Paraganglion Neoplasm

Paraganglion neoplasm, commonly called paraganglioma, is a rare tumor that forms near major blood vessels and nerve pathways, most often in the neck, head, abdomen, or chest. While most of these tumors are not cancer, they can produce hormones that cause serious health problems like high blood pressure, rapid heartbeat, and severe headaches.

Table of contents

• What is Paraganglioma?
• Causes and Genetic Factors
• Symptoms
• Who is Affected?
• How Paraganglioma is Diagnosed
• Treatment Options
• Outlook and Follow-up

extra-adrenal pheochromocytoma, chemodectoma, carotid body tumor, glomus cell tumour

What is Paraganglioma?

A paraganglioma is a rare neuroendocrine tumor (a growth that forms from cells that make and release hormones) that develops near certain blood vessels and nerves outside of the adrenal glands^[1]. The adrenal glands are small organs that sit on top of the kidneys and produce important hormones that control heart rate, blood pressure, and how the body responds to stress^[1].

Even though paragangliomas don’t form in the adrenal glands themselves, they are made of tissue similar to what is found in the adrenal glands^[1]. These tumors are made of special cells called chromaffin cells, which can produce and release hormones known as catecholamines^[1]. The main catecholamines include dopamine, epinephrine (also called adrenaline), and norepinephrine (also called noradrenaline)^[1].

Paragangliomas most often develop along the sympathetic nervous system, which includes the area near the major blood vessels in the neck (particularly the carotid artery), along nerve pathways in the head and neck, and in the abdomen and chest^[2]. About 85% of paragangliomas are found in the abdomen, 12% in the chest, and only about 3% in the head and neck^[4].

Paragangliomas that form in the head and neck often develop from parasympathetic nerve tissue and usually don’t make extra hormones. These are sometimes called “biochemically silent” tumors^[4]. However, they can still cause symptoms by pressing on nearby structures, such as problems with hearing, vision, swallowing, or a pulsing sound in the ears^[4].

Is Paraganglioma Cancer?

Most paragangliomas are benign, meaning they are not cancer^[1]. Approximately 20% of paragangliomas are malignant (cancerous)^[1]. It can be very difficult for doctors to tell if a paraganglioma is cancerous just by looking at the tumor tissue under a microscope^[1]. Because of this challenge, a paraganglioma is usually considered cancer if it has spread to nearby tissues, spread to distant areas like the lungs or bones, or has come back after treatment^[1].

Approximately 35% to 50% of malignant paragangliomas may spread to other parts of the body^[3]. Paragangliomas in the head and neck are less likely to spread than tumors found in the chest, abdomen, or pelvis^[4].

How Paraganglioma Differs from Pheochromocytoma

Paraganglioma and pheochromocytoma are both rare tumors that form from the same type of chromaffin cells. The main difference is where they develop in the body^[1]. Pheochromocytomas form in the center of the adrenal gland, while paragangliomas form outside the adrenal gland^[1]. Some doctors refer to paragangliomas as extra-adrenal pheochromocytomas^[1].

Causes and Genetic Factors

Paragangliomas often don’t have a clear cause^[2]. There are no known environmental, dietary, or lifestyle risk factors that have been linked to developing paraganglioma^[5]. The only known risk factor is having a family history of these tumors^[8].

About 75% of paragangliomas occur randomly without any inherited pattern (called sporadic cases), while the remaining 25% are hereditary, meaning they run in families^[6]. People with hereditary paraganglioma have an increased likelihood of developing multiple tumors and of being diagnosed at a younger age^[6].

Scientists have found changes (mutations) in approximately 20 different genes that may lead to paraganglioma^[3]. The most commonly involved genes include SDHD, SDHAF2, SDHC, SDHB, and SDHA, which are related to a protein called succinate dehydrogenase^[6].

Genetic Conditions Associated with Paraganglioma

Several inherited genetic conditions are associated with an increased risk of developing paraganglioma^[3]:

• Multiple Endocrine Neoplasia Type 2 (MEN2A and MEN2B), caused by changes in the RET gene
• Von Hippel-Lindau syndrome, caused by changes in the VHL gene
• Neurofibromatosis type 1, caused by changes in the NF1 gene
• Hereditary paraganglioma syndrome, caused by changes in succinate dehydrogenase genes
• Carney-Stratakis syndrome
• Carney triad

Many of these genetic conditions are inherited in a pattern called autosomal dominant, which means that children of affected parents have a 50% chance of inheriting the genetic change^[8].

Who Should Consider Genetic Testing?

Doctors recommend genetic testing for people who have^[8]:

• Multiple paragangliomas
• A family history of paraganglioma or related tumors
• A family history of the genetic syndromes mentioned above
• Signs or symptoms of these genetic syndromes
• Been diagnosed before age 30

If you are diagnosed with paraganglioma, it’s important to talk to your doctor about genetic testing^[4]. Genetic counseling is an important part of the treatment plan for patients with paraganglioma^[11]. Family members should have genetic testing only if the patient is found to have a genetic mutation^[8].

Symptoms

Many paragangliomas don’t cause any symptoms, especially those that don’t produce extra hormones^[2]. Some paragangliomas are found by accident during medical tests for other reasons^[4].

When symptoms do occur, they depend on where the tumor is located and whether it is producing extra hormones^[2].

