Supratentorial Ependymoma: Understanding Your Pathology Report

By Jason Wasserman MD PhD FRCPC and Anne F Buckley MD
September 10, 2026

A supratentorial ependymoma is a brain tumor made of ependymal cells, which normally line the brain’s fluid-filled spaces and the central canal of the spinal cord. Supratentorial means the tumor sits above the tentorium, the membrane separating the upper brain from the cerebellum and brainstem below. These tumors can grow within the brain tissue itself or arise from the lining of the lateral or third ventricles.

A supratentorial ependymoma is defined not by how it looks under the microscope, but by which fusion gene it carries. This article explains what appears on the pathology report and what the ZFTA and YAP1 results mean. It also explains why older sources describe the outlook for these tumors more pessimistically than current evidence supports. For an overview of the whole family, see our article on ependymoma.

What are the symptoms of a supratentorial ependymoma?

The symptoms of a supratentorial ependymoma depend on the tumor’s size and its exact location within the upper brain.

Seizures. Especially common when the tumor involves the cerebral cortex, the brain’s outer layer. This is often the symptom that leads to the scan.
Headache, nausea, and vomiting. This can happen when pressure builds up inside the skull.
Weakness or numbness on one side of the body.
Vision changes.
Problems with language. When the tumor affects the areas controlling speech and understanding.
Balance or coordination difficulties.

What causes a supratentorial ependymoma?

For most patients with a supratentorial ependymoma, the cause is unknown, and the tumor is not inherited. It is not linked to diet, activity, injury, or anything in the environment.

Modern testing shows that most of these tumors are driven by a fusion gene, formed when two separate genes join abnormally. The fusions that matter involve either ZFTA (formerly called C11orf95) or YAP1. These fusions drive tumor cell growth. Because they behave differently, they are now used to define the subtype rather than noted as an extra finding.

How is the diagnosis made?

Diagnosing a supratentorial ependymoma combines imaging, microscopic examination, and molecular studies. The modern report brings these together into an integrated diagnosis.

MRI shows the tumor’s location above the tentorium and its relationship to the ventricles or the cortex. Small fluid pockets, areas of bleeding, or calcium deposits may be visible. A pathologist then examines a biopsy or, more often, the tumor removed at surgery. Molecular tests identify the fusion and complete the diagnosis.

Because ependymomas can spread through the cerebrospinal fluid, doctors often order an MRI of the whole spine and sometimes collect a fluid sample as part of the initial assessment. This is standard practice, not a sign that spread is expected.

What does a supratentorial ependymoma look like under the microscope?

Under the microscope, a supratentorial ependymoma is made of small to medium-sized cells that are fairly uniform in shape. The cells may form ependymal rosettes, which are rings around a tiny space. They may also form perivascular pseudorosettes, rings around a blood vessel with a clear zone of fine fibers in between.

The background tissue often looks fibrillary, meaning it contains fine hair-like fibers. The pathologist also describes mitotic activity, which is how often cells divide, and microvascular proliferation, which means new small blood vessels within the tumor. Some tumors show necrosis, meaning dead tumor tissue. These features determine the CNS WHO grade.

Immunohistochemistry

Immunohistochemistry uses antibodies to highlight proteins in a supratentorial ependymoma, and the pattern confirms the tumor type. Your report lists each marker as positive or negative.

GFAP. A glial protein, positive in ependymomas, confirming the tumor’s glial origin.
EMA. Shows a distinctive dot-like or ring-like pattern inside the cells, which is close to a signature for ependymoma.
OLIG2. Usually negative, which helps separate ependymoma from many diffuse astrocytomas.
L1CAM. Often positive when a ZFTA fusion is present, and negative in YAP1 fusion tumors. It is a useful pointer but not a substitute for molecular testing.

Molecular tests

Molecular testing confirms that a tumor is a supratentorial ependymoma and identifies its subtype. Some or all of the following may be performed, and the results will be described in your report.

RNA fusion testing or next-generation sequencing. Reads large sections of DNA or RNA to detect gene fusions. The report names the fusion found, for example ZFTA-RELA or YAP1-MAMLD1.
Fluorescence in situ hybridization. Uses fluorescent probes to show whether a gene is broken and joined to another. Reports usually state whether a fusion was detected or not for ZFTA or YAP1.
DNA methylation profiling. Surveys chemical tags on DNA and matches the pattern against a reference library. It can confirm the tumor type when routine tests are inconclusive.
Copy-number analysis. Looks for missing or extra pieces of chromosomes, including loss of the CDKN2A and CDKN2B genes, described below.

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

ZFTA fusion-positive

This is the most common subtype of supratentorial ependymoma, accounting for roughly 70 to 80 percent. It occurs in both children and adults. The tumor is defined by a fusion involving the ZFTA gene, most often joined to a partner gene called RELA. Clinicians detect it with RNA fusion testing, sequencing, or FISH. These tumors often involve the cerebral cortex, which explains why seizures are such a common first symptom.

The outlook for this subtype has been revised, and this matters if you have read about it elsewhere. Earlier retrospective studies reported poor outcomes for ZFTA fusion-positive tumors, with 10-year survival as low as 49 percent. More recent work has not confirmed that. A pooled international study of 108 children treated with modern approaches reported 5-year survival of 87 percent and 10-year survival of 73 percent. Roughly 63 percent were free of progression at 10 years. An analysis from a large clinical trial found that children with these tumors did significantly better than those with posterior fossa group A tumors.

