Your pathology report for posterior fossa ependymoma

By Jason Wasserman MD PhD FRCPC and Anne F Buckley MD
October 23, 2025

A posterior fossa ependymoma is a type of brain tumour that starts from ependymal cells, which normally line the fluid-filled spaces inside the brain and spinal cord. The posterior fossa is the lower back part of the skull that contains the cerebellum (which controls balance) and the brainstem (which connects the brain to the spinal cord).

These tumours most often arise in and around a space called the fourth ventricle. They are usually well-defined (circumscribed) but can still press on nearby brain structures or block the normal flow of cerebrospinal fluid (CSF), leading to pressure build-up inside the skull.

What are the symptoms of posterior fossa ependymoma?

Symptoms of a posterior fossa ependymoma depend on the tumour’s size and location and on whether it blocks CSF flow.

Possible symptoms include:

  • Headaches (often worse in the morning or when lying down)

  • Nausea and vomiting caused by increased brain pressure

  • Loss of balance, dizziness, or clumsiness

  • Double vision or abnormal eye movements

  • Neck stiffness or head tilt

  • Irritability, tiredness, or an enlarging head in infants and young children

Adults may notice more gradual headaches or balance problems, while babies can present with a rapidly growing head circumference due to fluid build-up (hydrocephalus).

What causes this tumour?

For most people, the cause is unknown and not inherited. Current research shows that the main drivers are epigenetic changes, which are changes in how genes are turned on or off rather than changes to the genes themselves. These affect how the tumour cells grow and behave. Because of this, doctors now classify posterior fossa ependymomas into molecular groups that better predict behaviour and response to treatment than microscopic appearance alone.

How is the diagnosis made?

Diagnosis requires a combination of tests. Imaging tests such as MRI shows the tumour’s location, size, and effect on surrounding structures. Surgery is then performed and tissue is sent to a pathologist for examination under the microscope. Immunohistochemistry and molecular tests then determine the posterior fossa group (A or B) and assess additional changes that influence prognosis. Your final pathology report brings together information from all these steps—imaging, microscopic features, and molecular findings—into what is called an integrated diagnosis.

What does this tumor look like under the microscope?

Under the microscope, posterior fossa ependymomas are made up of small, round cells that sometimes arrange themselves around blood vessels. When tumour cells form a circular pattern around a vessel, it is called a perivascular pseudorosette (perivascular means “around a blood vessel,” and rosette means “ring-shaped”). A true ependymal rosette occurs when cells form a hollow ring around an empty central space.

The pathologist may also comment on mitotic activity, which refers to how often the cells are dividing. A high level of mitotic activity means the cells are dividing quickly. In some tumours, new tiny blood vessels form (microvascular proliferation) to feed the growing mass. These and other features, such as how crowded the cells look, are used to assign a CNS WHO grade, but—importantly—grade alone does not predict how the tumour will behave without molecular information.

Immunohistochemistry

Immunohistochemistry (IHC) is a test that uses antibodies to highlight certain proteins inside the tumour cells. These patterns confirm the tumour type and help determine its molecular group.

Ependymomas typically produce proteins such as GFAP (a marker of glial origin) and EMA, which often shows a dot-like or ring-shaped pattern.

A particularly important IHC test for this tumour is H3 K27me3 (also written H3 p.K28me3). This test looks for a specific chemical tag on a histone protein inside the cell nucleus.

  • If the tumour cells lose this staining, the diagnosis supports posterior fossa group A (PFA).

  • If the tumour cells retain this staining, it is more likely posterior fossa group B (PFB).

Normal brain and blood vessel cells in the sample retain staining and act as an internal control, showing that the test worked.

Molecular tests

Molecular tests provide deeper information about the tumour’s DNA and are essential for accurate classification. Your report will usually list which tests were performed, the results, and what those results mean.

DNA methylation profiling

This test reads thousands of chemical marks on DNA to identify a characteristic “methylation pattern.” Each tumour type has a unique pattern, allowing classification as PFA, PFB, or occasionally another ependymoma type. This method is considered the gold standard for confirming the molecular group.

Copy-number analysis

This test looks for missing or extra pieces of chromosomes. These are called copy-number changes. For posterior fossa ependymomas, gain of chromosome 1q is a common finding and is associated with a higher risk of recurrence. Your report may mention this or other chromosome changes such as 22q loss.

Histone and EZHIP testing

Many PFA ependymomas have changes that affect how histone H3 proteins are modified. Most show over-expression of EZHIP, a protein that mimics a mutation known as H3 K27M. Both result in loss of normal histone methylation (the H3 K27me3 mark). These findings confirm PFA biology. Rarely, actual H3 K27M mutations or small EZHIP gene mutations are detected.

Each of these results helps confirm the correct group and provides information on how the tumour might behave over time.

Groups: PFA, PFB, and NOS/NEC

Posterior fossa ependymomas are separated into groups because the biology, typical patient age, and expected behaviour differ. Knowing the group helps doctors predict prognosis and tailor treatment.

Posterior fossa group A (PFA)

PFA tumours occur mostly in infants and young children. They usually show loss of the H3 K27me3 marker and classify as PFA by DNA methylation. These tumours are more likely to return (recur) after treatment, especially when complete removal is not possible or when there is a 1q gain.

Posterior fossa group B (PFB)

PFB tumours are more common in adolescents and adults. They retain H3 K27me3 staining and classify as PFB by methylation. They tend to behave less aggressively than PFA tumours, and long-term control is often achievable when treated appropriately.

Not otherwise specified (NOS) / not elsewhere classified (NEC)

Sometimes, the tumour shows the microscopic appearance of posterior fossa ependymoma, but the laboratory tests cannot confirm its molecular group.

  • NOS means molecular testing could not be performed, for example because there was too little tissue.

  • NEC means molecular testing was done but the tumour’s pattern did not fit any recognized group.

In these situations, the diagnosis will still read posterior fossa ependymoma, but it will include “NOS” or “NEC” after the name to indicate molecular uncertainty. Doctors then rely more on imaging findings, surgical results, and any available chromosomal information, such as 1q status, to guide care.

WHO grade

All posterior fossa ependymomas are given a CNS WHO grade, usually grade 2 or grade 3. The grade is based on microscopic features such as how many cells are dividing (mitotic activity) and whether new small blood vessels (microvascular proliferation) have formed.

Your report will list this grade because it remains part of the official WHO classification. However, research shows that WHO grade alone does not reliably predict behaviour in posterior fossa ependymomas. Instead, the molecular group (PFA vs PFB), the extent of tumour removal, and chromosome 1q status are much stronger predictors of outcome. Modern pathology reports therefore combine these elements into an integrated diagnosis that provides a more accurate picture of risk.

Prognosis

Outcomes depend on age, molecular group, extent of surgical removal, and genetic findings. In general, PFA tumours in younger children have a higher risk of recurrence than PFB tumours in older patients. Across all groups, a gross total resection improves outcome, and 1q gain is an adverse marker. Your neuro-oncology team will interpret your integrated report to develop a personalized follow-up plan, which typically includes regular MRI scans.

Questions to ask your doctor

  • Does my report say PFA, PFB, or NOS/NEC, and how was this determined?

  • What does the H3 K27me3 test show?

  • Was DNA methylation profiling or chromosome 1q testing performed?

  • What WHO grade is listed, and how does it relate to the molecular findings?

  • Was the tumour completely removed, and how does that affect treatment?

  • What therapy is recommended, and what is my follow-up schedule?

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