Meningioma

Lecture by-
Dr. Archana Tiwari
Associate Prof. & Head
 Introduction
• Definition
• Meningiomas, as defined by the 2016 World Health
Organization (WHO), are "a group of mostly benign, slow-
growing neoplasms that most likely derive from the
meningothelial cells of the arachnoid layer."
• These tumors fall into WHO grade I, with a low risk of
recurrence and aggressive behavior; grades II and III indicate
a greater likelihood of recurrence and aggressive behavior. [1]
• Meningioma comprises about one fourth (34%) of all
primary tumors of the central nervous system (CNS).
• It is the most common primary intracranial neoplasm and the
most diversified in histologic patterns among all primary
tumors of the CNS
• The peak incidence is in middle aged patients, and the
female:male ratio is approximately 2:1
• Meningiomas are generally benign (most common benign
Intracranial), slow growing tumours that may produce
neurological symptoms and signs due to their compression of
adjacent structures.
• They are, a tumour entity with vague clinical presentations, a
heterogeneous histological picture, and an inherent trend to
recur
• Known risk factors for recurrence include histological
malignancy grade, subtotal resection, young age, specific
subtypes, brain infiltration, and high proliferative rate
 Introduction ( Continued)

• Meningiomas are tumors of the meninges that can

compress adjacent brain tissue.
• Meningiomas are neoplasms thought to derive from
arachnoidal cap cells in the meningeal coverings of the spinal
cord and brain
• Symptoms depend on the tumor’s location.
• Diagnosis is by MRI with contrast agent, confirmed by
Histopathology.
• Treatment may include excision, stereotactic radiosurgery,
and sometimes radiation therapy.
• 3 grades exist based on WHO criteria:
• Most are slow growing WHO grade 1 (benign)
• 20 - 25% are WHO grade 2 (increased likelihood of
recurrence)
• 1 - 6% are WHO grade 3 (malignant with metastatic potential)
 Role of Pathologist
• Histopathological examination and grading of meningiomas
gives valuable prognostic information, although the method
is subject for interobserver variability.
• Much progress has been made in understanding the molecular
and genetic basis for meningioma tumorigenesis. In clinical
practice, however, the diagnosis is based on light microscopy
of routinely stained haematoxylin-eosin sections with criteria
given by World Health Organization (WHO)
 Epidemiology
Location
• Meningiomas, particularly those < 2 cm in diameter, are among the
most common intracranial tumors.
• Meningiomas are the only brain tumor more common among
women.
• These tumors tend to occur between ages 40 and 60 but can occur
during childhood.
• Meningiomas, which are usually benign, can develop wherever
there is dura, most commonly over the convexities near the venous
sinuses, along the base of the skull, and in the posterior fossa and
rarely within ventricles.
• Multiple meningiomas may develop.
• Meningiomas compress but do not invade brain parenchyma. They
can invade and distort adjacent bone.
 Key Points

• Meningiomas are tumors of the meninges that are usually

but not always benign.
• They typically occur between ages 40 and 60 and are more
common among women.
• Symptoms vary greatly depending on the location of the
tumor.
• Excise symptomatic or enlarging tumors; use stereotactic
radiosurgery if tumor remains after excision or cannot be
excised completely.
• Benign tumors of adults that arise from the meningothelial cells of
the arachnoid and are usually attached to the dura.

Site:
• Along any of the external surfaces of the brain

• Within the ventricular system, where they arise from the stromal
arachnoid cells of the choroid plexus

• Common sites of involvement include:

– The parasagittal aspect of the brain convexity
– Dura over the lateral convexity
– Wing of the sphenoid
– Olfactory groove
– Sella turcica
• Extra dural tumors: <1%
 Sinosal cavity: Most common
 Intaosseous and may involve scalp
 Parotid gland
 Skin
Risk Factors:
• Prior radiation therapy to the head and neck

Clinical Features:
• Patients present either with vague nonlocalizing symptoms or
with focal findings referable to compression of underlying
brain.

