Meningioma and ependymoma.

1. Meningioma and Ependymoma
Dr Kiran Kumar BR

2. Meningioma
• Harvey Cushing first used the phrase
“meningioma” to describe tumors originating
predominately from the meningeal coverings
of the brain.
• Arise from arachnoidal cap cells.
• 85-90% supratentorial in location.

3. Epidemiology
• Meningiomas are the most frequently reported primary
intracranial neoplasm.
• Pediatric meningiomas are rare, but are more likely to
exhibit an aggressive clinical course.
• Meningiomas are most often diagnosed during the
sixth to seventh decades of life.
• Meningiomas occur more frequently in females, at a
ratio of 2 : 1.

4. Etiology
• Radiation exposure—stemming largely from
studies of atomic bomb fallout, but also from
studies of cranial and scalp irradiation.
• Recent data suggest lower dose exposure, such as
seen in dental x-rays, may also increase the risk of
meningioma development.
• Indeed, radiation-induced meningiomas are the
most commonly reported secondary neoplasm.

5. Molecular Biology
• Meningiomas occur more frequently in certain rare genetic conditions, such as type
2 neurofibromatosis (NF2).
• Mutation in the NF2 gene on chromosome 22q12 is the most common cytogenetic
alteration.
• Nearly all NF2 meningiomas have mutations of the NF2 gene, and most susceptible
families have alterations of the NF2 locus.
• Genetic losses of chromosomes 1p, 10, and 14q have been linked with malignant
progression or recurrence.
• Tumors with NF2, AKT1, SMO, PIK3CA, and TRAF7 mutations have been found
in approximately 80% of sporadic meningiomas
• Telomerase reverse transcriptase promoter (TERTp) mutations have been aligned
with shorter overall survival.

6. Macroscopic Microscopic
• Globose are rounded, well
defined dural masses, likened
to the appearance of a fried
egg seen in profile.
• En plaque meningiomas on
the other hand are extensive
regions of dural thickening.
• Arise from meningothelial
arachnoid cells
• Histological sub types include
Transitional
Fibroblastic
Syncytial
Psammomatous
Secretory
Microcytic
Papillary and rhabdoid :
have a propensity to recur

8. Prognosis
• Median patient survival :
• 10 years for WHO grade I meningioma
• 11.5 years for WHO grade II meningioma
• 2.7 years for WHO grade III meningioma
• 5-year survival rate:
81% for patients aged 21-64 years and 56% for
patients ≥ 65 years old

9. • For benign meningiomas, factors independently associated
with longer survival included:
female sex, Caucasian race, surgery, small tumor
size, no radiation treatment, skull base tumor.
• For malignant meningiomas, factors independently
associated with longer survival included:
Younger age at diagnosis, female sex, surgery, no
radiation Treatment.

10. Clinical Features
• Depends on size and
location of tumor:
– Partial seizures
– Headache
– Personality changes
– Neuropsychological
deficits

11. Imaging
• Contrast-enhanced MRI is the imaging modality of choice for
meningiomas.
• Biologic imaging has been evaluated as an imaging modality
for meningioma and, although still considered experimental,
may ultimately prove useful in determination of grade, in
tumor delineation for radiation treatment planning, and for
differentiation of recurrence from treatment-related imaging
findings.
• Current limitations of biologic imaging include lack of
prospective data.
• Based on recent data, especially for skull-base locations,
Gallium tetraxentan octreotate (Ga-DOTATATE) positron
emission tomography (PET) imaging has been accepted as a
standard in Europe, especially to aid radiotherapy treatment
planning.

12. CECT
Buckling of white matter
Dural tail enhancement

13. Dural tail
Cisterns are widened Dural tail enhancement
MRI:POST CONTRAST

14. Primary Therapy
Benign Histology (WHO Grade I)
• Surgery is a mainstay in the management of
meningioma.
• It provides tissue for histologic typing and
grading.
• Postoperative radiotherapy. Adjuvant
radiotherapy is not recommended following
gross total resection of a newly diagnosed
grade I meningioma.

17. RT OVERVIEW

18. • For patients with symptomatic meningioma, or with asymptomatic
progressively enlarging tumors, complete surgical resection
recommended, where possible
• Alternative options include
Partial surgical resection plus radiation therapy
Radiation therapy
• For patients with inoperable or recurrent meningioma after surgery
or radiation therapy, medical therapies may be tried but have
limited and inconsistent evidence of efficacy

19. Selecting treatment modality
• Meningioma treatment approach treatment of asymptomatic meningioma
 For lesions < 3 cm (long axis), options include
• Observation
• Surgery for tumor with potential neurologic consequences if
accessible, followed by radiation therapy for world health
organization (WHO) grade III tumor or for subtotal resection of
WHO grade II tumor
• Radiotherapy for tumor with potential for neurologic consequences
 For lesions > 3 cm, options include
• Surgery if tumor is accessible followed by radiotherapy if tumor is
WHO grade III, and consider radiotherapy if resection is
incomplete and tumor is WHO grade I or II
• Observation

