Your pathology report for supratentorial ependymoma

By Jason Wasserman MD PhD FRCPC and Anne F Buckley MD
October 24, 2025

A supratentorial ependymoma is a brain tumour composed of ependymal cells, which normally line the fluid-filled spaces (ventricles) of the brain and the central canal of the spinal cord. “Supratentorial” means the tumour is above the tentorium, the membrane that separates the upper brain (cerebrum) from the lower back part of the brain (cerebellum and brainstem). These tumours can grow within the brain tissue or arise from the lining of the lateral or third ventricles.

What are the symptoms of a supratentorial ependymoma?

The symptoms of supratentorial ependymoma depend on the tumour’s size and exact location. Headache, nausea or vomiting (from pressure build-up), seizures, changes in vision, weakness or numbness on one side of the body, problems with language, and balance or coordination difficulties can occur. Seizures are especially common when the tumour involves the brain’s outer layers (cerebral cortex).

What causes this tumour?

For most patients with a supratentorial ependymoma, the cause is unknown and the tumour is not inherited. Modern testing shows that many supratentorial ependymomas are driven by gene fusions—two genes that are abnormally linked. The most important fusions involve YAP1 or ZFTA (formerly called C11orf95). These fusions help tumour cells grow and are now used to define subtypes because they influence behaviour and treatment planning.

How is the diagnosis made?

Diagnosis combines imaging, microscopic examination, and molecular studies.

  • Imaging (MRI): MRI shows the tumour’s location above the tentorium, its relationship to the ventricles or cortex, and whether it causes swelling or fluid build-up. Contrast enhancement, small cysts (fluid pockets), and areas of bleeding or calcification may be seen.

  • Microscopic examination: A pathologist examines a biopsy or surgical specimen under a microscope.

  • Molecular studies: Genetic and epigenetic tests identify key fusions (YAP1 or ZFTA) and support the final integrated diagnosis, which combines the microscopic and molecular results.

What does it look like under the microscope?

Under the microscope, supratentorial ependymomas are composed of small to medium-sized tumour cells that are fairly uniform in shape. The cells may form ependymal rosettes, which are circular arrangements around a tiny empty space, or perivascular pseudorosettes, where the tumour cells are arranged in a ring around a blood vessel (peri means “around”).

The background tissue often looks fibrillary, meaning it contains fine, hair-like fibres. The pathologist may also describe mitotic activity, which refers to how often cells are dividing, and microvascular proliferation, which means the presence of new small blood vessels within the tumour. Both are signs that the tumour may be growing more quickly.

These microscopic features, along with molecular test results, help determine the CNS WHO grade (see below).

Immunohistochemistry

Immunohistochemistry (IHC) uses antibodies to highlight proteins in the tumour. Ependymomas typically express GFAP (a glial protein) and exhibit a dot-like or ring-like EMA pattern, supporting ependymal differentiation. They are generally negative for OLIG2, helping to distinguish them from many diffuse astrocytomas. Some ZFTA fusion-positive tumours express L1CAM, which can support that diagnosis when used alongside molecular testing. Your report lists each marker as positive or negative and explains what that means.

Molecular tests

Molecular testing confirms the tumour type and identifies the subtype. Some or all of the following molecular tests may be performed and the results will be described in your pathology report.

  • Next-generation sequencing (NGS) or RNA fusion testing: These tests read large sections of DNA or RNA to detect gene fusions. Results list fusions such as YAP1-MAMLD1 (an example of YAP1) or ZFTA-RELA (a common ZFTA partner), and briefly explain their significance.
  • Fluorescence in situ hybridization (FISH): FISH uses fluorescent probes to show whether a gene is broken and fused to another gene. Reports usually state “fusion detected” or “not detected” for YAP1 or ZFTA.
  • DNA methylation profiling: This test surveys chemical tags on DNA and assigns the tumour to a reference class. It can confirm that the tumour is a supratentorial ependymoma and may support YAP1- or ZFTA-fusion biology when routine tests are inconclusive.

Your final diagnosis ties these results together (for example, “Supratentorial ependymoma, ZFTA fusion-positive, CNS WHO grade 3”).

Subtypes of supratentorial ependymoma

YAP1 fusion-positive

This subtype occurs predominantly in young children. It is defined by a YAP1 gene fusion, identified by NGS/RNA fusion testing, FISH, or methylation profiling. Under the microscope, the tumour often looks sharply demarcated with classic ependymal features. With complete surgical removal, many children do well, although all patients require ongoing MRI follow-up. Your report will name the fusion (for example, YAP1-MAMLD1) and explain that it defines this subtype.

ZFTA fusion-positive

This subtype can occur in children and adults and is defined by a ZFTA gene fusion (formerly C11orf95), most commonly ZFTA-RELA, detected by NGS/RNA testing or FISH. Tumours often involve the cerebral cortex, which explains why seizures are a common symptom. Microscopically, they exhibit ependymal patterns and may show increased mitotic activity or microvascular proliferation. Compared with YAP1 fusion-positive tumours, ZFTA fusion-positive ependymomas can behave more aggressively, especially if not completely removed. The report will list the fusion partner and comment on its diagnostic significance.

Unspecified

Sometimes a tumour has microscopic features of a supratentorial ependymoma but no fusion is detected, or testing is not feasible. In that situation, the subtype is reported as unspecified. The integrated diagnosis still confirms “supratentorial ependymoma,” and management is guided by the extent of resection, WHO grade, and clinical/radiologic findings. Further testing may be recommended if tissue becomes available.

WHO grade

Supratentorial ependymomas are assigned a CNS WHO grade (usually grade 2 or grade 3) based on microscopic features such as mitotic activity and microvascular proliferation. Grade provides valuable context, but in modern practice, fusion status (YAP1 vs ZFTA), extent of surgical removal, and imaging are key predictors of behaviour. Your report lists both the grade and the fusion status to guide care.

Prognosis

Outcomes vary by subtype, extent of resection, and grade. In general, YAP1 fusion-positive tumours in very young children can have favourable outcomes after complete removal. ZFTA fusion-positive tumours have a higher risk of recurrence and often require closer follow-up and adjuvant therapy. All patients need scheduled MRI surveillance because late recurrences can occur.

Questions to ask your doctor

  • What does my integrated diagnosis say—YAP1 fusion-positive, ZFTA fusion-positive, or unspecified?

  • What WHO grade is listed, and how does it affect my treatment?

  • Was the tumour completely removed, and will I need radiation therapy?

  • Which molecular tests were performed (NGS/RNA fusion testing, FISH, methylation profiling), and what did they show?

  • How often will I need MRI follow-up, and for how long?

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