• Uncommon in children

• Generally show a moderate (3 : 2) female predominance

• Meningiomas often express a variety of hormone (e.g.,

progesterone) receptors and may grow more rapidly during
pregnancy, only to regress after delivery.
C/F depends upon location
  Base of skull  Foramen magnum
• Visual loss • Ipsilateral suboccipital pain
• Paresis that begins in the ipsilateral arm and
• Oculomotor palsies
progresses to the ipsilateral leg, then to the
• Exophthalmos contralateral leg and arm
• Sometimes Lhermitte sign
 Cerebral convexities • Cranial nerve deficits (eg, dysphagia, dysarthria,
nystagmus, diplopia, facial hypoesthesia)
• Focal seizures
 Olfactory groove
• Cognitive deficits • Anosmia
• Ultimately, signs of increased • Sometimes papilledema and visual loss
intracranial pressure  Parasagittal or falx
• Spastic paresis or sensory loss, usually
 Clivus and apical petrous bone beginning in the contralateral leg, but
occasionally bilateral
• Gait disturbance • Cognitive deficits
• Limb ataxia  Posterior fossa tentorial tumors that extend
• Deficits referable to the 5th, 7th, and 8th superiorly or inferiorly
cranial nerves • Hydrocephalus
barber chair phenomenon is the - an electric shock-like sensation that occurs on flexion of the
neck.
Pathogenesis:
• Loss of chromosome 22, especially the long arm (22q) most
common

• Deletions include the region of 22q12 that harbors the NF2 gene
which encodes the protein merlin

• Sporadic meningiomas 50% to 60% harbor mutations in the NF2

gene
 Most commonly seen in convexity tumors
 Eventually become higher grade
• Without NF2 mutations, the most common mutations occur in
TRAF7, KLF4, AKT1, and SMO
 Most involve the skull base
 Lower risk of malignant progression

• Higher-grade meningiomas:
 More often have chromosomal losses involving several
chromosomes, TERT-promoter mutations, and
homozygous CDKN2A gene deletions.
 Morphology:
Gross:
• Usually rubbery, rounded, or
bosselated dural masses that
compress underlying brain but
are easily separated from it

• May also grow en plaque, in

which the tumor spreads in a
sheetlike fashion along the
surface of the dura

•Hyperostotic changes in the adjacent bone

due to invasion but does not signify
malignancy
Note how this meningioma beneath the dura has compressed
the underlying cerebral hemisphere. Rarely, meningiomas
can be more aggressive and invade underlying cerebrum or
overlying bone.
• On gross examination, meningiomas may be attached to the
dura, though they do not arise from the dura per se.
• They are extra-axial tumors and most displace brain tissue
without invading it.
• Some meningiomas grow flat on the surface of the brain.
Meningiomas tend to infiltrate overlying bone, which is
thickened (hyperostosis).
• Lesions range from firm to finely gritty (sandlike)

Due to numerous
psammomatous
calcifications

The majority of meningiomas show loss of the entire chromosome 22 or 22q.

The latter contains the NF2 tumor suppressor gene, merlin.
Meningiomas, especially of the fibroblastic type, are one of the BT seen in BANF.
• Meningiomas arise from arachnoidal cells. Microscopically, they have a
variety of appearances on the basis of which they have been classified into
several histological types.
• Meningothelial meningiomas are composed of diffuse masses of arachnoidal-
like cells. In transitional meningiomas, tumor cells are arranged in whorls
with hyalinized and calcified centers that are called psammoma (sand)
bodies because they resemble tiny grains of sand.
• Fibroblastic meningiomas are composed of fascicles of fiber-like cells with
abundant interstitial collagen.
• Meningothelial, transitional, and fibroblastic are the most common
histological subtypes of meningioma but there are many more. Many
meningiomas are histologically mixed. The tumor cells are positive for
epithelial membrane protein. Some meningiomas express progesterone
receptors resulting in accelerated growth during pregnancy.
 CLASSIFICATION
• Meningiomas are subdivided in 15 histo- and
cytomorphological variants of which nine variants correspond
to WHO grade I, three variants correspond to WHO grade II,
while another three variants correspond to the malignant type
of WHO grade III meningiomas.
• The most common histomorphological subtypes are WHO
grade I meningothelial, fibrous and transitional
meningiomas
 Meningiomas
• Grow as well-defined dural-based masses
• Compress underlying brain but are easily separated from it.
• Extension into the overlying bone may be present.
• Different histologic patterns found in meningiomas:
– Syncytial- whorled clusters of cells that sit in tight groups without visible
cell membranes;
– Fibroblastic- with elongated cells and abundant collagen deposition
between them
– Transitional- which shares features of the syncytial and fibroblastic types
– Psammomatous- with numerous psammoma bodies
– Secretory- with PAS-positive intracytoplasmic droplets and intracellular
lumina by electron microscopy
– Microcystic- with a loose and spongy appearance.
Parasagittal multilobular meningioma attached to the dura with compression of
underlying brain
Meningioma with a whorled pattern of cell growth and psammoma bodies.
• Atypical meningiomas-
– Lesions with a higher rate of recurrence
– More aggressive local growth, and
– Possible need for therapy in addition to surgery
– Recognized by several histologic features including a higher mitotic rate
• Anaplastic (malignant) meningiomas
– Highly aggressive tumors that resemble a high-grade sarcoma
– presence of brain invasion is associated with increased risk of recurrence
• The overall prognosis of meningiomas is influenced by: the
– Size
– Location
– Surgical accessibility
– Histologic grade.
 Meningotheial meningioma (Grade I)
• Contain clusters of epithelioid
cells with fuzzy or
indiscernible cell membranes

