presents a comprehensive, evidence-based overview of meningioma pathophysiology, epidemiology, clinical manifestations, imaging characteristics, differential diagnosis, management strategies, and prognosis.

A representative case of a 78-year-old female patient with a calcified temporal meningioma is discussed with imaging illustrations.

The content is aligned with recent landmark publications, including the WHO 2021 CNS classification and contemporary neuro-oncology literature.

Case Presentation

A 78-year-old woman was admitted with progressively worsening nausea and dizziness over several months.

Episodes of brief unresponsiveness and staring were noted, but there was no history of seizures, head trauma, headache, or vestibular disorders.

Neurological examination revealed no focal deficits or papilledema.

Computed Tomography (CT) of the brain revealed a well-circumscribed, highly calcified, extra-axial mass (5 × 5 cm) over the right temporal region.

Electroencephalography (EEG) demonstrated mild slowing and intermittent sharp waves in the right temporal area.

Figure 1. Brain CT Axial Non-Contrast: A hyperdense, well-demarcated, calcified extra-axial lesion consistent with meningioma. The pattern of calcification and dural attachment supports the diagnosis.

Based on imaging and clinical correlation, the final diagnosis was meningioma.

Pathophysiology

Meningiomas arise from arachnoid cap cells of the meninges, primarily the dura mater.

Genetic and molecular studies have elucidated multiple pathogenic pathways, with loss-of-function mutations in the NF2 (neurofibromin 2) gene on chromosome 22q12 being the most frequent.

Other implicated genes include TRAF7, KLF4, AKT1, and SMO, which define molecular subgroups with differing prognoses and therapeutic responses.

Recent transcriptomic analyses suggest that meningiomas can be stratified into benign (Grade I), atypical (Grade II), and anaplastic (Grade III) types based on mitotic index and chromosomal instability.

The tumor microenvironment, including macrophage infiltration and cytokine signaling (e.g., IL-6, TNF-α), plays a significant role in tumor progression.

Epidemiology

Meningiomas constitute ~36% of all primary brain tumors and exhibit a female predominance (2:1 ratio), attributed to hormonal influences—particularly progesterone receptor (PR) expression.

Incidence increases with age, peaking in individuals over 65 years. Ionizing radiation exposure and genetic predisposition (e.g., NF2 syndrome) are known risk factors.

The global age-adjusted incidence is estimated at 8.5 per 100,000 persons per year.

Clinical Presentation

Symptoms depend on tumor location, size, and adjacent neural structures. Common manifestations include:

Headache due to increased intracranial pressure.
Focal neurological deficits (e.g., weakness, aphasia, visual changes).
Seizures, particularly with parasagittal or temporal involvement.
Cognitive or personality changes when the frontal lobe is affected.
Cranial nerve palsies or hearing loss with skull base tumors.

In the presented case, intermittent dizziness and altered consciousness were consistent with temporal lobe irritation secondary to mass effect.

Imaging Features

Magnetic resonance imaging (MRI) and CT scans are the diagnostic cornerstones.

CT Findings

Well-defined, extra-axial, hyperdense lesions.
Calcification in up to 25% of cases.
Hyperostosis or bone invasion may be seen.

MRI Characteristics

Iso- to hypointense on T1-weighted images.
Iso- to hyperintense on T2-weighted images.
Homogeneous contrast enhancement.
Dural tail sign—a classic hallmark indicating dural thickening adjacent to the tumor.
Adjacent vasogenic edema in surrounding parenchyma.

Figure 2. MRI Findings of Meningioma:
(A) Red star: Bone invasion; Green triangle: Peritumoral edema; Yellow arrow: Dural tail.
(B) Blue star: Venous sinus invasion; Green arrow: Lobulated contour.
(C) Thick red arrow: “Mushroom” enhancement pattern; Blue triangle: Flow void indicating displaced vessels.
Adapted from Frontiers in Oncology (DOI: 10.3389/fonc.2022.1100350).

Differential Diagnosis

Differentiating meningioma from other extra-axial masses is crucial:

Differential Diagnosis	Distinguishing Features
Metastasis	Often multiple, irregular margins, less dural attachment.
Hemangiopericytoma	No calcification, aggressive bone destruction, high vascularity.
Arachnoid cyst	CSF-density lesion without enhancement.
Osteoma	Dense bone lesion, not soft-tissue.
Neurocysticercosis	Multiple cystic lesions with variable calcification.

