Hemangioblastoma

What is Hemangioblastoma?

Hemangioblastomas are uncommon, non-cancerous tumors that contain many blood vessels. They are mostly found in the part of the brain called the cerebellum. However, they can also occur in the spine and brainstem. While these tumors can simply occur on their own, they also might be related to a genetic disorder called von Hippel-Lindau (VHL) disease. This disorder increases the risk of developing certain types of tumors. Around 45% of people with VHL disease also have these particular brain tumors, while an estimated 20% of people with these brain tumors have VHL. Although rare, hemangioblastomas represent 1% to 2.5% of all brain tumors and 2% to 10% of spine tumors. They usually appear between the ages of 30 and 60 and tend to be slightly more common in men.

The symptoms of hemangioblastomas can vary depending on where the tumor is. Hemangioblastomas in the cerebellum often cause headaches, feel like you might vomit, or cause vomiting. They can also increase the pressure inside your skull. If the tumor is in the brainstem, it can cause issues with your ability to move and feel sensations, unsteady movements and potentially dangerous bleeding. Spinal hemangioblastomas can cause pain in the area of the tumor, weakness, unusual sensations, and affect the control of your bowels or bladder.

The main way to diagnose these tumors is using a type of scan called an MRI. This usually shows a mass in your body filled with fluid that has a part that enhances when a particular dye is used. The first line of treatment is surgery to remove the tumor. Sometimes, a procedure to block the blood supply to the tumor might be necessary before surgery because the tumor has so many blood vessels. Other forms of treatment that are gaining interest include focused forms of radiation treatment and new drugs that target a particular pathway involved in blood vessel growth.

The outlook after surgery is generally good, with the tumors coming back in under 25% of cases. However, regular check-ups are important, especially for those with VHL disease.

What Causes Hemangioblastoma?

Hemangioblastoma, a type of brain tumor, can occur randomly (in 75% of cases) or as a part of VHL disease. VHL disease happens due to an inherited gene mutation in the VHL gene. This type of gene mutation is passed down in a way that if a parent has the mutation, there’s a 50% chance their child will too.

However, in cases where hemangioblastoma occurs randomly, changes in the VHL gene and other genetic irregularities have been found. The VHL gene, which helps suppress tumor formation, is located on a specific part of our chromosomes and produces a protein consisting of 213 units named as pVHL.

Different types of changes in this VHL gene are noted, such as missense (changing one unit in a gene), mutations that affect where the gene is split during protein formation, and frameshift mutations that happen when more genetic units are removed than added. Changes can also occur due to ‘gene silencing’, which is when the normal function of a gene is blocked due to methylation—a biological process where small molecules latch onto the gene.

It’s been noticed that changes to or deletion of the VHL gene is more common in hemangioblastomas associated with VHL disease. Promoter methylation, on the other hand, has only been found in random cases of hemangioblastoma.

In addition, even when there’s no VHL gene mutation, loss of genetic material in specific chromosomes has been discovered in random cases. This suggests that there could be other ways in which the disease develops in these instances.

Risk Factors and Frequency for Hemangioblastoma

Hemangioblastomas are a kind of tumor, responsible for around 1-2.5% of all tumors in the brain and 2-10% of primary tumors in the spinal cord. The rate of occurrence for this tumor in the central nervous system (CNS) is around 0.141 for every 100,000 people each year. This makes them quite rare, with only about 1 in a million people estimated to develop a hemangioblastoma yearly. These tumors are mostly diagnosed in adults aged 30-65 and are slightly more common in men.

• Hemangioblastomas account for 1-2.5% of all brain tumors and 2-10% of primary spinal cord tumors.
• The overall rate of these tumors in the CNS is approximately 0.141 per 100,000 people per year.
• These tumors are rare, with an estimated one in a million people developing hemangioblastomas each year.
• They are mostly diagnosed in adults between the ages of 30 and 65.
• There is a slight predominance of these tumors in males.

