Ependymoma

Ependymomas are glial cell tumors arising from CSF-producing ependymal cells lining the ventricular system Ventricular System The ventricular system is an extension of the subarachnoid space into the brain consisting of a series of interconnecting spaces and channels. Four chambers are filled with cerebrospinal fluid (CSF): the paired lateral ventricles, the unpaired 3rd ventricle, and the unpaired 4th ventricle. Ventricular System. Ependymomas most commonly occur within the posterior fossa in contact with the 4th ventricle, or within the intramedullary spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord. The clinical presentation of ependymomas varies depending on the location of the tumor. Magnetic resonance imaging is the imaging modality of choice, but histologic confirmation is required for diagnosis. The mainstay of treatment for intracranial ependymoma is surgical resection and adjuvant radiation therapy; young patients receive chemotherapy instead. Spinal cord ependymomas are treated with maximal surgical resection.

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Overview

Definition

Ependymomas are glial cell tumors in the CNS arising from ependymal cells.

  • Glial cells are supportive tissues within the brain and nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System.
  • Ependymal cells produce CSF.
  • May arise anywhere in the ventricular system Ventricular System The ventricular system is an extension of the subarachnoid space into the brain consisting of a series of interconnecting spaces and channels. Four chambers are filled with cerebrospinal fluid (CSF): the paired lateral ventricles, the unpaired 3rd ventricle, and the unpaired 4th ventricle. Ventricular System (intracranial ependymoma) or spinal canal (spinal ependymoma), but most commonly:
    • Children: the posterior fossa at the floor of the 4th ventricle 
    • Adults: lumbosacral spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord or filum terminale

Classification of nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System tumors

Table: Classification of nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System tumors
Categories Specific tumors
Neuroepithelial tumors in the CNS
  • Astrocytoma Astrocytoma Astrocytomas are neuroepithelial tumors that arise from astrocytes, which are star-shaped glial cells (supporting tissues of the CNS). Astrocytomas are a type of glioma. There are 4 grades of astrocytomas. Astrocytoma, including glioblastoma multiforme Glioblastoma multiforme Glioblastoma multiforme is a high-grade astrocytoma, an aggressive brain tumor arising from astrocytes, with an unknown cause and a poorly understood link to risk factors. There are two main types: primary, a more aggressive form seen more commonly in older patients, and secondary, developing from lower-grade astrocytomas and seen more commonly in younger patients. Glioblastoma Multiforme
  • Oligodendroglioma Oligodendroglioma Oligodendrogliomas are malignant CNS tumors arising from neural glial cell precursors. Oligodendrogliomas often arise in the frontal lobes of the brain and have a generally favorable prognosis when compared to other gliomas. Oligodendrogliomas are the 3rd most common CNS tumor. The most frequent presenting symptom is a seizure. Oligodendroglioma
  • Ependymoma and choroid-plexus tumor
  • Medulloblastoma Medulloblastoma Medulloblastomas are malignant primitive neuroectodermal tumors that arise in the posterior fossa in children. Medulloblastomas are the most common malignant brain tumors in children. Patients with medulloblastoma present with symptoms of increased intracranial pressure and cerebellar signs, which both evolve and worsen over weeks to a few months. Medulloblastoma (embryonal tumor)
Meningeal tumors
  • Meningioma Meningioma Meningiomas are slow-growing tumors that arise from the meninges of the brain and spinal cord. The vast majority are benign. These tumors commonly occur in individuals with a history of high doses of skull radiation, head trauma, and neurofibromatosis 2. Meningioma
  • Hemangioblastoma Hemangioblastoma Hemangioblastomas are vascular neoplasms of the CNS. Hemangioblastomas are rare and are often associated with von Hippel-Lindau disease (VHL). The most common presentation is a headache and, depending on the size and location of the tumor, patients may present with sensory deficits and motor weakness. Hemangioblastoma
Sellar-region tumors
  • Craniopharyngioma Craniopharyngioma Craniopharyngiomas are rare squamous epithelial tumors with a solid and/or cystic structure that arise from the remnants of Rathke's pouch along the pituitary stalk, in the suprasellar region. Craniopharyngiomas are histologically benign but tend to invade surrounding structures; thus, they should be treated as low-grade malignancies. Craniopharyngioma
  • Pituitary adenoma Pituitary adenoma Pituitary adenomas are tumors that develop within the anterior lobe of the pituitary gland. Non-functioning or non-secretory adenomas do not secrete hormones but can compress surrounding pituitary tissue, leading to hypopituitarism. Secretory adenomas secrete various hormones depending on the cell type from which they evolved, leading to hyperpituitarism. Pituitary Adenomas
  • Pinealoma/pinealoblastoma
Primary CNS lymphoma Primary CNS lymphoma
Metastasis to the brain (5x more common than primary brain tumors) Most commonly arising from:
  • Lung, breast, and renal cell carcinomas
  • Melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma
Peripheral tumors
  • Schwannoma Schwannoma Schwannomas (also known as neurilemmomas) are benign nerve sheath tumors in the peripheral nervous system (PNS), arising from Schwann cells that encase the peripheral nerves. Schwannomas are the most common tumors in the PNS. Schwannoma, including acoustic neuroma Acoustic neuroma Acoustic neuroma, also referred to as vestibular schwannoma, is a benign tumor arising from Schwann cells of the vestibular component of the cranial nerve VIII. Acoustic neuroma forms within the internal auditory meatus and extends into the cerebellopontine angle. Acoustic Neuroma
  • Neuroblastoma Neuroblastoma Neuroblastoma is a malignancy that arises from the neural crest cell derivatives along the sympathetic chain (neuroblasts) and is most commonly located in the adrenal medulla. The tumor often presents in childhood with a flank mass that crosses the midline. Neuroblastoma