20. • Treatment of symptomatic meningioma
 For lesions < 3 cm, options include
Surgery if tumor is accessible, followed by radiotherapy for
WHO grade III tumors
Radiotherapy
 For lesions > 3 cm, options include
Surgery if tumor is accessible, followed by radiotherapy for
WHO grade III tumors, and consider radiotherapy for
incomplete resection of WHO grade I or II tumors
Radiotherapy

21. Radiotherapy

22. Overview
• Conventional radiation therapy
• Stereotactic radiosurgery
• Fractionated stereotactic radiosurgery

23. Indications
• Primary treatment for inoperable meningioma or for patients for
where surgery would be inappropriate.
follow-up treatment for patients with incomplete resection
of meningioma
• Complete tumor eradication not possible but tumor shrinkage
reported
• Treatment to dose of 54 Gy for Grade I and 60 Gy for Grade II-
III.

24. Conventional
• Conventional radiation therapy used to treat incompletely
resected meningioma, or treat patients for whom surgery is
inappropriate
• Addition of radiation therapy to partial resection may not
improve overall survival but may reduce tumor
progression in patients with WHO Grade I cerebral
meningioma.
5-year progression-free survival 91% for partial tumor resection plus
radiation therapy vs. 38% for partial tumor resection alone (p = 0.0005)
77% for total tumor resection vs. 52% for partial tumor resection
with or without radiation therapy (p = 0.02)
65% overall

25. • Whole-brain irradiation is administered through parallel-
opposed lateral portals. The inferior field border should be
inferior to the cribriform plate, the middle cranial fossa, and
the foramen magnum, all of which should be
distinguishable on simulation or portal localization
radiographs.
• The safety margin depends on penumbra width, head
fixation, and anatomic factors but should be at least 1 cm,
even under optimal conditions.
• A special problem arises anteriorly because sparing of the
ocular lenses and lacrimal glands may require blocking with
margins <5 mm at the cribriform plate.

26. • The anterior border of the field should be approximately 3
cm posterior to the ipsilateral eyelid for the diverging
beam to exclude the contralateral lens. However, this
results in only approximately 40% of the prescribed dose
to the posterior eye.
• A better alternative is to angle the beam approximately 3
degrees or more (100- or 80-cm source-to-axis distance
midline, but also field size dependent) against the frontal
plane so that the anterior beam border traverses posterior to
the lenses (approximately 2 cm posterior to eyelid markers).
• Placing a radiopaque marker on both lateral canthi and
aligning the markers permits individualization in terms of
the couch angle.
• This arrangement provides full dose to the posterior eyes.
However, the eyelid-to-lens and eyelid-to-retina topography
is individually more constant than the canthus, and lateral
beam eye shielding is better individualized with the aid of
CT or MRI scans.

28. SRS
• Stereotactic radiosurgery (SRS) may be alternative to
external beam radiation in patients with recurrent or
partially resected meningiomas < 35 mm in diameter
• Contraindications to surgery due to comorbidities or tumor
location
• Skull base tumors of small or moderate size, for which
surgical resection carries greater risk
• Allows larger radiation doses to be delivered more
accurately and limits radiation exposure to surrounding
tissue.

30. Fractionated SRS
• Fractionated stereotactic radiation therapy spares normal
tissue sensitive to hypofractionation.
• Preferred treatment of optic nerve sheath meningioma.

31. (A)stereotactic radiosurgery as a salvage therapy for a patient
with recurrent meningioma,
(B)fractionated stereotactic radiotherapy as a definitive
therapy for a patient with unresectable tumor due to a high
risk of cranial nerve damage after a surgery and
(C)3-dimensional conformal radiotherapy as a postoperative
radiotherapy for a patient with residual tumor after surgical
resection.

33. Proton therapy reduces rates of acute toxicity, fatigue and quality of
life.
ProtonTherapy

34. Benefits of Proton Therapy
• Causes fewer short- and long-term side effects
• Proven to be effective in adults and
children
• Targets tumors and cancer cells with precision, reducing the
risk of damage to surrounding healthy tissue and organs
• Reduces the likelihood of secondary
tumors caused by treatment
• Treats recurrent tumors, even in patients who have already
received radiation
• Improves quality of life during and after treatment

35. Treatment overview

36. Ependymoma

37. Introduction
• Ependymomas, which are glial tumors, arising from the
ependymal cells of the nervous system.
• The mean age at presentation is 30 to 39 years.
• These tumors are more common in adults than in children and
in males than in females.
• The median duration of symptoms before presentation is 2 to
4 years.
• Pain is the most common presenting symptom.

38. • Two-thirds occur in the lumbosacral region
and 40% arise from the filum terminale.
• Because of the propensity of these tumors to
seed the craniospinal axis(11%) CSF
evaluation and craniospinal MRI are strongly
recommended at time of diagnosis to
determine disease extent.

39. Epidemiology
• These tumors account for 1.8% of all primary CNS tumors.
• In children (0–19 y of age), ependymal tumors are
proportionally more common and account for 5.2% of all
primary CNS tumors.
• World Health Organization (WHO) classification of CNS
tumors into distinct entities and histological variants.
• The WHO classification also comprises a histological grading
into 3 distinct grades of malignancy: WHO grades I, II, and
III.

