Meningioma

Meningioma is a typically benign, slow-growing tumour arising from the meninges, more common in females and often presenting with cellular whorls and psammoma bodies on microscopy and calcification or ‘dural tail’ sign on neuroimaging.

Description

Meningiomas are the most common primary intracranial tumours, accounting for about 30% of all such cases. They originate from the meningothelial cells of the arachnoid (the middle layer of the meninges). Meningiomas are typically benign (WHO grade I), slow-growing, and are more prevalent in females.

Pathogenesis

Most meningiomas arise spontaneously, but some are associated with certain genetic conditions, such as neurofibromatosis type 2 (NF2). The most common genetic alteration in sporadic meningiomas involves chromosome 22q, where the NF2 gene is located. Hormonal factors may also play a role, as these tumours are more common in women, and some express estrogen/progesterone receptors. Radiation exposure is another identified risk factor.

Subtypes

Meningiomas can be classified into 15 histological subtypes. The most common are:

• Meningothelial (most common, 50% of all meningiomas)
• Fibrous (fibroblastic)
• Transitional (mixed)
• Psammomatous
• Angiomatous

Epidemiology, Risk Factors & Associations

• Typically present in adults, with a peak incidence in the 5th to 7th decades of life. They are rare in children, accounting for less than 2% of all cases.
• More common in females, with a female-to-male ratio of approximately 2:1.
• Slightly more prevalent in African Americans compared to other races.

Risk factors include:

• Neurofibromatosis type 2 (NF2/MISME): Predisposition to develop multiple meningiomas. Mutations in the neurofibromin 2 (NF2) gene, located on chromosome 22, are associated with a substantial subset of sporadic and virtually all NF2-associated meningiomas.
• Radiation exposure: Previous exposure to ionising radiation, particularly during childhood, significantly increases the risk of meningioma development.
• Inherited syndromes: Although rare, certain inherited syndromes such as multiple endocrine neoplasia type 1 (MEN1) and Gorlin syndrome (nevoid basal cell carcinoma syndrome) have been associated with an increased risk of meningiomas.

Clinical Features

Meningiomas can be asymptomatic and discovered incidentally. When symptoms occur, they depend on the tumour location and size. Common presentations include headache, seizures, and focal neurological deficits corresponding to the area of the brain compressed by the tumour.

Pathological Features

Histopathology

• Gross: typically well-demarcated, lobulated tumors that may be attached to the dura mater. The tumours are often firm and greyish-pink in color. The cut surface of the tumor is typically whorled or homogeneous. Psammoma bodies (concentrically calcified structures) are often seen in psammomatous subtype.

Histopathologically, meningiomas can be divided into three grades (WHO I, II, III), which help predict the prognosis and guide treatment. The atypical (WHO Grade II) and anaplastic (WHO Grade III) meningiomas are less common and have more aggressive behaviour and a higher recurrence rate.

• Grade I (benign): These are slow-growing tumors that form concentric whorls and psammoma bodies (laminated calcifications) can be seen. The cells are uniform with no evidence of anaplasia.
• Grade II (atypical): These tumors show increased cellularity, small cells with high nuclear:cytoplasmic ratio, prominent nucleoli, and up to 20 mitoses per 10 high-power fields. They also show evidence of brain invasion.
• Grade III (anaplastic/malignant): These tumors show frank anaplasia and/or malignant features similar to carcinomas or sarcomas, and they have >20 mitoses per 10 high-power fields.

Immunohistochemistry

• The tumour cells are typically positive for epithelial membrane antigen (EMA) and vimentin. They are also often positive for progesterone receptors.

Genetics

• Chromosome 22 deletions can be seen

Radiological Features

General Features

• Extra-axial dural-based lesion, most commonly found along the superior sagittal sinus, convexity, sphenoid wing, and parasagittal region.
• They are typically round or lobulated, extra-axial masses that may cause scalloping of the inner table of the skull. They may have a broad-based dural attachment, often with a characteristic ‘dural tail’ on contrast-enhanced images.
• Meningiomas may cause vasogenic oedema in the adjacent brain parenchyma. They can also cause local mass effect and even lead to midline shift in larger cases. May cause bone hyperostosis due to vasoactive factors.
• Vividly enhances on and often demonstrates a dural tail sign.
• Parasellar meningioma may encase and narrow the cavernous or supraclinoid internal carotid artery.

