Pilocytic Astrocytoma

What is Pilocytic Astrocytoma?

Pilocytic astrocytoma, also known as cystic cerebellar astrocytoma or juvenile pilocytic astrocytoma, is a type of tumor found in the brain. It was first identified in 1931 by Harvey Cushing. Pilocytic astrocytomas are typically slow-growing, well-defined, and considered low-grade or non-cancerous. These tumors are most commonly found in children and young adults. They originate from astrocytes, which are star-shaped cells that support nerve cells in the brain.

According to the World Health Organization (WHO) system for classifying central nervous system (CNS) tumors, pilocytic astrocytomas are classified as grade I gliomas. This means they are typically slow growing and less likely to spread, so they usually have a good prognosis for the patient.

Although pilocytic astrocytomas are most often found in the cerebellum (a region at the back of the brain), they can also appear along the optic pathways, hypothalamus, and brainstem. In some cases, especially in young adults, these tumors can occur in the cerebral hemispheres or the main parts of the brain. Depending upon where the tumor is located, the symptoms and treatments can vary. This rewritten explanation mainly concentrates on pilocytic astrocytomas that are found in the cerebellum.

Recently, in 2021, the WHO updated their system for classifying CNS tumors and grouped pilocytic astrocytomas with other similar types of tumors, such as pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, and choroid gliomas.

What Causes Pilocytic Astrocytoma?

Neurofibromatosis type 1 (NF1), a genetic disorder, is often linked with a type of brain tumor known as pilocytic astrocytomas. In fact, up to 20% of people with NF1 end up developing this type of tumor, usually in the optic pathway, which includes parts of the brain involved in vision. However, it’s important to note that most pilocytic astrocytomas are thought to be caused by random mutations, rather than being inherited.

Studies have found that changes in the BRAF gene and alterations in a process called mitogen-activated protein kinase (MAPK) signaling, which van be involved in controlling cell growth, are common in these tumors. About 60% of pilocytic astrocytomas found in the cerebellum, a part of the brain that plays an important role in motor control, have a specific gene fusion involving the BRAF gene. The BRAF gene is a type of proto-oncogene, which are normal genes that can become cancer-causing genes when they mutate.

Other common mutations in pilocytic astrocytomas include a specific point mutation in the BRAF gene, referred to as BRAFV600E. This mutation pops up in 5% to 10% of all cases, but it’s more common in tumors located above the tentorium, a membrane in the brain that separates the cerebellum from the cerebral hemispheres.

Risk Factors and Frequency for Pilocytic Astrocytoma

Brain tumors are the most common type of solid cancer in children. Among these, the most frequent is a type called pilocytic astrocytoma. This tumor is often diagnosed in young individuals, with most cases occurring before the age of 20. Even though pilocytic astrocytoma can also develop in adults, it is usually found in younger adults.

• Pilocytic astrocytoma is the most common brain tumor in children.
• The rate of pilocytic astrocytoma is 0.8 per 100,000 individuals.
• 75% of these cases occur before the age of 20.
• It makes up 15% of all brain tumors in children.
• This condition accounts for 27% to 40% of all pediatric tumors in the rear part of the skull.
• While pilocytic astrocytoma occurs in adults as well, it’s primarily found in younger adults.
• In adults, it amounts to 5% of all primary brain tumors, often located in the cerebellum, the part of the brain responsible for balance and coordinating movements.
• However, they are frequently found in the temporal and parietal lobes, the areas of the brain involved in processing sensory information and governing movement and coordination, respectively.

Signs and Symptoms of Pilocytic Astrocytoma

Pilocytic astrocytoma is a type of brain tumor. The symptoms often depend on the tumor’s location and how it’s growing. These symptoms usually start to show up gradually. If the tumor is in the back of the brain, known as the posterior fossa, patients may experience symptoms due to pressure from the tumor. Such symptoms can include:

• Headache
• Nausea
• Vomiting
• Swelling of the optic disc, or papilledema

Seizures are uncommon if the tumor is located here. In infants under 18 months, if the tumor causes a buildup of fluid in the brain, or hydrocephalus, before the bones of the skull are fully fused, the child’s head may get larger and the skull sutures may spread apart.

Back-of-the-brain tumors can also lead to problems with the cranial nerves, which control various functions such as eye movement, facial sensation, and chewing. Patients might experience double vision due to an abducens nerve palsy (a condition that affects the nerve controlling eye movement). They may also have blurred vision as a result of swollen optic discs. If the tumor is located in the cerebellar hemisphere, which is a part of the brain that helps with balance and coordination, patients could have symptoms like:

• Difficulty with coordinated movements, or peripheral ataxia
• Problems with judging distance, or dysmetria
• Tremors when intending to move, also known as intention tremor
• Involuntary eye movement, or nystagmus
• Trouble with articulation, or dysarthria

If the tumor is in the vermis, which is another part of the cerebellum, patients might have a wide-based walk, difficulty with balance, and shaky, unsteady movements. Tumors affecting the hypothalamus, a gland that regulates several hormones, can result in hormonal imbalances or trouble with growth. A physical exam of the patient often shows signs of increased pressure in the brain and problems with cerebellar function. Specific neurological signs will depend on exactly where the tumor is and how it’s affecting nearby structures.