Epidemiology

Intracranial ependymoma:

  • Incidence: 
    • < 6%–9% of primary tumors arising in the CNS
    • 30% of primary CNS neoplasms in children < 3 years old
    • In children, 90% of ependymomas are intracranial.
    • 3rd most common pediatric brain tumor (behind medulloblastoma and pilocytic astrocytoma)
  • Age: 
    • More common in children than adults
    • Median age at diagnosis: 4–5 years old
    • 25%–40% of patients are < 2 years old.
    • Intracranial ependymoma in adults usually occurs prior to age 40.
  • Sex: slight predominance in men
  • Location: most commonly occurs in the posterior fossa

Spinal ependymoma:

  • Incidence: 
    • Approximately 25% of primary spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord tumors
    • In adults, 75% of ependymomas are in the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord.
  • Age: 
    • More common in adults
    • Median age at diagnosis: 30–40 years of age 
  • Location: 
    • Approximately 50% occur in the lumbosacral cord or filum terminale.
    • Approximately 50% occur elsewhere in the cervical or thoracic spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord.

Etiology

  • No known cause of ependymoma
  • Clustering of the disease within families has been noted.
  • Increased incidence of spinal ependymoma in neurofibromatosis 2 ( NF2 NF2 Neurofibromatosis type 2 is a neurocutaneous disorder that can arise from mutations in the NF2 gene located in chromosome 22 and may be inherited in an autosomal dominant fashion or occur from de novo mutations. The main clinical features are bilateral vestibular schwannomas, intracranial/spinal meningioma, and intramedullary and extramedullary spinal tumors. Neurofibromatosis Type 2)

