Meningioma

General

A group of mostly benign,

Slow-growing neoplasms that

Most likely derive from the meningothelial cells of the arachnoid layer.

Definition

Essential

Classic histopathological features matching at least one of the meningioma subtypes OR
Suggestive histopathological features combined with biallelic inactivation of NF2 or other classic drivers of conventional meningioma (TRAF7, AKT1, KLF4, SMO, PIK3CA), clear cell meningioma (SMARCEf), or rhabdoid meningioma (BAP1) OR
Suggestive histopathological features combined with one of the defined DNA methylation classes of meningioma

Desirable

Meningeal localization
EMA immunoreactivity
Strong and diffuse SSTR2A immunoreactivity
Classic copy-number alterations of NF2-mutant meningioma, such as monosomy 22/22q in lower-grade meningiomas, with additional losses of 1p, 6, 10q, 14q, and/or 18 in higher-grade meningiomas

CNS WHO grading

Grade II

4 to 19 mitotic figures in 10 consecutive HPF of each 0.16 mm2 (at least 2.5/mm2) OR
Unequivocal brain invasion (not only perivascular spread or indentation of brain without pial breach) OR
Specific morphological subtype (chordoid or clear cell; see text) OR
At least three of the following:

Increased cellularity
Small cells with high N:C ratio
Prominent nucleoli
Sheeting (uninterrupted patternless or sheet-like growth)
Foci of spontaneous (non-iatrogenic) necrosis

Grade III

20 or more mitotic figures in 10 consecutive HPF of each 0.16 mm2 (at least 12.5/mm2) OR
Frank anaplasia (sarcoma-, carcinoma-, or melanoma-like appearance) OR
TERT promoter mutation OR
Homozygous deletion of CDKN2A and/or CDKN2B

ㅤ	Grade I	Grade II	Grade III
Prevalence	~85-95%	~5-10%	~1-5%
Demographics	ㅤ	ㅤ	ㅤ
Gender	Female > Male	Female ≥ Male	Female ≤ Male
Diagnostic Criteria	Mitoses < 4/10 hpf	Mitoses 4-19/10 hpf OR 3/5 of the following: - Necrosis - High nuclear/cytoplasmic ratio - Prominent nucleoli - Architectural sheeting - Hypercellularity OR Clear cell/chordoid histology OR Brain Invasion	Mitoses ≥ 20/10 hpf OR Frank anaplasia OR Papillary/rhabdoid histology
Histologic Subtypes	- Meningothelial - Fibrous (Fibroblastic) - Transitional (Mixed) - Psammomatous - Angiomatous - Microcystic - Secretory - Lymphoplasmacyte-rich - Metaplastic	- Atypical - Chordoid - Clear cell	- Anaplastic - Papillary - Rhabdoid
Clinical Outcomes at 10yrs	ㅤ	ㅤ	ㅤ
Overall Survival	80-90%	50-79%	14-34%
Progression-free survival	75-90%	23-78%	0%

Cytogenetic changes during initiation and progression of meningiomas.

Ostrom et al., 2016

WHO grade	F:M ratio	Recurrence rate 5yrs (Choy 2011)	5yrs survival rate (Palma 1997)	10yrs survival rate (Palma 1997)
1	2.3	5%
2	1.2	40%	95%	79%
3	1.1	80%	64%	35%

Number

36% of all adult brain

2.8% of all pediatric primary brain tumors

> 90% of all meningiomas are solitary

Multiple meningiomas

These can be seen in 1– 9% of meningiomas, occurring more frequently in females and do not necessarily indicate association with NF2 syndrome (Terrier and François, 2016). They can arise at different times. Multiple lesions may be seen with radiation- induced meningiomas.

Age

Median age: 65
Risk increasing with age

Inc. imaging usage

Un common in children Kotecha et al., 2011

1.5% of the total,
Extremely rare in infants
Childhood meningiomas Males>females, 1.3:1 ratio
15– 25% of childhood meningioma cases are associated with NF2

Age-adjusted incidence rates vary significantly by sex

Females greater risk than males:

Annual incidence rates

10.5/100,000 females
4.8/100,000 males

This difference is greatest prior to menopause, with the highest female to-male ratio (3.15:1) in the 35-44 years age group
Grade II and III lesions occur at higher rates in males

Race

Annual incidence rates per 100 000 population of

Blacks: 9.1
Whites: 7.4
Asians: 4.8

A graph of a person and person AI-generated content may be incorrect. — Age- and sex-specific incidence rates (per 100,000 population) of meningioma in the USA (2002-2006). The left scale refers to the bar graph, the right scale refers to the female-to-male incidence ratio, which is indicated for each age group by a diamond.