The difference appears to reflect current treatment practices. In the pooled study, roughly 8 in 10 had the whole tumor removed and roughly 9 in 10 received radiation afterward. If a source you found describes this subtype as having a poor outlook, it is likely drawing on older literature.

CDKN2A and CDKN2B. Some ZFTA fusion-positive tumors have lost both copies of these two neighboring genes, a finding reported in roughly 16 to 17 percent. Several studies have linked this loss to shorter survival, but an analysis from a large clinical trial found no significant difference. It is best understood as a candidate marker still being validated rather than a settled prognostic factor. Two stains, p16 and MTAP, can suggest the loss when molecular testing is not available.

YAP1 fusion-positive

This subtype of supratentorial ependymoma is much less common, making up well under 1 in 10 cases, and it occurs predominantly in infants and very young children. It is defined by a fusion involving the YAP1 gene, most often joined to a partner called MAMLD1.

Under the microscope, these tumors often look sharply demarcated, with classic ependymal features. They are typically negative for L1CAM, one way they are distinguished from the ZFTA subtype. Their biology is genuinely different, and outcomes after complete surgical removal are usually excellent. Because the number of patients studied is small, follow-up is still thorough and long-term.

When no fusion is found

Sometimes a tumor has all the microscopic features of a supratentorial ependymoma but no fusion is detected, or testing cannot be performed. The subtype is then reported as unspecified, and the integrated diagnosis still confirms supratentorial ependymoma. Management depends on the extent of removal, the WHO grade, and the imaging findings. Further testing may be recommended if more tissue becomes available.

Two other situations are worth knowing about. A ZFTA fusion is occasionally found in a posterior fossa tumor rather than above the tentorium, in roughly 1 in 16 of these tumors. That changes how it is followed. ZFTA can also partner with genes other than RELA, and some of those tumors are not ependymomas at all. This is one reason the diagnosis rests on the whole picture rather than the fusion alone.

What does the WHO grade mean?

Supratentorial ependymomas are assigned a CNS WHO grade, usually grade 2 or grade 3. The system used is the World Health Organization classification of central nervous system tumors, 5th edition, published in 2021. The grade reflects microscopic features such as mitotic activity and microvascular proliferation.

The grade appears on the report because it is part of the official classification. In current practice, fusion status, extent of removal, and imaging findings are stronger predictors of tumor behavior. This is why the report presents the grade alongside the molecular findings rather than on its own.

How much of the tumor was removed

How completely a supratentorial ependymoma was removed is the strongest factor that treatment can influence, and it is weighed alongside the fusion result.

Brain tumors are not reported with inked surgical margins in the way tumors elsewhere in the body are. The neurosurgeon describes what was achieved during the operation, and an MRI within a day or two confirms it. Gross total resection means no visible tumor remains. Subtotal or partial resection means some remains.

Complete removal is more common here than in the posterior fossa because these tumors are farther from the brainstem and the nerves emerging from it. Where tumor does remain, a second operation is sometimes considered.

What is the prognosis?

The outlook for a supratentorial ependymoma depends on the subtype, how completely the tumor was removed, and whether radiation was given.

YAP1 fusion-positive. The more favorable subtype. Outcomes after complete removal are usually excellent, though sample sizes are small.
ZFTA fusion-positive. In modern series, roughly 87 percent of children were alive at five years and roughly 73 percent at ten years. Older literature reports substantially worse figures.
Extent of removal. Complete removal followed by focal radiation gives the best reported outcomes, and this holds across the subtypes.
Unspecified. Outlook is based on the extent of removal, grade, and imaging rather than molecular results.

One feature applies across all subtypes. Supratentorial ependymomas can return years after treatment, so MRI follow-up continues long after treatment ends. That is how this tumor is properly monitored, not as a sign that something has gone wrong.

These figures come from groups of patients treated over many years and cannot predict what will happen to one person. Your neuro-oncology team can provide numbers that match your subtype and the extent of removal.

What happens after the diagnosis?

A team of a neurosurgeon, neuro-oncologist, radiation oncologist, and neuropathologist plans care for a supratentorial ependymoma. Because the fusion result is central to the diagnosis, the complete report can take longer than expected, and some decisions wait for it.

Surgery is the mainstay of treatment, and removing as much tumor as can safely be taken is the goal. Most patients then receive focal radiation to the tumor bed, and higher doses have been associated with better outcomes. Chemotherapy has a limited role here. In the largest modern series, it did not appear to add a survival benefit, and it is used mainly in infants to delay radiation until the brain is more developed.

Follow-up MRI covers the whole brain and spine and continues for many years. Long-term follow-up also monitors treatment effects on learning, hormone function, and, where seizures were the first symptom, whether seizure medication can eventually be reduced.

Questions to ask your doctor

Does my integrated diagnosis say ZFTA fusion-positive, YAP1 fusion-positive, or unspecified?
Which molecular tests were used to determine that, and are any still pending?
If no fusion was found, can further testing be done?
Was CDKN2A and CDKN2B loss looked for, and what did that show?
What CNS WHO grade is listed, and how much weight does it carry in my case?
Was the whole tumor removed, and was an MRI done afterward to confirm?
If tumor remains, is a second operation being considered?
Was the rest of my spine imaged, and was the cerebrospinal fluid examined?
Is radiation recommended, and at what dose?
Would chemotherapy be used in my case, and if so, for what?
I have read that this subtype has a poor outlook. Does that reflect current evidence?
How often will I need follow-up MRI, and for how many years?
If seizures were my first symptom, how long will I need seizure medication?
Has a pathologist who specializes in nervous system tumors reviewed the slides?