Paraganglioma (or extra-adrenal pheochromocytoma) is a rare type of neuroendocrine tumoura tissue mass that forms from groups of unhealthy cells 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 cellsthe basic structural and functional unit of all living things, 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, bloodthe red bodily fluid that transports oxygen and other nutrients around the body pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreasa long, flat organ that sits between the stomach and the spine that plays a key role in digestion and blood sugar regulation, 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 tumourstumours that produce and secrete hormones that develop along the sympathetic chain in the body. The sympathetic chain consists of the bilateralaffecting both sides 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 metastasiswhen the cancer has spread to other parts of the body, also known as mets, and tend to be highly symptomatic.
Parasympathetic Paraganglioma
Parasympathetic paragangliomas are non-functional tumourstumours 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, and how the cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas 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 (nodea small lump or mass of tissue in your body) indicates whether the cancer has spread to nearby lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid.
- 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 tissuea group of cells that work together to perform a function.
- 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 localisedaffecting only one area of body 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 advancedat a late stage, far along or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 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 testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, 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:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour as possible (will vary based on location).
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells, potentially including peptide receptor radionuclide therapy (PRRT)a targeted cancer treatment that uses radioactive substances (radionuclides) to deliver radiation directly to tumour cells.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Hormone therapymedication that alters the levels of certain hormones in the body, such as oestrogen and progesterone.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Cryotherapythe process of freezing off cancerous tumours and/or lesions using liquid nitrogen.
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Risk factors
The riskthe possibility that something bad will happen factors for paragangliomas are often associated with having certain medical conditions, including:
- Multiple endocrine neoplasia 2 syndrome (MEN2A and MEN2B).
- Von Hippel-Lindau (VHL) syndrome.
- Neurofibromatosis type 1 (NF1).
- Hereditary paraganglioma syndrome.
- Carney-Stratakis dyad.
- Carney triad.
Other risk factors for this disease include:
- Family history of paragangliomas and/or pheochromocytomas.
- Chronica long-lasting disease that changes slowly over time 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.
Some of the information regarding risk factors was obtained from the Paraganglioma page published by the National Cancer Institute.
Symptoms
Parasympathetic paragangliomas are often asymptomatic and can be misdiagnosed or go undetected.
Sympathetic paragangliomas may present with some of the following symptoms:
- Hypertensionhigh blood pressure.
- Headaches.
- Unexplainable sweatiness.
- Tachycardiaa rapid heart rate; clinically defined as a rate of more than 100 beats per minute.
- 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
If your doctor suspects you have a paraganglioma, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Endocrine studiesstudies that involve blood, urine and/or imaging tests to analyse hormone levels.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