Cell of origin

Meningothelial (arachnoid) cells.

Very rare extradural meningiomas are thought to arise either as an entrapment of meningothelial cells or from some other ‘stem- like’ cell (Lang et al., 2000)
Meninges development

Aetiology

Ionising radiation

Only established environmental risk factor

Higher risk among people who were exposed in childhood than as adults

CT>X-rays have greater risk of brain tumours (glioma and meningioma)

Radiation therapy induces five times more meningiomas than it does gliomas or sarcomas.

Definition of radiation induced meningioma

Meningioma arises in the radiation field,
Appears after a latency period (up to 35 years),
Was not the primary tumour irradiated
Not seen in a patient with SPS (NF2).

Multiple meningiomas occur in

30% of previously irradiated patients with meningiomas
1% to 2% of nonirradiated patients with meningiomas.

Higher risk of recurrence than non irradiated ones

Bowers et al., 2017:

Childhood cancer survivors receiving cranial radiotherapy, the cumulative incidence of a subsequent meningioma by the age of 40 years was 5.6% with a median interval from primary cancer to meningioma diagnosis of 22 years and increased risk correlating with increased radiation dose.

Progesterone receptors

Present in most meningiomas

Higher risk in women vs men

Gene mutation with increase susceptibility to meningiomas

DNA repair genes:

BRIP1 {17q22}, the gene encoding the FACJ protein, which interacts with BRCA1

Gorlin syndrome patients (germline SUFU or PTCH1 mutations)

MLLT10 is implicated in various leukaemias and activates the WNT pathway.

Modestly increased risk

Use of endogenous/exogenous hormones

Body mass index

Current smoking

Decreased risk

Breastfeeding for > 6 months

Allergic conditions (e.g. asthma and eczema)

Localisation

Vast majority

Intracranial

Cerebral convexities (with tumors often located parasagittal, in association with the falx and venous sinus)

Atypical and anaplastic meningiomas most commonly affect the convexities and other non-skull base sites

Olfactory grooves
Sphenoid ridges
Para-/suprasellar regions

Tuberculum sellae

How to differentiate between meningioma and pituitary tumour

Meningiomas do not expand the sellae I. E. It has a normal sella
Meningiomas have a dural tail

Optic nerve sheath
Petrous ridges
Tentorium
Posterior fossa

Intraspinal

Thoracic region

Orbital

Rare

Intraventricular (4% of all intracranial meningiomas)

Trigone of lateral ventricle

Lt>Rt
Significant feeding vessel that on MRI is seen to enter the tumour, usually a branch from one of the choroidal arteries

Post 3rd ventricle

Arachnoid cap cells from vellum interpositum

Fourth ventricle

Arachnoid cap cells within the choroid plexus

Treatment options (depending on the size and clinical picture) include

Surgery
SRS
Surveillance

Epidural

Classification

Reference: Lynes 2022

Based on genetic mutations

Genetic mutation subgroup	Clinical features
NF2	- Most common, larger, more aggressive course. - Highest seizure risk. - Male predominance - Falcotentorial location
TRAF7	- Second most common. - Associated with higher grade. Higher likelihood of hyperostosis - Midline and lateral skull base location
TRAF7 with KLF4	- High peritumor edema - Midline and lateral skull base location
PI3K Pathway	- Low recurrence risk - Midline and lateral skull base location
HH pathway	- Less aggressive, low grade - Localize to midline anterior skull base
PPOL-R2A	- Benign, female predominance. - Sella, clivus, and posterior fossa location
SMARCE1	- High recurrence risk, faster growth. - Lateral skull base, anterior falcine location

Based on transcriptome analysis

Transcriptome subtypes	Features
Type A	- Low proliferation index. - Anterior skull base. - 2:1 female to male. - No significant chromosomal changes. - Only type with TRAF7. High prevalence of KLF4 and AKT1. No NF2 mutations.
Type B	- Intermediate proliferation index. - 2:1 female to male. - Significant prevalence of loss of chr22q. - NF2 mutations. Highest prevalence of SMARCB1.
Type C	- High proliferation index. - Falcine, occipital regions. - 56% male. - Significantly shorter PFS than Type A or B irrespective of WHO grade. - In addition to NF2, numerous chromosomal abnormalities.