Testing for Pilocytic Astrocytoma

If your doctor suspects you have a tumour known as pilocytic astrocytoma, they will likely want to do some imaging tests to confirm this. The most common test used is a type of scan called a magnetic resonance imaging (MRI) scan, which can be done with and without a dye (contrast). This type of scan uses a magnetic field and radio waves to create detailed images of your brain. The MRI is particularly useful for these kinds of situations as it doesn’t use radiation, which can be harmful, especially for those with a genetic disorder known as Neurofibromatosis Type 1 (NF1).

However, if your symptoms are severe and your condition is believed to be unstable, an immediate computed tomography (CT) scan might be needed. A CT scan combines a series of X-ray images taken from different angles to create cross-sectional images of your brain.

In children, sometimes the entire brain and spinal cord (known as whole neuroaxis) are scanned, especially when dealing with certain types of tumours that can spread. While pilocytic astrocytomas don’t typically spread in this way, a more aggressive variant called pilomyxoid astrocytoma can. In situations where this is suspected, your doctor may recommend whole neuroaxis imaging.

Pilocytic astrocytomas can show up differently on scans. They often have a large cystic component, which looks like a fluid-filled sac, with an enhancing nodule. Sometimes, the wall of the cyst also enhances, meaning it shows up more brightly on the scan. Some tumors are solid with little or no cystic component, and some may show calcium deposits. Most are located near the brain’s ventricles (fluid-filled spaces).

The content of the cyst in a pilocytic astrocytoma is protein-rich and often looks denser than cerebrospinal fluid (CSF), the fluid that surrounds your brain and spinal cord, on a scan. When using an MRI scan, the cyst content typically shows up as a bright signal on T2-weighted images, similar to CSF. The enhancing nodule often appears bright on T2-weighted images and dull or equal brightness on T1-weighted images. The way the nodule enhances can help your doctor distinguish it from other types of gliomas, a group of brain and spinal cord tumours.

Treatment Options for Pilocytic Astrocytoma

The primary treatment for the illness usually involves a surgical procedure to remove the diseased tissue extensively. However, if the disease spread involves sensitive areas like the brainstem or cranial nerves, removing all diseased tissue might not be possible. Generally, the diseased nodule is removed rather than the cyst wall (the outer layer of the cyst). But, if the cyst wall is thick, it may be considered as part of the nodule and thus it gets removed.

Patients typically don’t need traditional chemoradiation treatment immediately; consistent check-ups and image testing are more preferable in the initial stages. Radiation therapy in the brain region can have significant harmful effects. If the disease reoccurs, surgical removal is again considered, if doable. Radiation therapy becomes suitable if it is impossible to perform surgery or if the presence of cancerous cells is found.

Advanced radiation therapy (known as stereotactic radiosurgery) has indicated excellent results for remaining and recurring tumors in some studies. Despite their success, there’s criticism about the length of time patients are tracked and concerns that stereotactic radiosurgery might accelerate malignant cell development. Notably, patients with Neurofibromatosis type 1 (NF1), a genetic disorder predisposing them to further tumor development, should typically avoid radiation unless necessary.

Chemotherapy, a type of cancer treatment that uses drugs to kill cancer cells, is not typically used as an initial treatment for pilocytic astrocytoma. However, several trials have shown a survival rate between 34% and 45% over five years without cancer progression. As these tumors tend to have mutations affecting the MAPK signaling pathway (a chain of proteins in the cell that sends signals from a receptor on the surface of the cell to the DNA in the center of the cell), certain inhibitors have been studied with varying success rates.

Multiple strategies are available to manage excess cerebrospinal fluid (CSF) build-up in the brain (hydrocephalus) in patients who are neurologically stable. These include:

• Draining the CSF at the time of surgery, followed by immediate tumor removal.
• Surgical removal without CSF drainage. If the hydrocephalus persists after the surgery, then CSF drainage is performed.
• Draining CSF before image studies if patients require anesthesia.

If the patient is not stable neurologically due to hydrocephalus or pressure on the brainstem, urgent treatment is necessary. For patients presenting with hydrocephalus, some specialists recommend initial CSF drainage before definitive surgery, using approaches such as an external ventricular drain (a system of emptying cerebrospinal fluid), endoscopic third ventriculostomy (a procedure to allow cerebrospinal fluid to bypass obstructions and flow through the normal pathways), or ventricular-peritoneal shunt (a device to redirect the cerebrospinal fluid from a ventricle in the brain to the abdominal cavity). In some medical centres, these methods may be performed concurrently with surgery, followed by immediate tumor removal. Factors to consider with CSF drainage include the risk of upward displacement of the brain and CSF infection from the ventricular-peritoneal shunt or external ventricular drain.

What else can Pilocytic Astrocytoma be?

Diagnosing pilocytic astrocytomas – a type of brain tumor – involves distinguishing them from other similar brain tumors and lesions. This involves looking at images of the brain, considering the patient’s demographic details, and studying the microscopic structure of brain tissue. The goal is to differentiate pilocytic astrocytomas from other low-grade and high-grade gliomas (other types of brain tumors), and conditions that are not caused by tumor growth.