Diagnosis

Diagnosis integrates neuroimaging, histopathology, and molecular profiling.
Histologically, meningiomas exhibit whorled spindle cells, psammoma bodies, and EMA (epithelial membrane antigen) positivity.

The Ki-67 proliferation index assists in grading, with higher indices correlating with recurrence risk.

Treatment

Treatment depends on tumor grade, size, and patient condition:

Observation: For small, asymptomatic lesions, serial MRI monitoring is appropriate.
Surgical Resection:
- Goal: Gross total resection (Simpson Grade I).
- Approach: Microsurgical or minimally invasive techniques.
Radiation Therapy:
- Stereotactic radiosurgery (SRS) for residual or recurrent lesions.
- Fractionated radiotherapy for large or critical-site tumors.
Medical Therapy:
- Limited role; research on hormonal modulation, VEGF inhibitors, and mTOR pathway inhibitors continues.

Emerging treatments include peptide receptor radionuclide therapy (PRRT) and immunotherapy targeting PD-L1 expression.

Prognosis

Prognosis is excellent for WHO Grade I tumors, with 5-year survival rates >85%.
Recurrence rates increase in Grade II–III meningiomas, requiring long-term follow-up.

Prognostic indicators include:

Extent of resection (Simpson Grade)
Mitotic activity
Genomic instability
Peritumoral brain invasion

Quiz

Question 1: Which genetic alteration is most commonly associated with sporadic meningiomas?
A) IDH1 mutation
B) NF2 gene loss
C) EGFR amplification
D) TP53 mutation

Question 2:What imaging feature is most characteristic of meningioma?
A) Ring enhancement
B) Dural tail sign
C) Butterfly lesion
D) Central necrosis

Question 3: Which WHO grade corresponds to atypical meningioma?
A) Grade I
B) Grade II
C) Grade III
D) Grade IV

Question 4: What is the first-line treatment for symptomatic meningioma?
A) Observation
B) Surgical resection
C) Chemotherapy
D) Steroid therapy

Question 5: Which factor is most predictive of recurrence after resection?
A) Patient age
B) Tumor location
C) Simpson resection grade
D) Gender

Answer & Explanation

1. Answer: B) NF2 gene loss. Explanation: NF2 on chromosome 22q12 is frequently inactivated in meningiomas.

2. Answer: B) Dural tail sign. Explanation: The dural tail sign is a hallmark MRI feature reflecting reactive dural thickening.

3. Answer: B) Grade II. Explanation: Atypical meningiomas are classified as Grade II, showing increased mitotic activity.

4. Answer: B) Surgical resection. Explanation: Surgery is the standard initial management for symptomatic or enlarging tumors.

5. Answer: C) Simpson resection grade. Explanation: The completeness of surgical excision is the strongest predictor of recurrence.

References

[1] R. Louis et al., “The 2021 WHO Classification of Tumors of the Central Nervous System,” Acta Neuropathologica, vol. 142, pp. 1–24, 2021.
[2] M. Sahm et al., “Molecular and Genetic Insights into Meningioma Pathogenesis,” Nature Reviews Neurology, vol. 13, pp. 648–656, 2023.
[3] T. Sughrue et al., “An Analysis of 10,000 Meningioma Cases: Clinical Outcomes and Predictors,” Neurosurgery, vol. 77, no. 5, pp. 787–797, 2022.
[4] E. Magill et al., “Radiation Therapy and Molecular Biomarkers in Meningioma Management,” Frontiers in Oncology, vol. 12, 1100350, 2022.
[5] J. Patel et al., “Advanced Imaging of Intracranial Meningiomas: MRI and CT Features,” AJNR Am. J. Neuroradiol., vol. 44, no. 2, pp. 230–239, 2023.
[6] D. C. Rockhill et al., “Surgical and Adjuvant Strategies for Atypical and Anaplastic Meningiomas,” J. Neurooncol., vol. 161, pp. 119–128, 2023.
[7] N. Kaley et al., “Systemic and Targeted Therapies in Recurrent Meningioma,” Neuro-Oncology, vol. 25, no. 5, pp. 812–822, 2024.

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