Supratentorial Ependymoma

Supratentorial ependymoma is a rare variant of ependymoma often found in adults, characterised by intracranial masses with a rosette pattern microscopically and a cystic appearance with an enhancing mural nodule on neuroimaging.

Description

Supratentorial ependymomas are rare neoplasms that originate from the ependymal cells lining the ventricles within the supratentorial region of the brain. They are a subset of ependymomas, a family of gliomas, but they differ in their molecular characteristics, age of presentation, and prognosis from their infratentorial counterparts.

Pathogenesis

The pathogenesis of supratentorial ependymomas is not completely understood. Similar to other ependymomas, they are believed to originate from radial glial cells, the precursors to ependymal cells. Supratentorial ependymomas often have genetic alterations that differ from those seen in infratentorial ependymomas. Most notably, they frequently have alterations in the RELA gene, resulting in the RELA fusion-positive subtype of ependymomas.

Subtype

• RELA Fusion-positive Ependymoma: The most common subtype (seen in 70%) of supratentorial ependymomas, characterised by a genetic fusion involving the RELA gene, leading to constitutive activation of the NF-kB pathway. Associated with a worse prognosis compared to other subtypes.
• YAP1 Fusion-positive Supratentorial Ependymoma: Another subtype found in the supratentorial compartment, characterised by fusions involving the YAP1 gene.
• ST-EPN-RELA Negative: These are supratentorial ependymomas that do not express the RELA fusion. They tend to have a more diverse genetic and phenotypic landscape compared to RELA fusion-positive cases.

Epidemiology, Risk Factors & Associations

• Supratentorial ependymomas make up only a small proportion of all ependymomas (most are seen in the infratentorial compartment).
• They more commonly occur in children but can be seen in adults.
• There are no known environmental or lifestyle-related risk factors for supratentorial ependymomas.
• Associated with Multiple Intracranial Schwannomas, Meningiomas, and Ependymomas (MISME) syndrome, a variant of Neurofibromatosis Type 2 (NF2) (5-10% of cases).

Clinical Features

• Clinical manifestations are primarily related to mass effects and may include headache, nausea, vomiting, and seizures.
• Neurological deficits can occur, such as changes in vision or motor weakness, depending on the location of the tumour.

Complications

• Complications can include obstructive hydrocephalus, haemorrhage within the tumour, and local or CSF spread of disease.

Pathological Features

Histopathology

• Macroscopic: Typically, these tumours are well-defined and can have cystic components.
• Microscopic: Characteristic features include perivascular pseudorosettes or ependymal rosettes.

Genetics

• RELA fusion: Constitutive activation of the NF-kB pathway, most commonly seen in supratentorial ependymomas in children. Often associated with worse prognosis.
• YAP1 fusion: Characteristic of a subtype of supratentorial ependymoma, typically associated with a more favourable prognosis than RELA fusion-positive tumours.
• RELA fusion-negative: These tumours show a more diverse genetic landscape, including various other gene mutations and chromosomal abnormalities. Their clinical behaviour and prognosis can vary widely.

Serological

There are no specific serological markers for supratentorial ependymoma.

Biochemistry

There are no specific biochemical markers for supratentorial ependymoma.

Radiological Features

General Features

• Typically demonstrates a well-defined, contrast-enhancing mixed solid-cystic hemispheric mass in the supratentorial brain.
• Frontal lobe is the most common location of cortically-based tumours. Suprasellar origin is rare.
• Calcification is relatively rare compared to infratentorial ependymomas.
• MISME: In patient with this variant of NF2, may see bilateral vestibular schwannomas, multiple meningiomas, and, less commonly, spinal ependymomas.

CT

• Non-contrast: Cystic component with iso- to hypodense to brain parenchyma solid component, with possible calcifications.
• Contrast-enhanced: Prominent heterogeneous enhancement.

MRI

• T1WI: Iso- to hypointense to brain parenchyma.
• T2WI/FLAIR: Hyperintense. Surrounding vasogenic oedema is typical.
• T1 C+: Heterogeneous enhancement, with possible cystic areas or necrosis.
• DWI/ADC: Variable, typically no restricted diffusion.
• SWI/GRE: May show foci of signal loss suggestive of haemorrhage or calcification.

NM

• PET FDG: Variable uptake, typically low to moderate.

Grading and Staging

Grading is performed according to the WHO classification system:

• Grade II: Supratentorial Ependymoma
• Grade III: Supratentorial Anaplastic Ependymoma

Diagnosis

Diagnosis requires a combination of imaging findings and histopathological confirmation. Molecular testing for RELA fusion can help confirm the diagnosis.

Differential Diagnosis

• Glioblastoma: More common in adults, characteristically a hetoerogenous highly cellular supratentorial mass with central necrosis and a surrounding rim of enhancement. Tends to have a more aggressive course.
• Low-grade Anaplastic Astrocytoma: Less common, but also presents with a cellular, heterogeneous mass. No central necrosis seen.
• Embryonal Tumour With Multilayered Rosettes (ETMR): Typically seen in children under the age of 5. Characteristically demonstrates minimal surrounding oedema.
• Atypical Teratoid/Rhabdoid Tumour (AT/RT): Common in very young children. High cellularity evident with increased diffusion-weighted imaging (DWI) signal and decreased apparent diffusion coefficient (ADC).
• Ganglioglioma: Most common in the temporal lobe, may appear complex. Consider desmoplastic infantile ganglioglioma (DIG) in infants or young children.
• Other Astrocytomas (e.g., Anaplastic Astrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma): Can present as complex, heterogeneous-appearing masses.
• Oligodendroglioma: Less common in children, typically located in the cerebral hemispheres, including cortical and subcortical locations. Characteristically demonstrates calcifications and scalloping of the inner table of the skull.
• Pleomorphic Xanthoastrocytoma (PXA): Typically presents as a cortically based, enhancing mass with a dural tail, most commonly in the temporal lobe. May be cystic with solid, enhancing components.
• Metastasis: Should be considered in adults with multiple lesions or a known primary malignancy.

Management

Treatment is primarily surgical, aiming for gross total resection. This is followed by adjuvant radiotherapy. The role of chemotherapy is not well established and is typically reserved for recurrent or residual disease. Long-term follow-up with neuroimaging is recommended given the risk of recurrence.