Pathophysiology

  • Arises from ependymal cells:
    • The cells line the cerebral ventricles and passageways in the brain and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord.
    • Derived from radial glial cells in the subventricular zone
  • Transformation from normal ependymal cells into neoplastic cells:
    • Genetic mutations
    • Epigenetic alterations
  • Can be locally invasive and spread through the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord
  • Tumor characteristics:
    • Usually well demarcated 
    • Multiple areas of calcification, hemorrhage, and cysts
    • Tumor cells often form ependymal rosettes (perivascular pseudorosettes are the histologic hallmark of ependymomas).
  • Several molecular “profiles” have been identified based on specific combinations of genetic and epigenetic abnormalities within tumor cells:
    • Ependymomas can be classified into the following subgroups according to the profiles:
      • Posterior fossa ependymoma group A (PF-EPN-A)
      • Posterior fossa ependymoma group B (PF-EPN-B)
      • Supratentorial ependymoma with RELA fusion (ST-EPN-RELA)
      • Supratentorial ependymoma with YAP fusion (ST-EPN-YAP)
    • RELA fusion: 
      • Oncogenic fusion between RELA and C11orf95
      • RELA is the principal effector of NF-κB signaling.
    • Subgroup classification is still emerging and requires further study to understand prognostic and therapeutic implications.

Clinical Presentation

The clinical presentation depends on the location of the ependymoma and the age of the patient. Most patients have symptoms for approximately 3–6 months prior to diagnosis.

  • Posterior fossa ependymoma:
    • Signs of increased intracranial pressure Increased Intracranial Pressure Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP) due to obstructive hydrocephalus:
      • Headache (frequently worse in the morning)
      • Nausea and potentially significant vomiting
      • Ataxia
      • Vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo
      • Papilledema
      • Nystagmus
    • Cranial nerve palsies
    • Personality, mood, and cognitive changes
  • Supratentorial ependymomas:
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
    • Focal neurologic deficit
  • Spinal cord ependymoma:
    • Motor and sensory deficits involving descending nerve tracts, ascending nerve tracts, and exiting peripheral nerves
    • Specific deficits depend on the level of the tumor

Diagnosis

Imaging

Imaging is obtained 1st as part of the diagnostic work-up, but histologic evaluation is required for diagnosis. Imaging findings may suggest an ependymoma and guide surgery.

  • MRI:
    • Imaging modality of choice for both the brain and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord
    • Hypointense masses on T1-weighted MRI
    • Hyperintense masses on T2-weighted or proton density MRI
    • Gadolinium enhancement is usually prominent.
  • CT findings:
    • Hyperdense with homogenous enhancement
    • Cysts and calcifications are commonly seen.
  • General findings suggestive of ependymoma (distinguishable from other posterior fossa tumors):
    • Tumor arising from the 4th ventricle
    • Tumor extending down to the craniocervical junction
    • Pronounced extension through the foramina of Luschka
    • Restricted diffusion on diffusion-weighted images
    • Calcifications in the 4th ventricle 
Mri scan reveals an anaplastic ependymoma

Magnetic resonance imaging scan reveals an anaplastic ependymoma extending from the brainstem to the 4th ventricle.

Image: “Giant duodenal ulcers after neurosurgery Neurosurgery Neurosurgery is a specialized field focused on the surgical management of pathologies of the brain, spine, spinal cord, and peripheral nerves. General neurosurgery includes cases of trauma and emergencies. There are a number of specialized neurosurgical practices, including oncologic neurosurgery, spinal neurosurgery, and pediatric neurosurgery. Neurosurgery for brainstem tumors that required reoperation for gastric disconnection: a report of two cases” by BMC Surgery. License: CC BY 4.0

Histologic classification

Ependymoma is based on a histologic diagnosis; therefore, the gold standard for diagnosis is pathologic evaluation of a tissue specimen. Ependymomas are classified by histologic grades according to the WHO.