These tumors can develop anywhere in the CNS but are most commonly found in the back part of the brain called the posterior fossa, especially in the cerebellum. About 45-50% of these tumors are found in the cerebellum, 30-40% in the spinal cord, and 5-10% in the brainstem. When someone has a single hemangioblastoma, it’s usually in the cerebellum, but people with a condition called VHL can have multiple lesions in the spinal cord, cerebellum, and brainstem.

• Most hemangioblastomas are located in the posterior fossa of the brain, with the cerebellum being the most common site.
• About 45-50% of these tumors are found in the cerebellum, 30-40% in the spinal cord, and 5-10% in the brainstem.
• Single hemangioblastomas are most often found in the cerebellum.
• Individuals with VHL may have multiple lesions in the spinal cord, cerebellum, and brainstem.

Signs and Symptoms of Hemangioblastoma

When a patient comes in with suspected hemangioblastoma, a kind of brain tumor, the doctor starts by taking a full health history and doing a complete physical examination. These tests will help the doctor determine if there’s a problem inside the skull.

How the illness shows up in a patient depends on where the tumor is in the brain and what nearby areas might be affected. Symptoms start to appear when these slow-growing tumors have grown big enough to interfere with the function of the area around them. The most common location for these tumors is at the back of the brain, which leads to blockage of the fluid-filled channels in the brain and increased pressure inside the skull. This increased pressure often results in symptoms like headaches and throwing up. Along with this, patients might feel dizzy, might have problems with balance and coordination, and could have gait disturbances.

A thorough review of the patient’s family history is also important to identify any signs of a possible genetic connection. Doctors look for a history of certain kinds of tumors that are associated with von Hippel-Lindau (VHL) syndrome, a genetic disorder that can also cause hemangioblastomas. The history might reveal the presence of tumors on the back of the eye, kidney cancer, pheochromocytomas (tumors of the adrenal gland), and pancreatic neuroendocrine tumors. The history might also reveal a past surgery on the patient or a family member to remove a tumor related to VHL syndrome.

In the physical examination, doctors look for signs of increased pressure inside the skull and the presence of a mass effect, which refers to the pressure a tumor can exert on surrounding structures. Additional physical examination findings will depend on where the tumor is located inside the central nervous system.

• Ataxia: This could cause problems with balance and coordination, leading to difficulty walking and performing delicate actions.
• Dysmetria: This can be tested using finger-to-nose or heel-to-shin tests and is mainly found with tumors located in the portion of the brain responsible for coordination and balance.
• Nystagmus: This refers to involuntary eye movements, which can suggest the involvement of the cerebellum or brainstem.
• Back pain: There might be localized or shooting back pain that follows the path of the affected nerve roots.
• Motor weakness and myelopathy: The muscles served by the affected area of the spine might be weak.
• Sensory disturbances: The patient might lose sensation or feel weird sensations in areas of the body served by the affected area of the spine.

Still, it’s important to remember that patients with VHL disease need to undergo a full-body examination to identify other signs of the syndrome, which could include:

• Abdominal examination: This is done to find any masses that could suggest the presence of kidney or pancreatic tumors.
• Ophthalmologic examination: The doctor will check for lesions on the back of the eye.
• Endocrine evaluation: This is to look for signs of pheochromocytoma, like high blood pressure, heart palpitations, and occasional headaches.

Testing for Hemangioblastoma

If your doctor suspects you may have a tumor, they will use various methods to determine the best way to image, or “see,” the suspected tumor.

One of the best ways to diagnose a specific type of tumor, called CNS hemangioblastomas, is by using Magnetic Resonance Imaging (MRI). An MRI works by using magnetic fields and radio waves to produce detailed images of the inside of your body. This particular tumor often shows up in MRIs as a well-defined, round spot within a fluid-filled sac. These round spots may appear darker or the same color as the surrounding tissue and often shine very brightly when a contrast material, containing a substance called gadolinium, is given to the patient. This contrast material helps to highlight the tumor, making it easier to see.

Another helpful imaging technique is Computed Tomography, better known as a CT scan. A CT scan uses x-rays to produce images of slices, or “sections,” of your body. In the case of hemangioblastomas, the round tumor appears the same color as the brain noncontrast images, surrounded by fluid from the cyst. After contrast is given, the tumor shines brightly on the scan.