40. Biology
Bailey described 4 types
Myxopapillary
Subependymoma
• Ependymoma-
papillary ependymoma
clear cell ependymoma
tanycytic ependymoma
RELA fusion-positive (a new entity in 2016 update)
Anaplastic ependymoma(Grade III)

41. Pathology
• Ependymomas arise from ependymal cells and typically occur in the
central canal of the spinal cord, the filum terminale, and the white
matter adjacent to a ventricular surface.
• They are either low-grade tumors or anaplastic tumors, the latter
being more likely to disseminate via the CSF.
• Myxopapillary ependymomas are low-grade tumors that typically
occur in the lumbosacral region (filum terminale), are well
differentiated, and are often encapsulated but can seed the CSF,
typically with “drop metastases” in the thecal sac.
• Myxopapillary ependymomas often progress slowly and cause
milder-thanexpected neurological deficits for their size; however,
there are reports of CSF dissemination at diagnosis.

42. Immunohistochemistry
glial fibrillary acid protein (GFAP)
almost always positive in the cytoplasmic process around the
perivascular pseudorosettes
epithelial membrane antigen (EMA)
positive
S100: positive
vimentin: positive

43. Macroscopic appearance
• Macroscopically, ependymomas tend to be well defined
lobulated grey or tan-colored soft and frond-like tumors which
are moderately cellular. They may have focal areas of
calcification.
Microscopic appearance
• Microscopically, these tumors are characterized by well-
differentiated cells. Characteristic features include ependymal
rosettes, which are uncommon but pathognomonic and
perivascular pseudorosettes which are far more common and
seen in most of ependymomas.

44. Prognostic Factors
Factors prognostic for a favorable outcome include
• patient age younger than 40 years,
• tumors with a lumbosacral location,
• myxopapillary histological findings,
• WHO grade I classification,
• tumors amenable to GTR or STR, and
• good preoperative function of the patient.

45. Clinical Feautures
• Clinical presentation can vary according to location.
• Initial presentation with signs and symptoms of raised
intracranial pressure is common, particularly with tumors in
the fourth ventricle.
• Other posterior fossa symptoms including ataxia are also
encountered .
• Supratentorial ependymomas may also present with seizures or
focal neurological deficits

46. Imaging
• MRI with contrast enhancement is the modality of choice for
diagnosing ependymal tumors.
• MR spectroscopy reveals elevated choline and reduced N-
acetylaspartate levels.
• Perfusion MRI may display elevated cerebral blood volume
values and have some prognostic value.
• Spinal MRI- Cyst formation and T2 hypointensity of the cyst
wall due to blood products (“hemosiderin cap”) are
suggestive of ependymoma.

47. MRI
• T1
– isointense to hypointense relative to white matter
• T2
– hyperintense to white matter
– more reliable in differentiating tumor margins
• T2* foci of blooming from hemorrhage or calcification
• T1 C+ (Gd)
– enhancement present but heterogeneous
– enhancement with gadolinium is useful in differentiating tumor
from adjacent vasogenic edema and normal brain parenchyma

48. • MRI Brain a) Axial T1 post-contrast; b) Axial T2 FSE; c) Sagittal T1 with contrast; d) Axial ADC map.
A large mass predominantly filling and expanding the fourth ventricle with extension of the lesion
through the foramen of Luschka and Magendie. The lesion was low to isointense on T1 and
hyperintense on T2 weighted images. There was no restricted diffusion.

49. MRI Cervical Spine: a) Axial T1 post-contrast at the level of the upper
cervical spine; b) Sagittal T1 post-contrast; c) Sagittal T2 FSE.
61-year-old male with history of bilateral vestibular schwanomas and a
heterogeneously enhancing mass within the upper cervical cord centrally with
surrounding edema. Constellation of findings is consistent with
Neurofibromatosis type II and the spinal lesion is a presumed spinal
ependymoma.

52. Treatment
• Maximal surgical resection, including second
surgery if necessary, is the initial treatment for
ependymoma.

58. • Spinal myxopapillary ependymomas (WHO
grade I), where MR evidence of neuraxis
spread can be treated with focal radiotherapy,
rather than CSI.

59. Target Volume
The intent of CS-RT is to deliver a cancerocidal dose to the
primary tumor and any tumor cells distributed in the CSF or
tissue elsewhere in the nervous system.
The volume of irradiation thus includes:
Entire brain and its meningeal coverings with the
CSF Spinal cord and the leptomeninges with CSF
Lower border of the thecal sac.

60. Evidence-Based Treatment Summary
1. Maximal surgical resection should be performed when
feasible.
2. Postoperative radiotherapy is considered the standard, but
no prospective trials have validated its role.
3.CSI is used only in patients with disseminated disease.
4. The role of chemotherapy remains to be defined.

61. Thank you
Reference:
1.Perez and Brady principles of Radiation Oncology 7th Edition.
2.Gunderson and Teppers clinical radiation Oncology.
3.NCCN 2020.