  • World Health Organization grade I: 
    • Subependymoma: 
      • Rare, benign tumors of the 4th or lateral ventricles in adults
      • Hypocellular tissue consisting of a coarse, glial matrix containing clusters of cells with uniform nuclei and microcysts
    • Myxopapillary ependymoma: 
      • Mostly benign tumors arising in the conus medullaris and filum terminale of the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord
      • Pseudopapillary structures with mucin-rich microcysts
      • Cuboidal cells surrounding a myxoid stroma
  • World Health Organization grade II: classic ependymoma:
    • May arise anywhere in the ventricular system Ventricular System The ventricular system is an extension of the subarachnoid space into the brain consisting of a series of interconnecting spaces and channels. Four chambers are filled with cerebrospinal fluid (CSF): the paired lateral ventricles, the unpaired 3rd ventricle, and the unpaired 4th ventricle. Ventricular System or spinal canal
    • Potential variants include:
      • Papillary variant
      • Clear-cell variant
      • Tanycytic variant
    • Findings include:
      • Solid or papillary mass 
      • Perivascular pseudorosettes: tumor cells appear as a gland surrounding the vasculature (diagnostic of ependymoma)
      • Cells with regular, round-to-oval nuclei and an abundance of granular chromatin
      • Dense fibrillary background
  • World Health Organization grade III: anaplastic ependymoma:
    • Abundant mitotic cells
    • Pseudopalisading necrosis
  • RELA fusion-positive ependymoma: 
    • A new piece of the WHO classification
    • Can include grades II and III
    • Determined based on genetic testing
Who grade iii intracranial ependymoma

World Health Organization grade III intracranial ependymoma:
Perivascular pseudorosettes are seen as well as brisk, mitotic activity, which classifies the tumor as an anaplastic ependymoma.

Image: “Exomic sequencing of four rare central nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System tumor types” by Bettegowda C., et al. License: CC BY 2.5

Other testing

  • CSF cytology:
    • Important in the work-up to evaluate for metastasis
    • Ideally done prior to surgery (debris from surgery can make interpretation difficult)
    • Often contraindicated at presentation due to obstructive hydrocephalus
  • EEG:
    • Not required for diagnosis
    • In patients with supratentorial lesions, diffuse slowing and/or epileptogenic spikes are noted in areas around the tumor.

Management and Prognosis

Management

  • Refer to specialized centers when possible.
  • Intracranial ependymoma:
    • Maximal safe resection
    • Adjuvant radiation therapy
    • Chemotherapy:
      • > 1 year of age: may be used post-radiation for some patients
      • < 1 year of age: used to delay radiation therapy (sparing adverse effects of radiation)
  • Spinal ependymoma:
    • Optimal management includes complete surgical resection. 
    • The role of adjuvant radiation therapy is unclear.
    • No proven role for chemotherapy
  • Corticosteroids: to reduce edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema surrounding the tumor
  • Anticonvulsants: to treat seizures in patients with intracranial ependymoma

Prognosis

  • Survival rates: 
    • Children:
      • 10-year survival: up to 70% in patients with totally resected tumors
      • 10-year survival: 30%–40% in patients with partially resected tumors 
    • Adults:
      • 5-year survival: 67%–85%
      • 10-year survival: 50%–77%
  • Factors affecting survival:
    • Extent of resection (most important factor)
    • Histologic grade and molecular genetic subgroup
    • Location of the tumor
    • Children diagnosed at an older age have a better prognosis.
    • Karnofsky performance status (measures functional status) in adults
  • Long-term survivors of treatment have increased risk of:
    • Neurocognitive deficits
    • Focal neurologic deficits
    • Sensorineural hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
    • Growth and endocrine abnormalities
    • Vasculopathy
    • 2nd malignancy

