Hemangioblastoma is a slow-growing, noncancerous tumor made up of an unusually dense network of small blood vessels together with a population of large, pale-looking tumor cells. It is classified as a grade 1 tumor, the lowest grade, which means it does not spread to other parts of the body and does not turn into a more serious cancer over time.
Most hemangioblastomas develop in the central nervous system, particularly in the cerebellum at the back of the brain, in the brainstem, and in the spinal cord. They also occur at the back of the eye, in the retina. Less commonly, the same tumor arises outside the nervous system altogether, in places including the kidney, the soft tissue of the back and abdomen, the pancreas, the liver, and along peripheral nerves. Wherever it occurs, it is the same tumor with the same microscopic appearance and the same favorable outlook.
Because these tumors are benign, they cause problems mainly by pressing on nearby structures rather than by spreading. In the brain and spinal cord, where there is no room to expand, even a small tumor can cause significant symptoms. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.
Symptoms depend entirely on where the tumor is, and many hemangioblastomas cause none at all and are found on a scan done for another reason.
A small proportion of hemangioblastomas produce erythropoietin, a hormone that tells the bone marrow to make red blood cells. This can raise the red blood cell count enough to be noticed on a routine blood test, and the count returns to normal once the tumor is removed.
Hemangioblastoma is caused by loss of a gene called VHL. This gene normally makes a protein that senses how much oxygen a cell is receiving and switches off the cell’s oxygen-shortage response when oxygen is plentiful. When the gene is lost, that response stays permanently switched on, and the cell behaves as though starved of oxygen. It grows, and it signals for a dense new blood supply. This explains why hemangioblastomas contain so many blood vessels that the tumor is named for them.
The loss of the gene happens in one of two ways, and the difference matters a great deal:
This is one of the strongest links between a single tumor type and an inherited condition in all of pathology, and it has a direct practical consequence. Anyone diagnosed with a hemangioblastoma is generally offered genetic testing, regardless of age or family history. Certain features make an inherited cause more likely: a young age at diagnosis, more than one tumor, a tumor in the retina or spinal cord, or a family history of hemangioblastoma, kidney cancer, or adrenal tumors. Our article on von Hippel-Lindau syndrome explains what a positive result means.
Hemangioblastoma is uncommon, making up roughly 2% of all tumors arising inside the skull and around 2% to 10% of tumors of the spinal cord. In the cerebellum of an adult, however, it is one of the more frequent primary tumors. Hemangioblastomas arising outside the nervous system are genuinely rare, and most reports of them describe single cases.
Clinicians usually suspect hemangioblastoma on imaging before examining any tissue. On MRI, it has a characteristic appearance: a small, intensely enhancing nodule, often sitting in the wall of a much larger fluid-filled cyst. The cyst is not a tumor. It is fluid that has accumulated around the nodule, and it often causes most of the pressure and symptoms. Because the tumor is so rich in blood vessels, large feeding vessels often appear on the scan.
A pathologist confirms the diagnosis by examining tissue under a microscope. In most cases, this happens after the whole tumor has been removed, since these tumors bleed briskly and a needle biopsy carries more risk than usual. Retinal tumors are usually diagnosed by their appearance on eye examination and imaging, without taking any tissue.
Under the microscope, the tumor has two components sitting side by side. The first is a dense network of small, thin-walled blood vessels. The second is the tumor cells themselves, called stromal cells, which are large and pale with bubbly, foamy-looking cytoplasm because they are filled with tiny droplets of fat. Their nuclei can look irregular and dark, which is alarming at first glance but does not indicate cancer in this tumor. Cell division is rare, and areas of dead tissue are uncommon.
The main difficulty for the pathologist is that these pale, fat-filled cells resemble those of clear cell renal cell carcinoma, a kidney cancer that can spread to the brain. Distinguishing the two is critical, because one is a benign tumor cured by surgery and the other is metastatic cancer. The distinction is especially important in people with von Hippel-Lindau syndrome, who are at risk of both. A panel of special stains resolves this reliably, and the next section describes those results.