Clinical features

Headache: 36%

Paresis: 22%

Change in mental status: 21%

Compression of adjacent structures

Supratentorial: 85-90%

Parasagittal, convexities: 45%

Seizures and hemiparesis

Sphenoid ridge: 15-20%
Olfactory groove/planum sphenoidale: 10%

Anosmia (usually not recognized)

Juxtasellar: 5-10%

Visual field defects
Cranial nerve deficits

Infratentorial: 5-10%

Obstructive hydrocephalus
Cranial nerve deficits

Miscellaneous intradural: <5%

Intraventricular meningioma
Optic nerve meningioma
Pineal gland

Parinaud syndrome
Obstructive hydrocephalus

Hyperostosis → local mass effect → proptosis

Slow growing

Gradual dural venous sinus invasion + occlusion → collateral veins have had time to enlarge → asymptomatic

Seizures

Radiographic features

General

Lytic/destructive regions are seen particularly in higher grade tumours but should make one suspect alternative pathology (e.g. haemangiopericytoma or metastasis)

Appear as extra-axial masses with a broad dural base. They are usually homogeneous and well-circumscribed

Substantial peritumoural oedema can be seen, especially in secretory and high-grade subtypes.

Special examples' of meningiomas

Burnt out meningioma
Cystic meningiomas
Intraosseous meningioma
Intraventricular meningioma
Optic nerve sheath meningioma
Radiation-induced meningioma

Helpful imaging signs

CSF cleft sign

A sign that lesion is extra-axial

Not specific for meningioma

Loss of this can be seen in grade II and grade III which may suggest brain parenchyma invasion

The cleft contains one or more of the following:

Cerebrospinal fluid (CSF) between the lesion and the underlying brain parenchyma,
Hypointense dura (made of fibrous tissue), and
Marginal blood vessels trapped between the lesion and the brain

CSF CLEFT SIGN mass Meniscus Dura draped over lesion Vessels pushed inward Gray and white matter buckled inward FIGURE 3-1. Extra-axial lesion signs. A, A skull-based extradural mass is depicted diagrammatically, producing a meniscus sign, displacement of the subarachnoid veins inward, and buckling of the gray-white interface. Dura may be seen stretched over the mass. B, Extra-axial mass. The classic extra- axial mass (M) expands the subarachnoid space at its borders (straight arrows), has a dural base (arrowheads), and displaces blood vessels in the subarach- noid space medially (curved arrow). This was a vestibular schwannoma, but on the top image it could just as easily be a meningioma with that dural base. Notice the extension into the internal auditory canal on the lower image (open arrow). — Extra-axial lesion signs. (A) A skull-based extradural mass is depicted diagrammatically, producing a meniscus sign, displacement of the subarachnoid veins inward, and buckling of the gray-white interface. Dura may be seen stretched over the mass. (B) Extra-axial mass. The classic extra-axial mass (M) expands the subarachnoid space at its borders (straight arrows), has a dural base (arrowheads), and displaces blood vessels in the subarachnoid space medially (curved arrow). This was a vestibular schwannoma, but on the top image it could just as easily be a meningioma with that dural base. Notice the extension into the internal auditory canal on the lower image (open arrow).

Dural tail

Seen in 60-72% of meningiomas

Dural tail differential (My Scary Dog Likes To Stand Guard)

M: Meningioma
S: Sarcoidosis
D: Dural metastases
L: Lymphoma
T: Tuberculoma
S: Schwannoma
G: Glioma

Due to

Neoplastic infiltration of the meninges by the meningioma or
Reactive fibrovascular proliferation of the underlying meninges.

FIGURE 3-3. Parasagittal meningioma. A, This meningioma is really dark on T2-weighted image but the adjacent bright cerebrospinal fluid (CSF) demonstrates its extra-axial location nicely (CSF cleft sign designated by arrows). B, Add a dural tail (arrows) and strong enhancement, and you should be dictating this case as a meningioma. — Parasagittal meningioma. (A) This meningioma is really dark on T2-weighted image but the adjacent bright cerebrospinal fluid (CSF) demonstrates its extra-axial location nicely (CSF cleft sign designated by arrows). (B) Add a dural tail (arrows) and strong enhancement, and you should be dictating this case as a meningioma.

