General
- Lack recurrent mutations like ST ependymomas
- Uses methylation profiling to form subgroups: PFA and PFB
- Global levels of histone H3 K27-trimethylation
- Other rare fusion
- C11orf95-RELA fusions (normal in ST ependymomas but can also occur in PF)
Definition
- Essential:
- Posterior fossa tumour with morphological and immunohistochemical features of ependymoma AND
- Absence of morphological features of subependymoma AND (for NOS lesions)
- Molecular group evaluation was indeterminate, generated no result, or was not feasible
Numbers
- Median age at presentation of 6 years
- Slightly more frequent in male patients (52-62%)
- 8% of all neuroepithelial neoplasms in children and adolescents (birth to 19 years) are ependymomas
- Higher incidence of ependymomas is reported in White people, including children with eastern European ancestry, than in the Black and Hispanic populations
Molecular pathology
- Copy-number alterations → altered gene expression
- Epigenetic alterations, including
- Aberrant DNA methylation patterns
- EZHIP overexpression
- Loss of H3 p.K28me3 (K27me3)
Pathology
Macroscopic
- Circumscribed tumours
- Tan-coloured and are soft or spongy, with a gritty consistency if calcified
Microscopic
- A, Perivascular pseudorosettes are characterized by tumour cells radially arranged around blood vessels with and intervening anucleate zone.
- B, True ependymal rosettes characterized by periluminal cuboidal or columnar cells without a basement membrane.
- C, CNS WHO grade 3 posterior fossa ependymoma showing plentiful mitotic activity but little nuclear pleomorphism.
- D, Microvascular proliferation typically characterized by multilayered endothelial cells.
- E, Palisading necrosis.
- F, A pseudopapillary pattern with finger-like projections lined by a single layer or multiple layers of cuboidal cells.
Location
- 4th ventricle including
- Floor
- Lateral aspect (cerebellar peduncles)
- Roof
- Cerebellopontine angle
Clinical features
- Mass effect on surrounding posterior fossa structures
- Cranial nerve deficits
- Obstructive hydrocephalus
- Headache
- Vomit
- Rapidly growing head circumference.
Radiology
- Homogeneous mass filling the fourth ventricle.
- Haemorrhages and punctate calcifications may be observed
- The presence of intratumoural cysts and necrosis can result in variable enhancement on gadolinium injection.
- Lateral extension of the tumour via the foramina of Luschka and extension through the foramen of Magendie into the cisterna magna
- Envelops the lower cranial nerves and the PICA
Molecular subtype
Features | ||
Age | Infants and young children 3yrs | Adolescents and young adults 30 years. |
Molecular pathology | Low global levels of histone H3 K27-trimethylation | High global levels of histone H3 K27-trimethylation |
EZHIP over-expression | HIST1H3C HIST1H3B H3F3A K27M substitution | |
CpG island methylator phenotype | Cilliognensis dysregulation | |
Radiology | Calcification Lesser contrast enhancement | Cyst formation Greater contrast enhancement |
Prognosis | Poorer | Better |
Location | 4th ventricle roof | 4th ventricle floor |
Investigation
- MRI Brain + Spine + C
- Leptomeningeal dissemination at presentation is less common than in medulloblastoma;
Management
Surgery
- Extent of surgical resection is a major determinant of outcome.
- Surgery technique
- A hockey stick incision to allow CPA approach and also a midline approach
Chemotherapy
- Does not prolong overall survival
- Used as an adjunct to RT
- Given pre-operatively: used to shrink tumour or reduce blood supply to tumour
- After chemo - 5-10% pt will get haematological malignancy
Radiotherapy
- Radiation sensitive
- Immediate postoperative irradiation as standard of care, rather than using chemotherapy to delay irradiation
- Pre irradiation chemotherapy
- Tumors that progress during chemotherapy do not respond as well to subsequent irradiation
- Combining chemotherapy and irradiation does not improve overall survival.
- Delayed radiation therapy (often due to attempting chemotherapy first) is associated with worse prognostic outcomes, especially in young children
- EBRT: Post surgical debulking:
- Better overall survival rates, up to 85% at five years, compared to earlier studies with up to 73% at five years.
- This may be partly attributable to the high rate of gross total resection (82%) and use of radiotherapy for the first time in children under three years.
Outcome
- No robust relationship between histological grade and prognosis for posterior fossa ependymomas
- In general (historical data)
- 5-year overall survival for ependymoma has ranged from 50 to 64%
- Howe 2023
- Adjuvant Photon therapy after surgery for young children (age <3 years), n=101
- 10 year over all survival 72.6%
- Tumour progression 34% with a median time 1.6 years
- Death 34%
- For the ones that survived 98% achieve high school diploma
- Ramaswamy 2016
- Molecular subgroup predict outcome
- Incomplete PFA resection have the worst outcome
- RT for residual PFA is ineffective
- PFB have a better prognosis
- Prognostic factors (Merchant 2002)
- The extent of surgical resection
- Age
- Tumour grade
- Pre irradiation chemotherapy
- Tumors that progress during chemotherapy do not respond as well to subsequent irradiation
- Combining chemotherapy and irradiation does not improve overall survival.
- Delayed radiation therapy (often due to attempting chemotherapy first) is associated with worse prognostic outcomes, especially in young children
- Status of chromosome 1q gain
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