CT

• They are usually round or lobulated masses that may show calcification.
• Can cause bone hyperostosis or scalloping of the inner table of the skull.
• Meningiomas are typically isodense to slightly hyperdense compared to the adjacent brain tissue on non-contrast images.
• After contrast administration, they demonstrate avid, homogeneous enhancement.

MRI

• T1: Usually isointense to slightly hypointense compared to grey matter
• T2: Isointense to hypointense
• FLAIR: Variable intensity, often hyperintense due to vasogenic edema
• T1 Gad+: Strong, homogeneous enhancement. Some larger tumors may have a non-enhancing necrotic center.
• T2*/GRE: Calcifications appear as low signal intensity

XA

• Meningiomas often appear as hypervascular masses with a characteristic “sunburst” or “spoke wheel” pattern of vessels due to the blood supply for external carotid artery branches.

NM

• FDG-PET: Meningiomas usually show low to moderate uptake of FDG.
• DOTATATE-PET: High uptake due to the high expression of somatostatin receptors in meningiomas. This is useful for detecting meningioma metastasis or multifocal disease.

Grading and Staging

Meningiomas are graded by the WHO criteria into Grade I (benign), Grade II (atypical), and Grade III (anaplastic/malignant) based on certain histopathological features. Higher-grade tumours have a higher recurrence rate and worse prognosis.

Differential Diagnosis

• Schwannoma: Often located in the cerebellopontine angle and associated with cranial nerve VIII, unlike meningiomas, which are typically attached to the dura mater. They show similar intensity on T1- and T2-weighted MRI images and also enhance with contrast. However, schwannomas are often associated with cystic components and intratumoral hemorrhage, which are less commonly seen in meningiomas.
• Metastasis: Similar to meningiomas, metastases can enhance on contrast imaging. However, multiple lesions are more commonly seen with metastasis, while meningiomas are usually solitary. Furthermore, metastases are typically intra-axial, whereas meningiomas are extra-axial.
• Glioblastoma: These are typically intra-axial, unlike meningiomas, and often exhibit central necrosis with a ring of enhancement on contrast-enhanced imaging. Glioblastomas often demonstrate significant peritumoral edema.
• Primary CNS lymphoma: Usually occurs in immunocompromised individuals, and is more commonly intra-axial. It is typically homogeneously enhancing on contrast imaging and does not have a ‘dural tail,’ which is characteristic of meningiomas.
• Haemangiopericytoma: These are aggressive tumors that can resemble meningiomas on imaging. However, they often appear more irregular and infiltrative and may show greater heterogeneous enhancement and flow voids on contrast-enhanced imaging.
• Sarcoidosis: Granulomas of sarcoidosis can mimic meningiomas, but typically multiple lesions are seen, and there is associated meningeal and cranial nerve involvement. Sarcoid lesions may show intense homogeneous enhancement but lack the ‘dural tail’ sign.
• Solitary Fibrous Tumor (SFT): They can be challenging to differentiate from meningiomas as they share similar imaging characteristics, such as isointensity on T1 and T2, and homogeneous enhancement post-contrast. SFTs are typically hypervascular and may have large feeding vessels visible on angiography. Additionally, SFTs usually lack calcification and hyperostosis, which can be seen in meningiomas.

Management

Management depends on the patient’s symptoms, tumour size, and location. Asymptomatic small tumours may be monitored. Symptomatic or larger tumours often require surgical resection. Radiotherapy may be used for unresectable tumours or as adjuvant therapy for higher-grade tumours or those with subtotal resection. Regular surveillance imaging is required due to the risk of recurrence, especially for higher-grade tumours.