Sunburst or spoke-wheel appearance

Description of the meningioma vessels

Dural arteries supplying the meningioma

Sunburst appearance. T1 weighted brain MRI, coronal view (A), left parietal hemisphere lesion with spoke wheel pattern of vessels supplying a meningioma. This characteristic vascular supply resembles a sunburst (orange rectangle). (B) View of the Remote Manipulator System (RMS) end effector over an Earth limb with a solar sunburst pattern behind it. By NASA (Great Images in NASA Description) [Public domain], via Wikimedia Commons.

White matter buckling sign

Helpful in distinguishing an extra-axial vs intra-axial one

Due to white matter projecting into gyri being compressed and displaced by the mass, even in the presence of oedema (which would usually expand gyri, if the mass were intra-axial)

A close-up of a brain scan AI-generated content may be incorrect.

Arterial narrowing

Typically seen in meningiomas which encase arteries

Useful sign in parasellar tumours, in distinguishing a meningioma from a pituitary macroadenoma (does not narrow vessels)

Oedema

Present in >50% meningiomas

When severe likely

Aggressive meningiomas
Secretory variant meningiomas: oedema can be disproportionately larger than the small tumour size.

List of some of the proposed underlying mechanisms are:

Venous stasis/occlusion/thrombosis
Compressive ischaemia
Aggressive growth/invasion
Parasitisation of pial vessels

Invasion of pial vessels

Secretory meningioma
Vascular endothelial growth factor (VEGF): produced within the meningioma that enters the adjacent parenchyma
Expression of CEA and CK

Plain radiograph

No longer have a role

Historical features

Enlarged meningeal artery grooves
Hyperostosis or lytic regions
Calcification
Displacement of calcified pineal gland/choroid plexus due to mass effect

CT

Non-contrast CT

60% slightly hyperdense to normal brain, the rest are more isodense
20-30% have some calcification

Post-contrast CT

72% brightly and homogeneously contrast enhance
Malignant or cystic variants demonstrate more heterogeneity/less intense enhancement

Hyperostosis (5%)

Common for base of the skull
Need to distinguish reactive hyperostosis from:

Direct skull vault invasion by adjacent meningioma
Primary intraosseous meningioma

A ct scan of a brain AI-generated content may be incorrect. — CT

Enlargement of the paranasal sinuses (pneumosinus dilatans) has also been suggested to be associated with anterior cranial fossa meningiomas

Ball valve mechanism at the level of the sinus ostia leading to the sinus expansion.

MRI

T1

80% Isointense to grey matter

20% hypointense to grey matter

Particularly fibrous, psammomatous variants

T1 C+: usually intense and homogeneous enhancement

T2

50% isointense to grey matter

40% hyperintense to grey matter (35-40%)

Correlates with a soft texture and hypervascular tumours
Seen in specific variants

Microcystic,
Secretory,
Cartilaginous (metaplastic) choroid
Angiomatous variants

10% hypointense to grey matter:

Correlates with harder texture and more fibrous and calcified contents

DWI/ADC

Atypical and malignant subtypes may show restricted diffusion but has not been useful in predicting grade

Images

A mri of a brain AI-generated content may be incorrect. — T1+C fat sat

A close-up of a mri scan AI-generated content may be incorrect. — DWI in a different tumour

MR spectroscopy

Does not play a significant role in diagnosis but can help distinguish meningiomas from mimics.

Features include:

Increase in alanine (1.3-1.5 ppm)
Increased glutamine/glutamate
Increased choline (Cho): cellular tumour
Absent or significantly reduced N-acetylaspartate (NAA): non-neuronal origin
Absent or significantly reduced creatine (Cr)

MR perfusion

Good correlation between volume transfer constant (k-trans) and histological grade

Angiography (DSA)

Rarely diagnostic use

Used for preoperative embolization

Reduce intraoperative blood loss

Vascular microcytic variants
Tumours with large vessel

Remove the need to resect tumour

Skull base tumours

7-9 days pre op

High prevalence of complications associated with particles < 45–150 μm

Meningiomas can have a dual blood supply.

