CNS tumor

Ependymal tumors

Ependymoma



Minor changes: 8 October 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Ependymoma [title] CNS

See also: Clear cellPapillaryTanycytic

Yanel De Los Santos, M.D.
Chunyu Cai, M.D., Ph.D.
Page views in 2020: 28,269
Page views in 2021 to date: 34,167
Cite this page: De Los Santos Y, Cai C. Ependymoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorependymoma.html. Accessed December 7th, 2021.
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
  • Comprises approximately 6.8% of primary CNS tumors, with incidence rates of approximately 0.4/100,000 in the U.S. (Neuro Oncol 2015;17:iv1)
  • Bimodal age distribution:
    • Incidence rate is highest in infants < 1 year of age and decreases thereafter; pediatric ependymomas occur intracranially (more commonly infratentorially than supratentorially), with worse prognosis compared with intracranial ependymomas in adults and those in the spinal cord (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
  • African American populations had lower incidence but had a 78% increased risk of death (Neurooncol Pract 2020;7:549)
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
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 cervical spine ependymoma

MRI posterior fossa ependymoma

MRI posterior fossa ependymoma

MRI supratentorial ependymoma

MRI supratentorial ependymoma



Images hosted on other servers:
Missing Image

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
  • 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 (Am J Surg Pathol 2019;43:56)
    • 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 (Neurooncol Pract 2020;7:549)
Case reports
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:
Missing Image

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.
Ependymoma frozen section

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
  • Grading (either grade 2 or 3) may be assigned on nonmolecularly defined ependymomas but its significance is disputed at this time
    • Molecular defined ependymomas are not graded
    • Myxopapillary ependymoma is 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.
Perivascular pseudorosettes HE 20x

Perivascular pseudorosettes

Ependymal rosettes

Ependymal rosettes

True rosettes

True rosettes

Ependymoma canal

Ependymoma canal


GFAP IHC

GFAP IHC

EMA IHC

EMA IHC

MAP2 IHC

MAP2 IHC

H3K27me IHC PFB

H3K27me IHC PFB

Virtual slides

Images hosted on other servers:

Ependymoma

Cytology description
  • Spindle shaped cells with nuclear grooves and inclusions / intracytoplasmic lumina around thin capillaries
  • Fibrillar areas and possible areas of nonpalisading necrosis (J Pathol Transl Med 2019;53:104)
Cytology images

Contributed by Chunyu Cai, M.D., Ph.D.
Perivascular pseudorosette

Perivascular pseudorosette

Cytology ependymoma

Fibrillary cytoplasm

Positive stains
Negative stains
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
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?

  1. Astrocytoma, IDH mutant
  2. Oligodendroglioma, IDH mutant and 1p / 19q codeleted
  3. Posterior fossa ependymoma
  4. Supratentorial ependymoma, YAP1 fusion positive
  5. Supratentorial ependymoma, ZFTA fusion positive
Board review style answer #1
E. Supratentorial ependymoma, ZFTA fusion positive

Comment Here

Reference: Ependymoma
Board review style question #2

Which immunohistochemical stain can help differentiate posterior fossa group A ependymomas from group B?

  1. EMA
  2. H3K27me3
  3. Ki67
  4. L1CAM
  5. S100
Board review style answer #2
B. H3K27me3. Posterior fossa group A ependymoma has decreased nuclear expression of H3K27me3, which predicts a worse prognosis.

Comment Here

Reference: Ependymoma
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