CNS & pituitary tumors
Gliomas, glioneuronal tumors, and neuronal tumors
Ependymal tumors
Ependymoma
Resident / Fellow Advisory Board: Meaghan Morris, M.D., Ph.D.
Editorial Board Member: Maria Martinez-Lage, M.D.
Last author update: 24 January 2022
Last staff update: 19 December 2022
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PubMed Search: Ependymoma CNS
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Frozen section description | Frozen section images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: De Los Santos Y, Cai C. Ependymoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorependymoma.html. Accessed September 27th, 2023.
Definition / general
- Neuroepithelial tumor with ependymal differentiation that most commonly has ventricular involvement and arises in the cerebrum and spinal cord
Essential features
- Well circumscribed tumor of ependymal differentiated cells that occurs in the supratentorium, posterior fossa and spinal cord
- Bimodal age distribution of children and adults, occurring equally between genders
- Is classified and prognosticated by location, histology and molecular and methylation studies
- Supratentorial ependymomas can have ZFTA fusions or YAP1 fusions; posterior fossa ependymomas are split into posterior fossa group A (PFA) and posterior fossa group B (PFB) by methylation profile; spinal ependymomas can have MYCN amplification
ICD coding
- ICD-10:
- C71.0 - malignant neoplasm of cerebrum, except lobes and ventricles
- C71.1 - malignant neoplasm of frontal lobe
- C71.2 - malignant neoplasm of temporal lobe
- C71.3 - malignant neoplasm of parietal lobe
- C71.4 - malignant neoplasm of occipital lobe
- C71.5 - malignant neoplasm of cerebral ventricle
- C71.7 - malignant neoplasm of brain stem
- C71.9 - malignant neoplasm of brain, unspecified
- C72.9 - malignant neoplasm of central nervous system, unspecified
- D33.2 - benign neoplasm of brain, unspecified
Epidemiology
- Ependymal tumors comprise 1.9% of all primary CNS tumors and 6.9% of primary glial neoplasms, with incidence rates of approximately 0.4/100,000 in the US. (Neuro Oncol 2015;17:iv1)
- Bimodal age distribution:
- Incidence rate is highest in infants <1 year of age and decreases thereafter (Neuro Oncol 2015;17:iv1)
- Anaplastic ependymoma was highest in age groups 0 - 4 years followed by age 5 - 9 years and 10 - 14 years respectively before plateauing in adults (Neurooncol Pract 2020;7:549)
- Second peak is in the fourth decade and dominated by spinal cord tumors, which are typically easily excised with good prognosis (JAMA Oncol 2018;4:1254)
- Equal gender distribution
Sites
- Typically associated with ventricular lining in the spinal cord or cerebrum but can occur intraparenchymally / paraventricularly, particularly in supratentorial tumors
- Spinal ependymomas commonly in cervical and thoracic spine
- Posterior fossa ependymomas around fourth ventricle
- Reference: Childs Nerv Syst 2003;19:270, Crit Rev Oncol Hematol 2007;63:81
Pathophysiology
- Single cell sequencing across all major molecular ependymoma groups revealed hierarchical cellular populations, including undifferentiated neural stem cells, radial glia cells and more differentiated cells towards ependymal, astrocytic and neuronal lineages
- Proportion of undifferentiated or less differentiated cells correlates with poor prognosis and increased recurrence
- Authors suggest that aberrant radial glia-like cells are potential cells of origin for supratentorial ependymoma, with C11orf95-RELA fusions and neural stem cell-like cells the origin of posterior fossa ependymoma (Cancer Cell 2020;38:44)
Etiology
- Unknown
Clinical features
- Spinal cord ependymomas present with pain, weakness, sensory loss or radiculopathy, depending on level affected
- Intracerebral ependymomas present with obstructive hydrocephalic symptoms, as well as features of mass effect, neurologic deficits or seizures, depending on location
- Reference: Pediatr Neurosurg 2019;54:98
Diagnosis
- Diagnosis is made by integrating histologic features, location and molecular findings (Neuro Oncol 2021;23:1231)
Radiology description
- Commonly discrete, well circumscribed mass with uniform contrast enhancement
- Hyperdense on computed tomography and hyperintense on magnetic resonance imaging
- Reference: Childs Nerv Syst 2009;25:1203
Radiology images
Contributed by Chunyu Cai, M.D., Ph.D.