Meningeal vessels: majority

Causes the sunburst or spoke-wheel pattern

Pial vessel supply to the periphery of a tumour

Well known angiographic sign mother-in-law sign

Contrast blush "comes early, stays late, and is very dense"

Blood supply to meningiomas

Location of Meningioma	Commonly seen blood supply (origin of vessel)
Convexity	Middle meningeal artery (ECA) Artery of the falx (branch of ophthalmic artery)
Sphenoid wing	Middle meningeal artery (ECA)
Tentorium and cerebellopontine angle	Tentorial artery (artery of Bernasconi-Casanari) from meningohypophyseal trunk (ICA)
Olfactory groove	Branches from ophthalmic artery
Foramen magnum and clivus	Anterior meningeal artery (vertebral) Dorsal meningeal artery from meningohypophyseal trunk (ICA)
Posterior fossa dura and falx cerebelli	Posterior meningeal artery (vertebral and MMA or ascending pharyngeal branches)

ECA, external carotid artery; ICA, internal carotid artery; MMA, middle meningeal artery.

Histopathology

Macroscopy

Most meningiomas are rubbery or firm, well-demarcated, sometimes lobulated, rounded masses that feature broad Dural attachment

Invasion of dura or Dural sinuses is fairly common.

Invasion into the adjacent skull, inducing hyperostosis

Can encase cerebral arteries, but rarely infiltrate arterial walls

Can infiltrate the skin and extracranial compartments, such as the orbit.

Adjacent brain is often compressed but rarely frankly invaded.

In certain sites, particularly along the sphenoid wing, meningiomas may grow as a flat, carpet-like mass, a pattern called en plaque meningioma

Gritty on gross inspection, implying the presence of numerous psammoma bodies

Bone formation is far less common

Atypical and anaplastic meningiomas

Larger
Often has necrosis.

Close-up of a human body anatomy AI-generated content may be incorrect.

Microscopic

Of the subtypes in the WHO classification, the most common are meningothelial, fibrous, and transitional meningiomas

Most variants behave in a benign fashion

Ki-67 proliferation index correlate approximately with volume growth rate.

Index of > 20% are associated with death rates analogous to those associated with anaplastic meningioma
Index of > 4% have an increased risk of recurrence similar to that of atypical meningioma

Kunimatsu 2016

Meningothelial rosettes, which are composed mostly of cell processes and collagen, with or without a central gland-like lumen

