Paraganglioma (or extra-adrenal pheochromocytoma) is a rare type of neuroendocrine tumour that develops outside of the adrenal glands, which sit on top of the kidneys. These types of tumours develop from a specific type of chromaffin cell called paraganglia cells, which produce catecholamine hormones. These hormones, which include dopamine, epinephrine (adrenaline) and norepinephrine, are commonly referred to as the ‘fight or flight’ hormones.
Neuroendocrine cancers are a complex group of tumours that develop in the neuroendocrine system, which is responsible for regulating important bodily functions such as heart rate, blood pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreas, and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cells, which are responsible for receiving signals from the nervous system and producing hormones and peptides (small proteins) in response.
Paragangliomas are most commonly diagnosed in adults between the ages of 30 and 50. Hereditary paragangliomas are diagnosed equally in men and women; however, paragangliomas that develop without a family history have a higher incidence in women. It is important to note while it is more common in these demographics, anyone can develop this disease.
Types of Paragangliomas
There are two types of paragangliomas, which are categorised by the nerve cells they are associated with.
Sympathetic Paraganglioma
Sympathetic paragangliomas are functional tumours (tumours that produce and secrete hormones) that develop along the sympathetic chain in the body. The sympathetic chain consists of the bilateral nerves that run parallel to the spine from the base of the skull to the coccyx (bottom portion of the spine). The nerves in this chain are primarily responsible for the ‘fight or flight’ responses, such as sweat, reflexes and accelerated heart rate. These types of tumours generally have a higher rate of metastasis (cancer that spreads throughout the body) and tend to be highly symptomatic.
Parasympathetic Paraganglioma
Parasympathetic paragangliomas are non-functional tumours (tumours that do not produce and secrete hormones) that develop in the parasympathetic nerves of the body. The parasympathetic nerves are located in the brain and the sacral portion of the spine. The parasympathetic nerves act in contrast to the sympathetic nerves, and induce relaxation responses by slowing breathing and/or heart rate, lowering blood pressure and assisting in digestion and urination. These types of tumours are usually asymptomatic.
Treatment
If a paraganglioma is detected, it will be staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.
Cancers can be staged using the TNM staging system:
- T (tumour) indicates the size and depth of the tumour.
- N (nodes) indicates whether the cancer has spread to nearby lymph nodes.
- M (metastasis) indicates whether the cancer has spread to other parts of the body.
This system can also be used in combination with a numerical value, from stage 0-IV:
- Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue.
- Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
- Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localised cancer.
- Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
- Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advanced or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Grade I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
- Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
- Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.
Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment options for paragangliomas may include:
- Surgery to remove as much of the tumour as possible (will vary based on location).
- Radiation therapy, potentially including peptide receptor radionuclide therapy (PRRT).
- Chemotherapy.
- Hormone medications.
- Targeted therapies.
- Cryotherapy.
- Watch and wait.
- Clinical trials.
- Palliative care.
For more information on treatment options, please refer to the Rare Cancers Australia Treatment Options page.
Risk factors
The risk factors for paragangliomas are often associated with having certain medical conditions, including:
Other risk factors for this disease include:
- Family history of paragangliomas and/or pheochromocytomas.
- Chronic hypoxia (most commonly found in people living at high altitudes).
- Mutations of the succinate dehydrogenase (SDH) gene.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
Parasympathetic paragangliomas are often asymptomatic and can be misdiagnosed or go undetected.
Sympathetic paragangliomas may present with some of the following symptoms:
- High blood pressure (hypertension).
- Headaches.
- Unexplainable sweatiness.
- Accelerated heart rate.
- Shakiness.
- Being very pale.
- Anxiety.
- Heart palpitations.
Not everyone with the symptoms above will have cancer but, see your GP if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have a paraganglioma, they will order a variety of diagnostic tests to confirm the diagnosis, and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Endocrine studies & blood tests
Endocrine studies involve blood and/or urine tests and imaging tests (see below) to analyse your hormone levels and detect any abnormalities. Some of these tests may include:
- General blood test to assess overall health.
- Blood catecholamine studies, which measure levels of certain catecholamine levels in your blood.
- 24-hour urine test, which measures levels of catecholamine levels in your urine.
Imaging tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), ultrasounds, and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and look for signs of metastasis. Your doctor may also recommend a somatostatin receptor scintigraphy scan, which involves injecting a radioactive substance into the bloodstream which attaches to the tumour and shows where the tumour(s) are located in the body.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage paragangliomas have good prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.