In some cases, a procedure called an angiography is used to get a better look at the blood vessels feeding the tumor. Hemangioblastomas are often supplied by enlarged blood vessels, which can be seen during an angiography. This process involves injecting a dye into your blood vessels and then taking x-rays.

In addition to imaging, laboratory tests are often used to assess a patient’s overall health and preparedness for possible surgery. These tests can include a complete blood count, liver function tests, kidney function tests, and coagulation profiles, which measure how quickly your blood clots. If your doctor suspects the hemangioblastoma is connected to a condition called Von Hippel Lindau disease, they may recommend genetic testing to look for a specific gene mutation.

Treatment Options for Hemangioblastoma

Surgery is usually the best treatment for a type of brain tumor called CNS hemangioblastoma, especially if it’s causing symptoms due to the pressure it’s putting on the brain (a mass effect). The goal of surgery is to remove the entire tumor while causing as little damage as possible to the surrounding brain. These tumors have a lot of blood vessels, so it’s important to plan the surgery in detail to reduce bleeding. Treatments to block the tumor’s blood supply can also be done before surgery to make it safer and easier. The most common way to access these tumors surgically is through a procedure called a suboccipital craniotomy, which allows surgeons excellent access to remove the tumor. Advanced tools like microscopes are used to help remove the tumor, and techniques to monitor the nervous system can help preserve its function during surgery. Systems that use imaging to guide the surgery may also be used to improve accuracy.

In terms of medical treatment, these tumors are usually managed with supportive care, as they’re benign lesions that do not invade surrounding structures or spread to other sites in the body (metastasize). So, chemotherapy has a limited role. However, several new types of drugs, particularly those that stop the growth of blood vessels (antiangiogenic factors), have shown promise, especially in patients with mutations in the VHL gene. Medications that target vascular endothelial growth factor, a protein that stimulates blood vessel growth, have been investigated for their ability to stop tumor growth by reducing blood vessel formation. Other drugs, known as tyrosine kinase inhibitors, have also shown promise in this area.

Another treatment option called stereotactic radiosurgery (SRS) uses high doses of radiation to precisely target the tumor while sparing healthy tissue around it. This approach can be especially helpful for small tumors that are hard to reach surgically or leftover tumors after surgery. Different types of equipment, such as Gamma Knife and CyberKnife, can be used to perform SRS.

After treatment, it’s crucial to monitor the brain regularly using MRI scans to check for any signs that the tumor might be growing back or getting worse. The frequency of these follow-up scans depends on the initial tumor characteristics, including how much of the tumor was removed and whether there’s a mutation in the VHL gene. Generally, scans are done every six to twelve months for the first few years after surgery, then annually if there’s no sign of recurrence.

For patients with VHL disease, it’s important to monitor regularly for the risk of the tumor coming back or new ones appearing. This usually involves regular imaging as well as eye exams to check for retinal hemangioblastomas, another type of tumor associated with VHL. Genetic counseling and testing are recommended for patients and their families to identify those at risk and start monitoring them early.

What else can Hemangioblastoma be?

Metastatic brain tumors, especially those originating from the kidney (renal cell carcinoma), can appear similar to a type of brain tumor called hemangioblastomas, particularly in the back section of the brain. These tumors often present as very distinct, blood-rich lesions with certain cellular characteristics. Further testing such as immunohistochemical staining is required to identify the differences between the two. This is because hemangioblastomas usually exhibit certain proteins (alpha-inhibin and S100), while renal cell carcinomas show other markers.

Pilocytic astrocytoma is another benign tumor often found in children and young adults, which can also resemble hemangioblastomas due to its cystic and solid components. Despite their similarities, pilocytic astrocytomas have certain markers, such as Rosenthal fibers and eosinophilic granular bodies, which are not present in hemangioblastomas. By additionally using immunohistochemical staining, it can help further differentiate these two.

Ependymomas, tumors that originate from the lining of the fourth brain ventricle, may also be confused with hemangioblastomas due to their similar location and appearance. However, specific structures can differentiate ependymomas from hemangioblastomas. Ependymomas also express certain markers, which are not found in hemangioblastomas.