15 meningioma variant chart

Meningioma variants	Definition	Incidence (%)	Genetic	Ki67/mitosis	T1+C (homo=homogenous	T2 (vs grey matter)	DWI	Other notable radio features	Prognosis	Notes	Images
Grade 1				ㅤ							ㅤ
Meningothelial	A classic and common variant of meningioma, with medium-sized epithelioid tumour cells forming lobules, some of which are partly demarcated by thin collagenous septa.	57.8	AKT1, TRAF7, SMO, or PIK3CA.	ㅤ	Homo	Iso>hyper>hypo	Similar to brain		9% recur	Most often in the anterior skull base Less likely to be driven by NF2 mutations Commonly found in the setting of • Chronic renal disease • advanced patient age, • arachnoiditis ossificans, • Spontaneous intracranial haemorrhage, • in patients with diffuse dural thickening and contrast enhancement on neuroimaging	See images
Fibrous	A variant of meningioma that consists of spindled cells forming parallel, storiform, and interlacing bundles in a collagen-rich matrix.	11.1	Deletions of chromosome 22q and mutations of the NF2 allele.	ㅤ	Homo	Iso>hyper>hypo	Similar to brain			Intercellular collagen seen may raise the differential diagnosis of solitary fibrous tumour / haemangiopericytoma (SFT/HPC), but only SFT/ HPC expresses nuclear STAT6 NF2 mutations and convexity locations are common	See images
Transitional	A common variant of meningioma that contains meningothelial and fibrous patterns as well as transitional features	10.4	Share DNA methylation characteristics and frequent chromosome 22 deletions with fibrous and psammomatous subtypes.	ㅤ	Homo	Iso>hyper>hypo	Similar to brain			Commonly have NF2 mutations Generally convexity based	See images
Psammomatous	A designation applied to meningiomas (usually of the transitional type) containing a predominance of psammoma bodies over tumour cells	3.8	KLF4 and TRAF7 mutations.	ㅤ	Homo > peripheral	Hypo > iso, hyper	Similar to brain	Dense calcification on CT, predilection for thoracic spine		Psammoma bodies merge → irregular calcified masses/bone occur in the thoracic spinal region of middle-aged to elderly women	See images
Angiomatous	Variant of meningioma that features numerous blood vessels, which often constitute a greater proportion of the tumour mass than do the intermixed meningioma cells.	1.6	High frequency of chromosome 5 gains.	ㅤ	Homo	Hyper, with edema	Possibly facilitated	Prominent hypervascularity Significant oedema		-Differential diagnosis: • Vascular malformations • Haemangioblastoma, ◦ Express inhibin alpha and brachyury rather than EMA and somatostatin receptor 2A in meningioma -These tumours are frequently associated with extensive peritumoural oedema that exceeds what is expected for the tumour size.	See images, images
Microcystic	A variant of meningioma characterized by cells with thin, elongated processes encompassing microcysts and creating a cobweb-like background	0.3	Share DNA methylation profiles with the metaplastic and angiomatous subtypes.	ㅤ	Homo > reticular	Hyper, with edema	Possibly facilitated	Obviously hypo on T1WI		Similar to angiomatous meningiomas, these tumours are often associated with significant cerebral oedema.	See images
Secretory	A variant of meningioma characterized by the presence of focal epithelial differentiation in the form of intracellular lumina containing periodic acid-Schiff-positive eosinophilic secretions called pseudopsammoma bodies.	1.5 Female predominance	KLF4/TRAF7 mutations	ㅤ	Homo	Hyper, with edema	Possibly facilitated	Predilection for skull base		Pseudopsammoma bodies show immunoreactivity for CEA and a variety of other epithelial and secretory markers, and the surrounding tumour cells are positive for both CEA and cytokeratin (only positive here but not positive in other meningiomas). associated with elevated blood levels of carcinoembryonic antigen that drop with resection and rise with recurrence	See images
Lymphoplasmacyte-rich or inflammation-rich	A rare variant of meningioma that features extensive chronic inflammatory infiltrates, often overshadowing the inconspicuous meningothelial component	1.1		ㅤ	Indistinct margin	Hyper to iso, with edema	Possibly restricted	En plaque meningioma		-Systemic haematological abnormalities, including hyperglobulinaemia and iron-refractory anaemia have also been reported -Plasma cells may be scant while macrophages often predominate in the infiltrate.	See images
Metaplastic	A variant of meningioma with striking focal or widespread mesenchymal components including osseous, cartilaginous, lipomatous, myxoid, and xanthomatous tissue, either singly or in combinations.	1.6		ㅤ	Various, depending on mesenchymal components	Various, depending on mesenchymal components	Various, depending on mesenchymal components			These alterations have no known clinical significance, and many probably do not constitute true metaplasia (e.g. lipid accumulation rather than true lipomatous metaplasia)	See images
Grade 2				ㅤ							ㅤ
Chordoid	A rare variant of meningioma that histologically resembles chordoma, featuring cords or trabeculae of eosinophilic, often vacuolated cells set in an abundant mucoid matrix.	1.4		ㅤ	Homo > hetero	Hyper	Facilitated diffusion	Occasionally resembles Castleman’s disease		-Patients have associated haematological conditions, such as anaemia or Castleman disease -It is characteristically a large, supratentorial tumour found in younger patients with an average age of 45 years. -Grade 2 because high chance of recurrence	See images
Clear cell	A rare variant of meningioma with a patternless (commonly) or sheeting architecture and round to polygonal cells with clear, glycogen-rich cytoplasm and prominent blocky perivascular and interstitial collagen.	1.1	SMARCE1	ㅤ	Hetero	Mixed iso- to hyper, with cyst and edema	Similar to brain	Relatively young patients, predilection for CP angle		Proclivity for the spinal cauda equina region and the cerebellopontine angle.	See images
Atypical	Intermediate grade between benign and malignant forms, 4 - 19 mitotic figures/10 HPF brain invasion At least three of the following features: • increased cellularity, • Small cells with a high nuclear-to-cytoplasmic ratio, • prominent nucleoli, • Loss of lobular architecture (i.e. uninterrupted patternless or sheet-like growth) • Foci of spontaneous (i.e. not iatrogenically induced) necrosis.	3.4		increased mitotic activity of 4 to 19 mitoses per 10 high-power fields.	Hetero	Mixed hyper to hypo	Restricted diffusion	Increased permeability	29% recur 10 year survival is 79% 26% will progress to malignant		See images
Grade 3			TERT promoter mutation and/or homozygous deletion of CDKN2A/B	ㅤ							ㅤ
Papillary	Presence of perivascular pseudopapillary pattern constituting most of the tumour. Associated with brain invasion and aggressive clinical behaviour including metastasis to the lung.	1.1 Often occurs in younger patients	Mutations in PBRM1 or BAP1	ㅤ	Hetero	Iso > hyper, with cyst and edema	Restricted diffusion	Lobulated margin			See images, images
Rhabdoid	An uncommon variant of meningioma that consists primarily of rhabdoid cells: plump cells with eccentric nuclei, open chromatin, a prominent nucleolus, and prominent eosinophilic paranuclear inclusions, appearing either as discernible whorled fibrils or compact and waxy	2.3 Pediatric patients	BAP1 tumour predisposition syndrome.	ㅤ	Homo > hetero	Hyper > iso, with cyst	No published data			SMARCB1 expression is retained	See images
Anaplastic (malignant)	A meningioma that exhibits overtly malignant cytology (resembling that of carcinoma, melanoma, or high-grade sarcoma) and/or markedly elevated mitotic activity	1.4	TERT promoter mutation, or homozygous CDKN2A/B deletion.	markedly elevated mitotic activity,	Hetero	Mixed hyper to hypo	Restricted diffusion	Increased permeability	50 - 94% recur Survival 2-5 yrs Occasional metastases beyond the CNS	Associated with aberrant CpG island hypermethylation profile	See images, images

