Meningioma Flashcards
1
Q
Where do meningiomas most commonly arise?
A
- arise from **ARACHNOID **layer of meninges
- commonly at sites of high density of arachnoid villi and associated arachnoid cap cells
- Most frequently noted at SUPRATENTORIAL sites of DURAL **REFLECTION **such as
- **cerebral convexity **20%
- **parafalcine/parasagittal **25%
- along** sphenoid wing **20%
- skull base (decreased surgical access)
- intraventricular and suprasella
- olfactory groove
- posterior fossa most commonly along the petrous bone
2
Q
Describe the WHO classification of meningiomas
A
In WHO classification
meningiomas are graded from grade 1 to 3 based on histological features (e.g. mitotic index), some histological subtypes (e.g. chordoid meningiomas and clear cell meningiomas) and molecular features
The WHO classification correlates with outcome so has a major bearing on treatment.
WHO grade 1 (benign)
WHO grade 2 (atypical but still benign)
WHO grade 3 (malignant)
3
Q
Explain the clinical significance of different pathological grades of meningioma
A
Grade correlates with clinical outcome and so affects treatment decisions
Higher grade = more likely to recur/progress
4
Q
Describe the common associations with meningioma
A
- Prolonged exogenous hormone use
- MEN1
- NF2
5
Q
What MRI sequences would be useful at determining disease extent of meningioma
A
T1
T2
T1 with gadolinium contrast
6
Q
What are the indications for treatment vs observation of meningioma
A
7
Q
Discuss radiotherapy in definitive setting for meningioma
A
8
Q
Discuss radiotherapy in adjuvant setting for meningioma
A
9
Q
Discuss radiotherapy for meningioma in recurrent setting
A
10
Q
What are indications for SRT vs fractionated RT
A
11
Q
What are indications for particle therapy for meningioma
A
12
Q
Discuss the circumstances for maximal safe resection
A
13
Q
Describe situations where complete surgical resection is difficult
A
skull base
parasagittal
14
Q
What are systemic treatments used for meningiomas
A
15
Q
Describe potential long and short term side effects associated with RT
A
16
Q
Describe potential long and short term side effects associated with surgery
A
17
Q
Radiological appearance of meningioma on MRI
A
On MRI, extra axial dural based mass
T1: hypo intense or isointense to grey matter
T2: isointense or hyperintense
Post gadolinium contrast: intense homogeneous contrast enhancement
May show dural tail sign
18
Q
What is likelihood of local control with surgery alone for complete resection?
A
19
Q
What is the likelihood of local control with surgery alone with incomplete resection
A
20
Q
What is the likelihood of local control with definitive RT
A
21
Q
What is the likelihood of local control with adjuvant RT
A
22
Q
How is response after treatment assessed?
A
23
Q
Epidemiology of meningioma
A
- 2:1 F: M
but males more likely to have atypical or malignant meningioma
1: for anaplastic meningioma - incidence increases with age (esp >65)
- 30% of primary intracranial neoplasm
- most common benign intracranial neoplasm in adults
24
Q
Risk factors for meningioma
A
- older age (increase risk as age increases’
- median age 65years
- previous ionising radiation
- NF2 (life time risk of 75%)
- MEN1
- exogenous hormones e.g. HRT with oestrogen
- elevated BMI
- decreased physical activity
- increased height in women
- uterine fibroids
- High dose Cyproterone (>25mg/day)
25
Relative frequencies of the different grades of meningioma?
1/2/3
80%/18%/2%
26
What are pathological characteristics of grade 1 meningioma
Less than 4 mitoses/10HPF
PSAMMOMA bodies
Cellular whorls
Calcifications
27
What is the rate of recurrence of grade 1 Meningioma after GTR
7-25% reccurence rate
(So 5 year local control approx 90% after GTR)
28
What is the rate of recurrence of Gr2 meningioma after GTR
29-52%
(so 5year LC 50-60%)
29
What is the rate of recurrence of grade3 meningioma after GTR
50-94%
(so 5year LC 10-40%)
30
What is the system used to grade extent of resection in meningioma
Simpson system
31
On imaging, what features may indicate a higher grade of meningioma?
On MRI:
- Frank invasion of brain parenchyma
- absence of CSF-isointense cleft around tumour margin
- intra tumour cystic or necrotic change
- extension of tumour through skull base
- low apparent diffusion coefficient values
- elevated relative cerebral blood volume on perfusion weighted mri
32
What are the WHO grade criteria for gr3 meningioma (anaplastic)?