Immunohistochemistry uses antibodies to detect specific proteins inside cells. In hemangioblastoma, it confirms the diagnosis, particularly to separate this tumor from metastatic clear cell renal cell carcinoma. The two patterns are opposite, which makes the test dependable. Your report may list some or all of the following:
Ki-67 may also be reported. It measures how many tumor cells are actively dividing and is given as a percentage rather than as positive or negative. In hemangioblastoma, the figure is low, usually under 2%, consistent with a slow-growing grade 1 tumor.
Not every case requires every stain. When the appearance under the microscope is characteristic, and the tumor was removed from a typical location, the diagnosis can often be made without any of them, and a report listing only one or two is not incomplete.
Grade describes how a tumor is expected to behave. The World Health Organization grades central nervous system tumors from 1 to 4, and assigns a grade to the tumor type itself rather than deciding it case by case, as it is for many cancers elsewhere in the body.
Hemangioblastoma is CNS WHO grade 1, the lowest grade. This means it grows slowly, does not invade the surrounding brain or spinal cord, does not spread to other parts of the body, and does not become a higher-grade tumor over time. A grade 1 tumor that is completely removed is generally cured.
Grade 1 does not mean the tumor is harmless. In the brain and spinal cord, there is no spare room, so a slow-growing tumor in a critical location can cause serious and sometimes permanent problems. The grade describes the behavior of the tumor cells, not the seriousness of the situation, and location matters at least as much here.
Changes in the VHL gene are present in essentially all hemangioblastomas, whether or not the person has von Hippel-Lindau syndrome. Testing the tumor tissue alone therefore does not distinguish the two, and a report describing a VHL change in the tumor is an expected finding rather than evidence of an inherited condition.
Establishing whether the change is inherited requires a separate germline test on a blood or saliva sample, which examines the DNA a person was born with rather than the DNA of the tumor. A change found only in the tumor is called somatic, exists only in the tumor cells, and cannot be passed to children. Because a quarter to a third of hemangioblastomas turn out to be inherited, germline testing is generally recommended for everyone with this diagnosis.
No biomarker in this tumor predicts response to a particular drug. The genetic result matters for a different reason: it determines whether this is a single tumor or one feature of a condition that requires lifelong surveillance of several organs.
The prognosis is excellent. A hemangioblastoma that is completely removed is generally cured, and long-term survival after complete removal is very high. These tumors do not spread or become malignant.
The findings that matter most are:
That last point separates two quite different situations. In someone without the syndrome, completely removing a hemangioblastoma is usually the end of the matter. In someone with von Hippel-Lindau syndrome, this tumor is one event in a condition that requires lifelong surveillance.
Treatment of a hemangioblastoma that is causing symptoms is surgical removal, and complete removal is usually curative. Because these tumors are so vascular, surgery is planned carefully and is sometimes preceded by a procedure to block the feeding blood vessels. Where a cyst is present, draining it relieves pressure, but the nodule must be removed as well or the cyst refills.
Tumors found on a scan that are causing no symptoms are often watched rather than removed, particularly in people with von Hippel-Lindau syndrome, who may have several. Many remain stable for years. Focused radiation, delivered as stereotactic radiosurgery, is an option for tumors that are difficult to reach surgically or for people who have several.
An ophthalmologist treats retinal tumors with laser or freezing treatment while they are small, before they threaten vision.
For people with von Hippel-Lindau syndrome, a medication called belzutifan is now approved for hemangioblastomas of the brain and spinal cord that need treatment where immediate surgery is not required. It blocks the protein that accumulates when the VHL gene is lost, and it can shrink tumors in several organs at once without an operation.
Follow-up depends on the genetic result. Someone without the syndrome generally has imaging for a period after surgery and can then be discharged. Someone with von Hippel-Lindau syndrome enters a lifelong surveillance program covering the brain, spine, eyes, kidneys, adrenal glands, and pancreas, usually coordinated by a specialist center.