Other morphological variants: currently insufficient evidence that these tumours constitute distinct variants

Meningiomas with

Oncocytic
Mucinous
Sclerosing
Whorling-sclerosing
GFAP-expressing,
Granulo filamentous inclusion-bearing features

Immunophenotype

Positive stains

Vimentin (strong)

Relatively nonspecific

EMA (may be weak or focal, 70%)

Less consistent in atypical and malignant lesions

Somatostatin receptor 2A

Strong and diffuse expression in almost all meningioma cases (including anaplastic meningiomas),
Also encountered in neuroendocrine neoplasm

S100

Most common in fibrous meningiomas, but is not usually diffuse (S100 is diffuse in schwannomas)

ProgR (60 - 70%, usually women, tumour may grow during pregnancy)

Negative stains

GFAP, OCT4 (germ cell tumour marker)

Molecular pathogenesis

See Perry 2004

Reference: Rashed 2020

Typical mutations by WHO grade and anatomical location

Grade I — 80% (OS10 – 80-90%)

Meningothelial

Fibrous

Transitional

Psammomatous

Angiomatous

Microcystic

Secretory

Lymphoplasmacyte-rich

Metaplastic

Grade II — 15-18% (OS10 – 50-79%)

Atypical

Chordoid

Clear Cell

Grade III — 2-4% (OS10 – 14-34%)

Rhabdoid

Papillary

Anaplastic

Genetic features

Karyotype abnormalities

Monosomy 22

Most frequent genetic abnormality, found in over 50 per cent of tumours.

Karyotypic abnormalities are more extensive in atypical and anaplastic meningiomas

Other cytogenetic changes

Chromosomal Deletion/Loss

1p (which is associated with poor outcome)
6q
9p
10
14q
18q (which occur in higher grade tumours)

Chromosomal gains reported in higher-grade meningiomas

1q
9q
12q
15q
17q
20q

SPS NF2 gene

Found in

100% of familial meningiomas associated with neurofibromatosis type 2
60% of sporadic meningiomas

Mech steps:

Small insertions or deletions or are nonsense mutations that affect splice sites
Create stop codons or result in frameshifts occurring mainly in the 5'most two thirds of the gene
Forming a truncated and non-function merlin protein (aka schwannomin)

Fq of NF2 mutations varies among variants:

Variants	Location	Fq of NF2 mutation
Fibroblastic and transitional	Convexity	High
Meningothelial, secretory, and microcystic	Skull base	Low

NF2 inactivation is an early tumorigenic event evident by the following:

Atypical and anaplastic meningiomas, (occurs in 70% of cases)
Benign fibroblastic and transitional meningiomas (occur in 70% cases)

After NF mutation occurs it creates genetic instability to induce further mutations

Radiation-induced meningiomas

Low fq of NF2 mutations and loss of chromosome 22 are lower,
Higher fq structural abnormalities of chromosome 1p are more common

Other genes

SMARCE1 mutations are linked to the clear cell subtype, while BAP1 inactivation is linked to the rhabdoid subtype.

