Meningioma Flashcards
Where do meningiomas most commonly arise?
- 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
Describe the WHO classification of meningiomas
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)
Explain the clinical significance of different pathological grades of meningioma
Grade correlates with clinical outcome and so affects treatment decisions
Higher grade = more likely to recur/progress
Describe the common associations with meningioma
- Prolonged exogenous hormone use
- MEN1
- NF2
What MRI sequences would be useful at determining disease extent of meningioma
T1
T2
T1 with gadolinium contrast
What are the indications for treatment vs observation of meningioma
Discuss radiotherapy in definitive setting for meningioma
Discuss radiotherapy in adjuvant setting for meningioma
Discuss radiotherapy for meningioma in recurrent setting
What are indications for SRT vs fractionated RT
What are indications for particle therapy for meningioma
Discuss the circumstances for maximal safe resection
Describe situations where complete surgical resection is difficult
skull base
parasagittal
What are systemic treatments used for meningiomas
Describe potential long and short term side effects associated with RT
Describe potential long and short term side effects associated with surgery
Radiological appearance of meningioma on MRI
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
What is likelihood of local control with surgery alone for complete resection?
What is the likelihood of local control with surgery alone with incomplete resection
What is the likelihood of local control with definitive RT
What is the likelihood of local control with adjuvant RT
How is response after treatment assessed?
Epidemiology of meningioma
- 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
Risk factors for meningioma
- 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)
Relative frequencies of the different grades of meningioma?
1/2/3
80%/18%/2%
What are pathological characteristics of grade 1 meningioma
Less than 4 mitoses/10HPF
PSAMMOMA bodies
Cellular whorls
Calcifications
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)
What is the rate of recurrence of Gr2 meningioma after GTR
29-52%
(so 5year LC 50-60%)
What is the rate of recurrence of grade3 meningioma after GTR
50-94%
(so 5year LC 10-40%)
What is the system used to grade extent of resection in meningioma
Simpson system
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
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
Clinical presentation of meningioma
- asymptomatic, incidental finding on imaging
- Headache
- seizures in 30%, assoc with non skull base location
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.
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
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
Work up of meningioma- Hx features
- Neurological sx?
- Hx of prior radiation exposure
-Famhx of NF2 or MEN1
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
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
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
What proportion of meningioma are spinal location?
- Spinal location accounts for 10% of all meningioma
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
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
What gene is affected in NF2-related schwannomatosis?
- Mutations in the NF2 MERLIN tumour suppressor gene on Chr 22
- Autosomal dominant inheritance
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
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.