Differential Diagnosis

  • Medulloblastoma Medulloblastoma Medulloblastomas are malignant primitive neuroectodermal tumors that arise in the posterior fossa in children. Medulloblastomas are the most common malignant brain tumors in children. Patients with medulloblastoma present with symptoms of increased intracranial pressure and cerebellar signs, which both evolve and worsen over weeks to a few months. Medulloblastoma: a tumor arising in the posterior fossa. Medulloblastoma Medulloblastoma Medulloblastomas are malignant primitive neuroectodermal tumors that arise in the posterior fossa in children. Medulloblastomas are the most common malignant brain tumors in children. Patients with medulloblastoma present with symptoms of increased intracranial pressure and cerebellar signs, which both evolve and worsen over weeks to a few months. Medulloblastoma is the most common malignant brain tumor in children. Patients present with symptoms of increased intracranial pressure Increased Intracranial Pressure Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP) and cerebellar signs worsening over time. Treatment is with a combination of surgery, radiation, and chemotherapy. Unlike ependymomas, medulloblastomas rarely have foraminal extension and primary tumors do not occur in the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord.
  • Pilocytic astrocytoma: the 2nd most common brain tumor in children. Magnetic resonance imaging can help distinguish pilocytic astrocytoma from other tumors. A pilocytic astrocytoma is usually cystic with a mural module, or has central necrosis with a thick rim of enhancing tissue. In contrast, ependymomas often arise from the 4th ventricle and are usually accompanied by restricted diffusion on diffusion-weighted images. 
  • Choroid plexus tumors: rare, primary CNS tumors arising from the choroid plexus within the ventricles. Choroid plexus tumors usually present in children with signs and symptoms of hydrocephalus. Histologically, choroid plexus tumors resemble adenocarcinomas and may be associated with Li-Fraumeni syndrome.
  • Oligodendroglioma Oligodendroglioma Oligodendrogliomas are malignant CNS tumors arising from neural glial cell precursors. Oligodendrogliomas often arise in the frontal lobes of the brain and have a generally favorable prognosis when compared to other gliomas. Oligodendrogliomas are the 3rd most common CNS tumor. The most frequent presenting symptom is a seizure. Oligodendroglioma: a CNS tumor arising from oligodendrocytes. Oligodendroglioma Oligodendroglioma Oligodendrogliomas are malignant CNS tumors arising from neural glial cell precursors. Oligodendrogliomas often arise in the frontal lobes of the brain and have a generally favorable prognosis when compared to other gliomas. Oligodendrogliomas are the 3rd most common CNS tumor. The most frequent presenting symptom is a seizure. Oligodendroglioma commonly develops in the cerebral hemisphere (usually the frontal lobe). Presentation may include focal neurological deficits, seizures, and personality changes. Diagnosis is by MRI and biopsy. Management involves surgical resection and may be accompanied by radiation and/or chemotherapy.

References

  1. Capodano, A.M. (2001). Nervous system: Ependymomas. Atlas Genet Cytogenet Oncol Haematol. 5(3), 208–210. 
  2. DeAngelis, L.M., Wen, P.Y. (2018). Primary and metastatic tumors of the nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System. In Jameson, J., et al. (Eds.), Harrison’s Principles of Internal Medicine, 20e. McGraw-Hill. https://accessmedicine-mhmedical-com.aucmed.idm.oclc.org/content.aspx?bookid=2129&sectionid=192016511
  3. Genetic and Rare Disease Information Center. (2021). Ependymoma. Retrieved April 19, 2021, from https://rarediseases.info.nih.gov/diseases/6353/ependymoma
  4. Mayo Clinic. (2019). Embryonal tumors. Retrieved April 19, 2021, from https://www.mayoclinic.org/diseases-conditions/embryonal-tumor/
  5. National Cancer Institute Center for Cancer Research. (2021). Choroid Plexus Tumors Diagnosis and Treatment. Retrieved April 19, 2021, from https://www.cancer.gov/rare-brain-spine-tumor/tumors/choroid-plexus-tumors
  6. National Cancer Institute. (2020). Childhood Ependymoma Treatment (PDQ®)–Patient Version. Retrieved April 19, 2021, from https://www.cancer.gov/types/brain/patient/child-ependymoma-treatment-pdq
  7. National Cancer Institute. (2021). Ependymoma Diagnosis and Treatment. Retrieved April 19, 2021, from https://www.cancer.gov/rare-brain-spine-tumor/tumors/ependymoma
  8. Upadhyaya, S.A., Tinkle, C. (2020). Intracranial ependymoma and other ependymal tumors. UpToDate. Retrieved April 19, 2021, from https://www.uptodate.com/contents/intracranial-ependymoma-and-other-ependymal-tumors
  9. Welch, W.C., Schiff, D., Gerszten, P.C. (2020). Spinal cord tumors. UpToDate. Retrieved April 19, 2021, from https://www.uptodate.com/contents/spinal-cord-tumors

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