≥20 mitotic figures/HPF
carcinoma- , melanoma- , or sarcoma- like histology
TERT promoter mutation
homozygous deletion of CDKN2A or CDKN2B
33
Clinical presentation of meningioma
- asymptomatic, incidental finding on imaging
- Headache
- seizures in 30%, assoc with non skull base location
34
What are the WHO grade criteria for gr2 meningioma?
increased mitotic activity (≥4 per 10 HPF), OR
brain invasion (tongue-like protrusions), OR
chordoid or clear cell histological subtype
OR at least 3 of the following:
1)Increased cellularity,
2)Small cells with high N:C ratios,
3)Sheet-like growth (patternless growth),
4)Spontaneous necrosis,
5) Prominent nucleoli.
35
what molecular changes are associated with worse prognosis in meningioma?
- TERT promoter mutation: grade 3
- homozygous deletion of CDKN2A/B: grade 3
- H3K27me3 loss of nuclear expression: worse prognosis
36
What are the differential diagnoses of meningioma?
Malignant:
- solitary fibrous tumour
- dural metastasis
- lymphoma
- gliosarcoma
- plasmacytoma
- chondrosarcoma (base of skull loc)
- chordoma (base of skull loc)
Benign:
- pituitary macroadenoma if in sellar region
- craniopharyngioma if in sellar region
- Acoustic neuroma if in CPA
- sarcoidosis
- granulomatosis with polyangiits
37
Work up of meningioma- Hx features
- Neurological sx?
- Hx of prior radiation exposure
-Famhx of NF2 or MEN1
38
Work up of meningioma- Physical
- may have neurological deficit in keeping with location of tumour e.g. visual field changes, weakness
- may have normal exam
- Occasionally, convexity tumors associated with prominent hyperostosis or direct bony extension may produce a palpable bulge on the skull.
- Physical stigmata of NF2
39
Work up- labs
CMP and FBC; as these are appropriate for workup for surgery and findings like anaemia or hypercalcemia may prompt additional testing for systemic malignancy or multiple myeloma
CSF not indicated
40
Work up - Imaging
MRI with contrast
CT- to define adjacent hyperostosis or calcification
Routine cancer staging not indicated if no hx of cancer and typical neuroimaging findings
41
What proportion of meningioma are spinal location?
- Spinal location accounts for 10% of all meningioma
42
How does the F:M ratio change in meningioma
- by location spine vs brain
- grade
- age range
- radiation induced
Spinal location: F:M ratio even higher, 4-9:1
Grade: males slightly more common for atypical or anaplastic
Age range: F:M predominance highest in the middle aged adult years, absent in childhood
Radiation induced: no female predominance
43
Radiologic appearance of meningioma on CT
On CT:
Well defined extraxial mass which displaces brain
Smooth contour
May be multilobulated or calcified
May be hyper dense compared with cortex due to hypercellularity
44
What gene is affected in NF2-related schwannomatosis?
- Mutations in the NF2 MERLIN tumour suppressor gene on Chr 22
- Autosomal dominant inheritance
45
What is the risk of development of meningioma development in NF2 and what type of meningiomas are more likely to be seen?
- approx 50% of patients with NF2 have meningioma, life time risk up to 75%
- incidence increases with age as in non NF2 individuals
- tend to develop meningioma at an earlier age than those with sporadic
- multiple meningioma often present
- Most meningiomas are intracranial, although intradural, extramedullary spinal meningiomas are also seen
- more frequently atypical or anaplastic compared with sporadic tumors
46
What evidence supports the theory that hormonal factors may have a role in the development of meningiomas?
The incidence of meningioma is higher in postpubertal females compared with males
●The female-to-male ratio is highest during the peak reproductive years and decreases in older adults
●Progesterone and androgen receptors are present in approximately two-thirds of cases, while estrogen receptors have been identified in approximately 10 percent of cases
A meta-analysis of six prospective case-control studies that included over 1600 meningioma cases found that ever-use of hormone therapy was associated with a small but statistically significant increase in the risk of meningioma (relative risk [RR] 1.35, 95% CI 1.2-1.5).
In studies that distinguished between estrogen-only versus combined estrogen-progestin hormone therapy, estrogen, but *not* combined therapy, was associated with increased risk (RR 1.31). This is equivalent to an approximate absolute excess risk of 2 per 10,000 users over five years.