The most common types of tumors in the back of the brain in children are:

• Medulloblastoma: These are usually found in the middle of the brain, at the roof of the fourth ventricle, or in the vermis of the brain. Less than 10% of these tumors show calcification, which is when calcium builds up in the body’s tissues.
• Diffuse pontine glioma: These often lead to complications with multiple cranial nerves.
• Ependymoma: These usually spring up from the floor of the fourth ventricle and calcification is common.

Other types of lesions in the back of the brain in children include:

• Hemangioblastoma
• Atypical teratoid or rhabdoid tumor
• Cerebellar abscess
• Choroid plexus papilloma
• Metastasis from cancers such as neuroblastoma, rhabdomyosarcoma, or Wilms tumor

For adults, the types of lesions in the back of the brain include:

• Metastasis, which is the most common type
• Hemangioblastoma, making up 7% to 12% of all lesions in the back of the brain in adults. It’s often a vascular tumor that comes with a cyst.
• Brainstem glioma
• Abscesses
• Cavernous malformation
• Ischemic stroke
• Cerebellar hemorrhage

What to expect with Pilocytic Astrocytoma

A pilocytic astrocytoma is a type of slow-growing brain tumor which can often be cured if the entire tumor is surgically removed. As with many tumors, how much of the tumor can be removed is often the best indicator of patient recovery. If the entire tumor is successfully removed, the survival rate after 10 years can be as high as 95%, and it is rare for the tumor to come back.

If the tumor does return, this typically occurs within a couple of years. According to a rule known as Collins’ law, one way medical professionals estimate the risk period for tumor recurrence is adding nine months to the child’s age at the time of diagnosis. Going by this rule, if the pilocytic astrocytoma doesn’t come back within this time, it might be considered cured. However, patients should continue to be monitored for late recurrence. Some experts even recommend upto three years of follow-up medical imaging to check for tumor recurrence in childhood pilocytic astrocytoma, due to its low risk of coming back.

That being said, if the entire tumor is not able to be removed, there is a chance that it could come back and symptoms may worsen. Certain risk factors have been linked to tumor recurrence as well, such as if the tumor is solid, grows outside of its usual location, or spreads into the brain tissue.

Patients aged 1 or younger generally have the worst recovery prospects, which might be due to a more common variant in this age group called pilomyxoid astrocytoma. In adults, the 5-year survival rate for pilocytic astrocytoma is approximately 85%. However, 70% remain disease-free and the recurrence rate is about 20%.

Possible Complications When Diagnosed with Pilocytic Astrocytoma

Patients who have a specific type of brain tumor called a pilocytic astrocytoma can face complications, especially if it isn’t treated quickly and properly. For instance, they may have hydrocephalus, which is when there’s an unusual buildup of fluid in the cavities deep within the brain. This happens because the pathways where fluid usually circulates are blocked. As a result, pressure can build up inside the skull, leading to a host of other problems.

If the tumor is found in a part of the brain called the posterior fossa, patients might end up needing a special surgical device called a VP shunt to drain the excess fluid. This may result in them becoming dependent on this shunt for life.

Complications:

• Increased pressure inside the brain or skull (Hydrocephalus)
• Possibility of relying on a VP shunt, draining excess brain fluid, for life

Tumor growth can affect vital parts of the brain and lead to issues with movement, sensation, or cognition. Complications after surgery may include infection, bleeding, or damage to the surrounding brain tissue, which may make neurological issues even worse. There’s also a risk that the tumor may return, requiring continual monitoring and possibly more treatment.

Patients may suffer long-term effects from the radiation or chemotherapy used in treatment, affecting their quality of life. Although rare, some pilocytic astrocytomas can change and become cancerous. Most of these changes seem to occur after the patient has received radiation therapy.

Further complications:

• Motor, sensory, or cognitive impairments due to tumor growth
• Possible infection, bleeding, or surrounding brain tissue damage post-surgery
• Risk of tumor recurrence
• Quality of life changes due to long-term effects of radiation or chemo treatment
• Rarity of pilocytic astrocytomas degenerating to malignant form, mainly after radiation therapy

Preventing Pilocytic Astrocytoma

No specific lifestyle factors have been found to increase or decrease the risk of developing pilocytic astrocytoma, a type of brain tumor. However, certain genetic conditions, like NF1, can make some families more likely to get this type of tumor. So, genetic testing could potentially be suitable for those families.

Most cases of pilocytic astrocytoma are caused by random genetic mutations, changes that happen by chance and aren’t passed down from parents to children.

Making sure individuals and their families understand the importance of detecting the tumor early and treating it promptly can make a big difference in how well they recover. Regular check-ups are very important to watch for any signs that the tumor is coming back and to manage any long-term impacts of the tumor or its treatment.

Patients should learn about symptoms like high pressure inside the skull and other changes related to the nervous system, so they can find medical help quickly if they notice these changes. Information on healthy living, helpful treatments outside of medicine, and resources can also be very supportive for people dealing with pilocytic astrocytoma and can improve their quality of life.