Supratentorial ependymoma ZFTA fusion-positive

by Jason Wasserman MD PhD FRCPC
August 6, 2024

This article was written for patients by pathologists. It aims to help patients understand their pathology report for supratentorial ependymoma, ZFTA fusion-positive. It includes sections on its symptoms, causes, genetic changes, diagnosis, WHO grade, and microscopic features.

What is supratentorial ependymoma, ZFTA fusion–positive?

Supratentorial ependymoma, ZFTA fusion-positive, is a type of brain tumour that arises from ependymal cells, which line the ventricles of the brain and the central canal of the spinal cord. This specific type occurs in the supratentorial region, meaning it is located above the tentorium, a membrane that separates the cerebrum from the cerebellum. The term “ZFTA fusion-positive” refers to a genetic alteration involving the ZFTA gene (previously known as C11orf95) that is found in these tumours.

What are the symptoms of supratentorial ependymoma, ZFTA fusion-positive?

The symptoms of supratentorial ependymoma, ZFTA fusion-positive, can vary depending on the tumour’s location and size but may include:

  • Headaches.
  • Nausea and vomiting.
  • Seizures.
  • Weakness or numbness in parts of the body.
  • Vision problems.
  • Balance and coordination difficulties.

What causes supratentorial ependymoma, ZFTA fusion-positive?

The exact cause of supratentorial ependymoma, ZFTA fusion-positive, is not fully understood. It is believed to arise from genetic mutations that occur randomly. The presence of the ZFTA gene fusion is a significant factor in the development of these tumours, leading to uncontrolled growth of ependymal cells.

What genetic changes are found in supratentorial ependymoma, ZFTA fusion-positive?

Supratentorial ependymomas with ZFTA fusion are characterized by a specific genetic alteration involving the ZFTA gene. This fusion results in abnormal activity that promotes tumour growth. Identifying this genetic change is crucial for diagnosing and understanding the tumour’s behaviour.

How is the diagnosis of supratentorial ependymoma, ZFTA fusion-positive, made?

The diagnosis of supratentorial ependymoma, ZFTA fusion-positive, is made through a combination of imaging studies and biopsy. Imaging studies such as MRI (Magnetic Resonance Imaging) can reveal the presence and location of the tumour in the brain. A biopsy, which involves taking a small sample of the tumour tissue, is then performed to confirm the diagnosis. The biopsy sample is examined under a microscope by a pathologist, who looks for specific characteristics and performs genetic testing to identify the ZFTA fusion.

Microscopic features of this tumour

When a pathologist examines a biopsy from a supratentorial ependymoma, ZFTA fusion-positive, they look for specific features under the microscope, including:

  • Tumour cells: Most supratentorial ependymomas with a ZFTA fusion are made up of small cells with round nuclei and fibrillary cytoplasm.
  • Blood vessels: Most tumours contain a network of small branching blood vessels called capillaries.
  • Ependymal rosettes: Rosettes are circular arrangements of tumour cells around an empty space.
  • Perivascular pseudorosettes: Pseudorosettes are tumour cells arranged around blood vessels. This arrangement is rare in this type of tumour but may be seen.

WHO grade

The World Health Organization (WHO) grade system is used to classify the aggressiveness of brain tumours. Tumours are graded on a scale from 1 to 4, with grade 1 being the least aggressive and grade 4 being the most aggressive.

Supratentorial ependymoma, ZFTA fusion-positive, can be classified as either WHO grade 2 or WHO grade 3:

  • WHO grade 2: These tumours have lower cellular density and less aggressive features. They grow more slowly and are less likely to spread.
  • WHO grade 3: These tumours exhibit a higher degree of cellular anaplasia, meaning the cells look more abnormal and less like normal ependymal cells. Anaplasia indicates a more aggressive tumour with a higher potential for growth and spread. Features such as increased mitotic activity (more cell division) and microvascular proliferation (more blood vessels) may also be present.

Molecular tests

Various molecular tests can be performed to identify a ZFTA fusion and confirm the diagnosis. The two most commonly performed tests are next-generation sequencing and fluorescence in situ hybridization (FISH).

Next-generation sequencing (NGS):

  • How it works: NGS is a method for rapid sequencing of large segments of DNA. In this test, DNA from the tumour is extracted and sequenced to identify genetic alterations, including gene fusions.
  • Results: The results are reported as a detailed list of genetic changes found in the tumour, including the presence of the ZFTA fusion if it is detected.

Fluorescence in situ hybridization (FISH):

    • How it works: FISH is a technique that uses fluorescent probes to detect specific DNA sequences in the tumour cells. For ZFTA fusion, probes are designed to bind to the ZFTA gene and its fusion partner, making it possible to visualize the fusion under a fluorescent microscope.
    • Results: The results are reported as positive or negative for the ZFTA fusion based on the presence of fluorescent signals indicating the gene fusion.

Can supratentorial ependymoma, ZFTA fusion-positive recur after surgery?

Yes, supratentorial ependymoma, ZFTA fusion–positive, can recur after surgery. The likelihood of recurrence depends on several factors, including the completeness of the tumour removal during surgery and the tumour’s WHO grade. Tumours that are completely resected and classified as WHO grade 2 have a lower risk of recurrence than those that are partially removed or classified as WHO grade 3. Regular follow-up with imaging studies, such as MRI, is essential to monitor for any signs of recurrence. If the tumour does recur, additional treatments, such as repeat surgery, radiation therapy, or chemotherapy, may be needed to manage the condition.

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