47
What cell does meningioma arise from
Meningiomas are thought to arise from *meningocytes* or *arachnoid cap cells*, which themselves arise from pluripotent mesenchymal progenitor cells, which accounts for the unusual location of primary extradural tumours
48
What are the two main forms meningiomas have on macroscopic appearance on imaging?
globose: rounded, well defined dural masses, likened to the appearance of a fried egg seen in profile (the most common presentation)
en plaque: extensive regions of dural thickening
49
Macroscopic appearance of meningioma:
Macro appearance reflects various histologies encountered, ranging from very soft to extremely firm in fibrous or calcified tumours.
usually light tan in colouring, although again this will depend on histological subtypes.
Grossly rubbery/firm
Usually well circumscribed, attached to dura, can be lobulated, separates easily from brain (separated by arachnoid plane)
50
Why is MRI the best imaging modality for meningioma?
Meningiomas are best imaged with MRI with contrast as this most accurately delineates the tumour, presence of intra- and trans-osseous extension and relationship to the underlying brain.
51
What are some specific reasons CT can be useful in imaging meningioma?
useful if:
- bony anatomy is required (e.g. at the base of skull)
- when patients cannot have MRI,
- when the meningioma is entirely ossified/calcified ( burnt-out meningioma).
52
What are the classic microscopic features of Meningioma?
- Oval nuclei with delicate chromatin
- Frequent intranuclei pseudo inclusions
- Syncytial tumour cells with abundant eosinophilic cytoplasm
- Numerous whorls
- Occasional psammoma bodies
- May show MAIN (mitosis, nuclear atypic, brain invasion, necrosis) if higher grade
53
What is the IHC staining of meningioma?
Somatostatin receptor 2A +
EMA+
Vimentin +
PR+
S100+
Ki67 varies with grade
54
What are subtypes of Grade I meningioma?
Meningothelial
Fibrous
Transitional
Psammomatous
Angiomatous
Microcystic
Secretory
Lymphoplasmacyte-rich
Metaplastic
MFT SLM PAM
55
What are subtypes of grade II meningioma?
ACC
Atypical
Chordoid
Clear cell
56
What are subtypes of grade III meningioma?
RAP
Papillary
Anaplastic
Rhabdoid
57
What molecular genetic changes are seen in meningioma?
Loss of chromosome 22 (monosomy 22)
Mutation/deletion of NF2 seen in sporadic meningioma
TERT mutation, a/w higher risk of recurrence and shorter time to progression
58
What symptoms may be seen with a para sagittal meningioma?
Motor/sensory changes
59
What symptoms may be seen with a frontal meningioma?
Personality changes
Executive dysfunction
Disinhibition
Urinary incontinence
Broca's aphasia
60
What symptoms may be seen with a temporal meningioma?
Memory changes
Wernicke's aphasia (L)
Aprosody (R)
Olfactory symptoms, inc seizures
61
What symptoms may be seen with a cavernous sinus meningioma?
CN symptoms affecting CN III, IV, V1-2 and VI)
Decreased VA
Impaired EOM with resulting diplopia
Numbness
62
What symptoms may be assoc with an occipital meningioma?
Visual field deficit
63
What symptoms may be a/w a cerebellopontine angle meningioma?
Unilateral deafness/decreased hearing
Facial numbness
Facial weakness
64
What symptoms may be a/w an optic nerve sheath meningioma?
Ipsilat decreased VA/blindness
Exophthalmos
Ipsilat pupillary dilation
non reactive to direct light but consensual contraction
65
What symptoms may be a/w a sphenoid wing meningioma
Cranial neuropathy, seizure
(CN V, III, IV and VI)
66
What symptoms may be a/w a meningioma of the tentorium?
extra-axial compression with associated occipital, parietal, cerebellar symptoms
67
What symptoms may be a/w meningioma of foramen magnum?
Paraparesis
urinary/anal sphincter dysfunction
tongue atrophy +/- fasciculation
68
What symptoms may be a/w meningioma of spinal cord?
Back pain
Brown-sequard (hemi spinal cord) syndrome
69
What other aetiologies show a dural tail on CT imaging?