Vascular conditions like arteriovenous malformations and cavernous malformations can also imitate these tumors due to their highly vascular nature. Special imaging tests can help in identifying these vascular abnormalities.

Other cystic lesions in the brain and spinal cord such as arachnoid cysts and neuroenteric cysts should also be considered as potential alternatives when diagnosing in the cerebellum. Arachnoid cysts are benign, fluid-filled sacs that arise within the arachnoid membrane and are usually symptom-free unless they grow large and cause symptoms related to pressure on other structures. Unlike hemangioblastomas, they do not show up on contrast on MRIs. Neuroenteric cysts are rare congenital lesions that also appear cyst-like but have distinct cellular features.

What to expect with Hemangioblastoma

The outlook for patients with hemangioblastoma, a type of brain tumor, relies on a variety of factors. These include where the tumor is located in the brain, the size of the tumor when it’s discovered, and whether it’s associated with a rare disease called Von Hippel-Lindau (VHL) disease or not.

How well the surgery goes and how much of the tumor is removed can also impact the patient’s outlook. For hemangioblastomas that are sporadic – meaning they appear without any connection to a genetic condition – the outlook is generally very good after surgical removal. These tumors grow slowly, and complete removal usually results in long-term survival without the disease coming back. Studies indicate that patients with sporadic hemangioblastomas usually have a very high long-term survival rate, with over 90% surviving 5 years after their diagnosis.

The outlook for patients with VHL is a bit more complicated. This is because these patients can also have other types of tumors like kidney cancer, pheochromocytoma (an adrenal gland tumor), and pancreatic tumors. If patients with VHL develop involvement of the central nervous system – essentially, if their brain or spinal cord is affected – their outlook tends to be worse.

Possible Complications When Diagnosed with Hemangioblastoma

Hemangioblastomas, or tumors in the brainstem or cerebellum, can block fluid pathways in the brain and cause a condition called hydrocephalus. This often requires further surgery, like a ventriculoperitoneal shunt or third ventriculostomy. Depending on their location, these tumors can cause different neurological symptoms:

• Cerebellar tumors can cause symptoms related to the cerebellum
• Spinal cord tumors can lead to motor weakness and sensation problems
• Brainstem tumors can affect the cranial nerves and result in facial weakness, difficulty swallowing, and double vision

Removing hemangioblastomas surgically is risky because these tumors have a rich blood supply, leading to potential significant bleeding during surgery. Preoperative embolization, or blocking the blood vessels that feed the tumor before surgery, can reduce but not completely remove this risk. Complete removal of the tumor can be especially difficult in critical areas like the brainstem and spinal cord, and can result in complications after surgery, like new or worsening neurological deficits. Surgery in the posterior fossa (an area at the back of the brain) also carries the risk of cerebrospinal fluid leaking, which can lead to meningitis if not managed promptly. To prevent these complications, proper surgical closing techniques and careful monitoring after surgery are necessary.

People with VHL disease are at high risk for developing multiple lesions and recurring tumors, which may require regular MRI monitoring and possible repeated surgeries. This disease also poses a risk for other types of tumors like pheochromocytomas, renal cell carcinoma, and pancreatic neuroendocrine tumors. This can lead to complications like high blood pressure and kidney dysfunction. Managing these issues requires a team of healthcare professionals. The ongoing condition and regular surveillance often affects patients’ quality of life so psychological support and rehabilitation services are vital.

Preventing Hemangioblastoma

As with any medical condition, it’s really important for patients with von Hippel Landau disease to understand their disease well. Patients need to know that this is a serious condition and that it has a genetic component. This means that they are more likely to develop tumors in different parts of their body because of inherited factors.

Having regular MRI scans and other imaging tests is crucial because they can help doctors keep an eye on any tumors. Early identification and treatment can make a huge difference. So, it’s important that patients have plenty of information about their disease, as well as the genetic aspect of their condition. This will enable them to pick up on any symptoms earlier and to make plans for their future. For instance, they might want to get genetic counseling before deciding to start a family.