MRI cervical spine ependymoma
MRI posterior fossa ependymoma
MRI supratentorial ependymoma
Images hosted on other servers:
MRI: ependymoma of fourth ventricle
Prognostic factors
- Spinal ependymomas with good prognosis in both children and adults secondary to location and ease of total gross resection
- Spinal ependymoma with MYCN amplification is exception, with poor prognosis
- Intracranial ependymomas have variable prognosis but overall are worse than spinal ependymomas and can have cerebrospinal fluid metastases
- Supratentorial ependymomas have better survival rates than posterior fossa ependymomas
- Supratentorial ependymomas with ZFTA-RELA fusions have worse prognosis
- Supratentorial ependymomas with YAP1 fusions have good prognosis
- Of posterior fossa ependymomas, posterior fossa group A has a worse prognosis than posterior fossa group B
- Gain of 1q predicts poor outcome and progression in posterior fossa ependymomas (Brain Pathol 2020;30:863)
- Complete resection is predictor of good prognosis in anaplastic ependymoma and ependymoma, NOS (Neurooncol Pract 2020;7:549)
Case reports
- 26 year old woman with neck pain (Cureus 2020;12:e7981)
- 28 year old man with incidental cerebellopontine angle mass (Medicine (Baltimore) 2019;98:e15019)
- 37 year old man with cervicomedullary mass (Asian J Neurosurg 2020;15:190)
- 44 year old woman with extramedullary lumbar spine mass (Yeungnam Univ J Med 2020;37:128)
Treatment
- Gross total resection if possible, with or without adjuvant radiotherapy
Gross description
- Gray-red tumors with or without cystic degeneration, hemorrhage or necrosis
- Intracranial tumors are well circumscribed
- Ependymomas of fourth ventricle are typically exophytic
Gross images
Images hosted on other servers:
Arising from floor of fourth ventricle
Frozen section description
- Cellular tumor with sharp border with brain parenchyma
- Perivascular pseudorosettes, true ependymal rosettes and lumina (J Neurosurg Spine 2018;30:133)
Frozen section images
Contributed by Chunyu Cai, M.D., Ph.D.
Fibrillary perivascular pseudorosette
Microscopic (histologic) description
- Cellular tumor with typically sharply circumscribed borders, may be infiltrative
- Monomorphic round to oval cells with speckled chromatin
- Perivascular pseudorosettes, true ependymal rosettes, lumina and fibrillar areas
- May see gemistocyte-like cells and hypercellular nodules, particularly in posterior fossa tumors
- Can have nonpalisading necrosis, areas of cystic or myxoid degeneration, calcifications, degenerative atypia, neuronal differentiation and rarely metaplastic elements
- Morphologic subtypes have no clinicopathological significance and include papillary, clear cell and tanycytic
- Utility of histological grading is debated; the 2021 WHO still recommend assigning either WHO grade 2 or grade 3 to an ependymoma, according to its histopathological features as part of the integrated diagnosis
- Myxopapillary ependymoma are now assigned WHO grade 2 in the 2021 WHO CNS tumor classification
- Subependymoma remains a WHO grade 1 (Neuro Oncol 2021;23:1231)
Microscopic (histologic) images
Contributed by Chunyu Cai, M.D., Ph.D. and Maria Martinez-Lage, M.D.
Perivascular pseudorosettes
Ependymal rosettes
True ependymal rosettes
Ependymoma canal
GFAP IHC
EMA IHC
MAP2 IHC
H3K27me IHC PFB
Contributed by Eman Abdelzaher, M.D., Ph.D.
Tanycytic ependymoma
H&E
EMA showing dot-like and ring-like positivity
Virtual slides
Images hosted on other servers:
Ependymoma
Cytology description
- Spindle shaped cells with oval to elongated nuclei and delicate fibrillary cytoplasm with occasional intracytoplasmic lumina, which can be arranged around blood vessels
- Occasional nuclear grooves and inclusions can be seen (J Pathol Transl Med 2019;53:104)
Cytology images
Contributed by Chunyu Cai, M.D., Ph.D.