Lymphoma
Chloroma
Sarcoidosis
70
Work up- History component
Ask about possible symptoms
Risk factors- previous cranial RT, NF2 (or famhx)
71
Work up- Examination component
Full neurological examination
72
Work up- Investigations
CT head
MRI head
73
Characteristic imaging appearance of meningioma on CT
Well circumscribed, homogeneously contrast enhancing extra-axial lesion with dural tail
- Moderate-intense enhancement with contrast (always use IV contrast if possible)
- Dural tail present in 50% of meningioma = linear thickening and enhancement adjacent to extra-axial mass. Present in other tumour types
74
Characteristic imaging appearance of meningioma on MRI
T1 isointense to grey matter
T2 hyperintense to grey matter
Intensely inhancing with gadolinium contrast
oedema uncommon
75
Prognostic factors- patient
Age <45 = worse
PFS
76
Prognostic factors- tumour
Higher grade = worse
Proliferation index
Brain invasion
Tert mutation = grade 3
Homozygous deletion of CDKN2A/B: grade 3
H3K27me3 loss of nuclear expression: worse prognosis
77
Prognostic factors- Treatment
Extent of resection (GTR > STR > unresectable)
78
What are the management options for a grade I meningioma?
Observation
Surgery +- PORT
Definitive RT
79
What are the management options for a Grade II meningioma?
Surgery +- PORT
Definitive RT
80
What are the management options for a Grade III meningioma?
Surgery + PORT
Definitive RT
81
What type of meningiomas is observation appropriate for?
Yes:
- Incidental small, asymptomatic lesions
- G1 post GTR
Maybe:
-G1 post STR, or G2 post GTR
82
What type of surgery is the standard of care?
Maximal safe resection
83
What does the Simpson grading system do?
Describes extent of resection
Grades 1 (best) to 5 (worst)
Rule of thumb- recurrence risk = Simpson grade x 10
84
What is appropriate management of Gr I after GTR (Simpson grade 1-3)
Observation
85
What is appropriate management of GrII after GTR?
Observation vs adjuvant RT (59.4Gy/33# or 60GY/30#)
TROG ROAM study is currently underway to asses this in Gr II meningioma after GTR.
patients randomised to active observation or 60Gy/30#
86
What is appropriate management of GrIII after GTR?
Adj RT 59.4Gy/33# or 60GY/30#
87
What is appropriate management of Gr 1 after STR?
Observation
or
Adj RT 54Gy/30#
88
What is appropriate management of Gr II or III after STR?
Adj RT 59.4GY/33# or 60Gy/30#
89
What is appropriate management of an unresectable Gr I?
Definitive RT 54GY/30# or
SRS 14Gy/1#
90
What is the appropriate management of unresectable Gr II or III?
Def RT 59.4Gy/33# or 60Gy/30#
or
SRS 14GY/1#
91
What is appropriate management of recurrent Gr 1 meningioma?
Consider re-resection, then adj 54Gy/30# or SRS 14GY/1#
92
What is an appropriate dose fractionation for an optic nerve meningioma?
50.4Gy/28#
93
What is appropriate management of recurrent Gr II or III?
Re-resection is possible,
then adj RT 59.4Gy/33# or 60Gy/30#
94
What is an appropriate follow up schedule for Gr1-2?
MRI at 3, 6 and 12mo,
then 6-12mo for 5 years,
then every 1-3 years annually
(NCCN)
95
What is an appropriate follow up schedule for Gr 3?
MRI every 6-12 mo
96
What is the 5 year local control for Gr 3 after GTR vs surgery and adj RT?
GTR- 5yrLC 10-40%
Surgery + adj RT 5year LC 50-70%
97
What is the 5 year local control for a Gr 1 after STR? STR + adj RT?
STR alone- 5year LC 40-60%
STR + RT- 5year LC 95%
98
What is the 5year local control for a Gr2 after GTR alone vs GTR + adj RT?
GTR- 5year LC 50-60%
GTR + RT- 5 year LC 60-90%
99
What Simpson grades denote GTR
1-3
100
What is the natural history of meningioma?
Approximately 1 to 2 mm of growth annually for grade I meningiomas.
Most failures occur locally, and local progression can further aggravate associated neurologic symptoms.
Marginal failure around the meninges is possible, particularly with high-grade meningioma.
Approx 1-, 5-, and 10-year survival rates are 80%, 65%, and 58%, respectively
101
Do incidentally discovered meningiomas require aggressive intervention?
Incidentally appreciated meningiomas may not require additional intervention.
In at least one study, more than half of patients’ meningiomas demonstrated no growth at 5 years.
These patients may be followed with imaging at 3 to 6 months and then annually thereafter if no growth is appreciated.
102
What is the optimal first line management in the treatment of meningiomas?
Maximal safe surgical resection provides the greatest opportunity for minimizing recurrence rates. The extent of resection is graded according to the Simpson grading system.
103
Is there a role for chemotherapy in meningioma?
No
104
What dose of SRS should be used to treat meningioma and what are the outcomes?