• The cells have nuclei with

finely distributed chromatin
and inconspicuous nucleoli

• Whorl formation and

psammoma bodies are
infrequent
 Fibroblastic meningioma Grade (II)
• Contains intersecting fascicles of spindled cells and abundant
collagen deposition
 Transitional meningioma(Grade I)
• Mixed meningothelial and fibroblastic features, often
including many whorls (concentric wrapping of tumor cells
around one another)
 Psammomatous meningioma(Grade I)
• Predominance of psammoma bodies

• Psammoma bodies represent concentric rings of calcification

deposited over pre-existing whorls

• Intervening meningothelial
cells are hard to find.
 Angiomatous meningioma(Grade I)
• Features numerous blood vessels, which often constitue
greater proportion of tumor mass than do the intermixed
meningioma cells

• Also known as vascular meningioma

 Microcystic meningioma(Grade I)
• Characterized by cells with
thin elongated processes
encompassing microcysts
and creates a cobweb like
background.
 Lymphoplasmacyte rich
Secretory meningioma(Grade I) meningioma(Grade I)
Metaplastic meningioma(Grade II) Chordoid meningioma(Grade II)
Clear cell meningioma(Grade II)
 Atypical meningioma(Grade II)
Criteria:
– Increased mitotic activity > 4
mitosis/10hpf
– Brain invasion

Three of the following features:

i. Increased cellularity
ii. Small cells with increased N:
C ratio
iii. Prominent nucleoli
iv. Patternless or sheet like
growth
v. Spontaneous necrosis
 Papillary Meningioma(Grade III)
• The tumor cells are frequently
arranged in papillary structures
around blood vessels

• High cellularity and mitotic

activity with evidence of brain
invasion are common
 Rhabdoid meningioma(Grade III)
• Characterized by Rhabdoid
cells: eccentrically placed
vesicular nuclei, prominent
nucleoli, open chromatin
and eosinophillic globular/
fibrilar paranuclear
inclusions
 Anaplastic (malignant)
meningioma, Grade III
• Exhibits overtly malignant cytology (resembling that of
carcinoma, melanoma, or high-grade sarcoma) and/or
markedly elevated mitotic activity.

• Display marked nuclear and cellular pleomorphism, high

mitotic activity, and necrosis

• Account for 1/4th of meningiomas

• Mitosis> 20
mitosis/10hpf

• Sheet –like growth with

large epithelioid cells,
abundant cytoplasm and
prominent nucleoli.
 Others morphological variants

1. Oncocytic variant
2. Mucinous variant
3. Sclerosing variant
4. Whorling- sclerosing variant
5. Meningothelial rosettes
Retinoblastoma
• Most common primary intra-ocular malignancy in children

• Mutation of RB gene

• Can be Hereditary or Sporadic

 Morphology

• Intra-ocular tumor
• Variable size
• Creamy white with chalky
areas of calcification and
yellow necrotic areas
Microscopy:

• Proliferation of Small, round

cells with hyperchromatic
nuclei

• Flexner-Wintersteiner or
Homer Wright Rosettes

• Fleurettes

• Dystrophic calcification or
areas of hemorrhage
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