Perivascular pseudorosette
Fibrillary cytoplasm
Positive stains
- Positive for S100, GFAP, vimentin
- Perinuclear dot-like pattern of EMA and D2-40 staining
- CD56 staining in lumina and tumor cells
- Variable membranous or dot-like staining for CD99
- Can have focal staining for keratin (CAM 5.2) and synaptophysin
- L1CAM can be positive in some supratentorial ependymomas but mostly is seen in RELA fusion tumors (Am J Surg Pathol 2019;43:56)
- In posterior fossa ependymomas, decreased expression of H3K27me3 is seen in posterior fossa group A, which has a worse prognosis (Acta Neuropathol 2017;134:705)
Negative stains
- Negative for neuronal markers (NeuN, chromogranin), Olig2 and IDH1
- Negative for reticulin
Electron microscopy description
- Features of ependymal cells:
- Cilia with a 9+2 microtubular pattern
- Blepharoblasts and microvilli of the lumina
- Zipper-like junctional complexes of lateral aspect
- Lack of basement membrane
- Reference: CNS Oncol 2014;3:49
Molecular / cytogenetics description
- Molecular groups based on fusion and methylation profiling (Cancer Cell 2015;27:728):
- Supratentorial ependymoma, ZFTA fusion positive (formerly C11orf95-RELA fusion tumors), comprises 60% of supratentoral ependymomas and portends a poor prognosis
- Supratentorial ependymoma, YAP1 fusion positive, has a better prognosis
- Posterior fossa ependymoma, group A
- Posterior fossa ependymoma, group B
- Spinal ependymomas with NF2 mutations
- Spinal ependymoma, MYCN amplified
- Molecular characterization of histopathological ependymoma variants (Acta Neuropathol 2020;139:305)
- Tanycytic ependymomas were mostly located in spinal cord; DNA methylation match to spinal or myxopapillary ependymoma
- Clear cell ependymomas were mostly supratentorial; DNA methylation match to RELA fusion positive ependymomas
- Papillary ependymomas match to posterior fossa group B or myxopapillary ependymoma
Videos
Ependymal tumors by Dr. Rodriguez
Sample pathology report
- Brain, right parietooccipital mass, resection:
- Ependymoma (WHO grade II) (see comment)
- Comment: The tumor is a histologically classic ependymoma with prominent perivascular pseudorosettes. It does not have features of anaplastic ependymoma (WHO grade III), such as high cellularity, high mitotic index or microvascular proliferation.
Differential diagnosis
- Infiltrating glioma:
- Astroblastoma:
- Astroblastic pseudorosette and IHC profile that resembles ependymoma
- Located almost exclusively in cerebral hemispheres
- Stout broad process that is strongly GFAP+
- MN1 rearrangement detectable by FISH (Cell 2016;164:1060, Brain Tumor Pathol 2019;36:112)
- Medulloblastoma:
- Posterior fossa ependymoma can radiographically and histologically resemble medulloblastoma, with monotonous cells and true rosettes
- Medulloblastoma is diffusely synaptophysin+
- Subtype specific markers: GAB1, YAP1, filamin A, beta catenin (nuclear)
- Schwannoma:
- Meningioma:
Additional references
Board review style question #1
A biopsy of an enhancing, well circumscribed mass located in the paraventricular white matter of the parietal lobe shows cells with oval nuclei and speckled chromatin forming perivascular pseudorosettes and true rosettes with lumina. Fluorescence in situ hybridization reveals a C11orf95-RELA fusion. What is the best diagnosis?
- Astrocytoma, IDH mutant
- Oligodendroglioma, IDH mutant and 1p / 19q codeleted
- Posterior fossa ependymoma
- Supratentorial ependymoma, YAP1 fusion positive
- Supratentorial ependymoma, ZFTA fusion positive
Board review style answer #1
Board review style question #2
Which immunohistochemical stain can help differentiate posterior fossa group A ependymomas from group B?
- EMA
- H3K27me3
- Ki67
- L1CAM
- S100
Board review style answer #2
B. H3K27me3. Posterior fossa group A ependymoma has decreased nuclear expression of H3K27me3, which predicts a worse prognosis.
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Reference: Ependymoma
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Reference: Ependymoma