Similar to brain metastases, SRS dose depends on the volume being treated and the dose to adjacent critical structures.
Mean doses generally have ranged from 16 to 24 Gy, depending on location, with >20 Gy associated with higher rates of LC.
Maximal dose for cavernous sinus meningiomas is 12 to 14 Gy, with doses >18 Gy associated with unacceptable CN toxicity.
Fractionated SRT with BED >50 Gy may decrease toxicity rates for patients in whom critical structures limit SRS dose.
Most SRS series report excellent LC, with 10-year rates ranging from >90% for WHO grade I to >60% for WHO grades II and III.
105
What is the role of RT in the management of WHO grade I meningiomas?
GTR (Simpson 1–3) is generally considered definitive, and patients may be followed with surveillance imaging.
However, with longer follow-up, recurrence rates as high as 20%, 40%, and 60% have been reported at 5, 10, and 15 years, likely reflecting modern imaging capabilities.
RT is typically reserved for salvage for these patients.
For those with STR (Simpson 4–5), recurrence rates of 40% at 5 years and 60% at 10 years can be reduced to those of GTR (approximately halved) with adjuvant RT doses >50.4 Gy.
106
What is the role of RT in the management of WHO grade II meningiomas?
Adjuvant RT is generally recommended after GTR and strongly recommended after STR.
Adjuvant RT after GTR of a WHO grade II meningioma is 54 Gy per RTOG 0539.
After STR of a WHO grade II, adjuvant RT to 59.4 Gy/33 fx or 60 Gy/30 fx is recommended to minimize risk of LR based on multiple retrospective series.
Without RT, LR rates of up to 60% at 5 years and CSS of only 70% at 10 years have been observed.
Following GTR (Simpson 1–2), 5-year PFS is roughly doubled, from approximately 40% to 80% with adjuvant RT.
Following STR, adjuvant RT is strongly recommended due to high recurrence rates.
107
Can RT margins be reduced in patients with WHO grade II meningioma treated with IMRT?
Although RTOG 0539 used at least a 1-cm CTV expansion for WHO grade II meningiomas, retrospective data suggest a 5-mm CTV and a 3-mm PTV may be used without undue risk of LR.
108
What is the role of RT in the management of WHO grade III meningiomas?
Adjuvant RT is necessary regardless of resection extent. WHO grade III meningiomas are relatively rare, with less than 300 cases per year in the United States. As such, decisive data are lacking, although it is clear that OS is relatively poor with a generally accepted mean of >3 years.
A minimum dose of 60 Gy is recommended.
109
OS for atypical vs anaplastic meningioma?
atypical- 12yrs
Anaplastic - 3yrs
110
At what size of meningioma should surgery be considered if accessible?
30mm or larger
111
What features are slow growth rates a/w?
Older age
calcifications
112
What are typical SRS doses for meningioma?
12-16Gy
50% IDL at tumour margin
Include dural tail
113
Describe pre-sim, and sim aspects of meningioma treatment
Pre-sim:
- MDM discussion
- Ophthalmology, audiometry, endocrinology review
Sim:
- Position: supine, arms at sides and shoulders as low as possible
- Immobilisation: thermoplastic mask
- Markers (wire/bolus): no
- Planning CT: 2mm CT scan with IV contrast from vertex to neck
- Fusion: pre-op and post-op MRI T1 sequence
114
Describe target volumes for VMAT plan
GTV =
gross disease (definitive) or residual disease on post op MRI T1 sequence with contrast
CTV=
GTV + 1cm along dual tail for Gr 2/3
+ 0.5cm along dural tail for Gr1
5mm into brain
clipped at anatomical boundaries
PTV = CTV + 3-5mm
115
Describe target volume for SRS plan
GTV = gross disease on T1 plus contrast
CTV = GTV + 3mm along dural tail
PTV = CTV + 1mm
116
Describe plan review for VMAT plan
Target coverage- PTV D98>95%
Minimise hot spots PTV <107%, ensure no hot spots outside of PTV or in OAR
Review low dose wash, ensure reasonable distributed around the PTV
Review OAR DVH
Brain: Max<60Gy
Spinal cord DMax <45Gy
Brainstem/optic nerve/chiasm Dmax<54Gy
Temporal lobe ALARA
Cochlear Dmean <45Gy
Lens Dmax <8Gy
Retina Dmax <45Gy
Lacrimal gland Dmean <30Gy
117
Describe treatment verification for VMAT vs SRS technique
VMAT: Daily Kv imaging with 3mm tolerance
SRS: daily KV imaging, no tolerance