LARGE

MN1

AP1B1

SMARCB1

AKT1 gene (AKT1 E17K)

13% of meningiomas

Mostly of meningothelial or transitional variant

Pathogenesis

Mutations in AKT1, TRAF7, SMO, and PIK3CA are mutually exclusive with NF2 mutations and often correlate with skull base locations.

TRAF7 gene

8-24% of all meningiomas

93-100% of secretory meningiomas

Occurring in combination with KLF4 mutations

SMO gene

4-5% of WHO grade I meningiomas,
Mainly in meningiomas located in the medial anterior skull base.

SMARCE1 mutations

Found in clear cell meningiomas

CDKN2A gene deletion

Due to deletions of the 9p21 region, where gene located
Associated with high grade malignant progression/anaplastic meningiomas/shortened survival
Adding CDKN2A/B loss to NF2 loss enhances the rate of formation of meningiomas, including high-grade forms

Overexpression of telomerase: some of the ways this happens

TERT promoter mutation

A method where higher-grade meningiomas can escape senescence
Associated with high grade malignant progression/anaplastic meningiomas/shortened survival

Meningiomas are monoclonal tumours

Using X chromosome inactivated/activation or to carry the same NF2 mutation meningiomas were proven to be monoclonal

If multiple meningiomas are present they tend to form thru dural spread

Image here shows all meningiomas are on one half of the dura hence supporting monoclonality of meningiomas

Close-up of a brown and black fungus AI-generated content may be incorrect.

Rare but multiclonal meningiomas can also develop

Germline mutations in the SMARCB1 gene can also give rise to multiple schwannomas and meningiomas

Meningioma. Schematic showing the distribution and evolution of genomic and expression characteristics in meningioma grades. Mutations are listed in the grey bars, with light grey indicating mutations occurring in meningiomas without NF2 alterations. Cytogenetic alterations are listed in the blue bars, and gene expression changes in green. Bar length indicates the relative frequency of an alteration within the given tumour grade. *SMARCE1 mutations have been found nearly exclusively in clear cell meningiomas. PGDS: prostaglandin D2 synthase–positive precursor cells in murine meningioma models.

Familial syndromes associated with meningiomas

Familial syndrome	Affected gene	Chromosome locus
Neurofibromatosis type 2	NF2	22q12
Familial schwannomatosis	SMARCB1	22q11.23
Multiple spinal meningiomas	SMARCE1	17q21.2
BAP1 tumor predisposition syndrome	BAP1	3p21.1
Gorlin syndrome (nevoid basal cell carcinoma syndrome)	PTCH1	9q22.3
Familial multiple meningiomas	SUFU	10q24.32
Rubinstein-Taybi syndrome	CREBBP	16p13.3
von Hippel-Lindau syndrome	VHL	3p25-26
Cowden disease	PTEN	10q23.31
Li-Fraumeni syndrome	TP53/CHEK2	17p13.1/22q12.1
Gardner syndrome	APC	5q21-22
Multiple endocrine neoplasia type 1	MEN	11q13
Werner syndrome	LMNA	1q21.1

Management

Management option depends on

Age

Size

Location

The proximity of the tumour to important structures, such as cranial nerves,

Potential morbidity of the treatment and its effectiveness at the time of discovery

Psychological impact of knowledge of the diagnosis on the patient.

Conservative (Watch and wait)

Follow-up of incidental meningiomas

Natural course of untreated meningiomas

Meningiomas have variable growth rates, and that the growth rates reduce or even cease after the tumors attain a certain size
The growth rate is variable and on many occasions is non- linear.
Hashiba et al (2009)-measured by volume (n70) followed for 3.3 years

62.9 % increased in size
15-25% per year

Factors associated with tumour growth

Older slower growth

Due to endocrine changes

Tumor growth rates increase as tumor volume increases
MRI hypointensity on T2-weighted images is associated with slowed tumor growth, and that MRI hyperintensity on T2-weighted images is associated significantly with faster tumor growth.
Meningiomas without calcification on imaging are more likely to progress than are calcified meningiomas

Radiological definition of tumour growth

An annual growth rate of > 1 cm3/year OR
Volume increases > 15%

Surgery

Principles of meningioma surgery

How do we start?	How do we get there?	What do we do when we arrive?
3 factors:	3 elements:	3 conditions:
Patient factors	Corridor	Controlling the space
Tumor factors	Craniotomy	Managing the time
Surgeon factors	Modifiers	Tempering the zeal