Symptoms from Tumors in the Head and Neck

Paragangliomas in the head or neck can cause symptoms by pressing on nearby structures^[2]:

• A rhythmic pulsing or whooshing sound in the ears (called pulsatile tinnitus)
• Trouble swallowing
• Hoarse voice
• Hearing loss
• Blurred vision
• Dizziness
• Swelling or a lump in the neck

Symptoms from Hormone-Producing Tumors

When paragangliomas produce extra catecholamines (hormones like adrenaline), they can cause symptoms throughout the body^[1]:

• High blood pressure (hypertension), which may be constant or come and go in episodes
• Severe headaches
• Rapid or pounding heartbeat (palpitations)
• Heavy sweating
• Anxiety or feeling nervous
• Pale skin or flushing
• Shaking or tremors

These symptoms may occur in episodes called “spells” that can happen weekly, several times daily, or once every few months^[4]. Most episodes last less than an hour^[4]. Spells may occur on their own or may be triggered by certain activities^[4].

Less common symptoms may include^[4]:

• Vomiting and nausea
• Abdominal or back pain
• Fatigue and weakness
• Shortness of breath
• High blood sugar
• Extreme weight loss

Because paragangliomas can release adrenaline in uncontrolled bursts, they can cause serious health problems like stroke, heart attacks, and even death^[8]. For this reason, some doctors call it a “pharmacologic time bomb”^[8].

Who is Affected?

Paraganglioma is very rare. It’s estimated that only 2 out of every 1 million people develop paraganglioma^[1].

Anyone at any age can get a paraganglioma, but they occur most often in people between 30 and 50 years of age^[1]. The average age at diagnosis is 24.9 years in hereditary cases and 43.9 years in sporadic (non-inherited) cases^[5]. Approximately 10% of cases occur in children^[1].

Paragangliomas affect men and women equally^[4].

How Paraganglioma is Diagnosed

Diagnosing paraganglioma often starts with recognizing symptoms, though some people have no symptoms at all^[3]. The journey from symptoms to diagnosis can sometimes be long, and patients may feel dismissed by their medical team^[4].

Blood and Urine Tests

If your doctor suspects paraganglioma, they will order blood and urine tests to check the levels of hormones in your body^[3]. These tests can detect extra catecholamine hormones (like adrenaline and noradrenaline) that may be produced by a paraganglioma^[9]. The tests may also look for other clues, such as a protein called chromogranin A^[9].

Imaging Tests

Your doctor will use imaging scans to look at where the tumor is, how big it is, and to check for signs that the tumor has spread to other parts of the body^[3]. Several types of imaging tests may be used^[9]:

• Magnetic resonance imaging (MRI) uses radio waves and a magnetic field to make detailed images
• Computed tomography (CT) scan combines a series of X-ray images taken from various angles
• Metaiodobenzylguanidine (MIBG) scan detects an injected radioactive tracer that is absorbed by paragangliomas
• Positron emission tomography (PET) scan also detects a radioactive tracer absorbed by tumors

Genetic Testing

If you have a paraganglioma, your healthcare provider may recommend genetic testing to look for DNA changes in your body that are passed from parents to children^[9]. Results of genetic testing can help predict the chances of your tumor coming back after treatment^[9]. Your parents, children, or siblings may also be checked for DNA changes that raise the risk of paragangliomas^[9].

Treatment Options

Treatment of paraganglioma may involve many different doctors, including specialists in hormone disorders, surgeons, and doctors who diagnose and treat neuroendocrine tumors^[3]. Once diagnosed, it is recommended to be seen by a team of specialists with experience in treating paraganglioma^[4].

Recommendations for treatment depend on the size and location of the tumor, how fast it’s growing, and details of your overall health^[7].

Medications

Before any other treatment, your doctor may give you medications to control symptoms caused by extra hormones^[3]. These may include alpha blockers followed by beta blockers, which are drugs used to control high blood pressure^[3].

Active Surveillance (Watch and Wait)

If you have a small tumor that isn’t causing symptoms, your doctor may recommend periodic MRI imaging and physical exams without other treatments^[7]. In some cases, the tumor grows very slowly, and it may be safest for your doctor to check your tumor regularly without treating it^[3].

Surgery

If possible, the treatment of choice for paraganglioma is surgery to remove the tumor^[4]. Once paraganglioma is diagnosed, you may have surgery to remove the tumor^[3]. The extent of surgery depends on the tumor location^[7]. Surgery for tumors near the middle ear might involve only a brief outpatient procedure, while surgery for tumors on major blood vessels may require inpatient surgery and a period of recovery in the intensive care unit^[7].

Surgery is sometimes performed along with a procedure called embolization, which cuts off the blood supply that helps feed the tumor^[7]. Sometimes surgery is not an option, in which case your doctor will discuss other options with you^[3].

Surgical treatment usually alleviates symptoms^[4].

Radiation Therapy

Radiation therapy can be used to slow the tumor from growing and to help relieve symptoms^[3]. A form of radiation therapy called stereotactic radiosurgery or CyberKnife may be recommended^[7]. This is a robotic system that delivers precise pulses of high-dose radiation to the target tissue while limiting exposure to surrounding healthy tissues^[7]. Radiation cannot remove the tumor, but it can be very effective at stopping its growth^[7].

Combination Treatment

Many paragangliomas may be treated with a combination of active surveillance, surgery, and radiation therapy^[7].

Outlook and Follow-up

Paragangliomas usually grow very slowly, though this can vary from case to case^[1]. If detected early, paragangliomas can be successfully treated and managed in the vast majority of cases^[4].

Long-term follow-up is recommended for all individuals with paraganglioma because there is no test that can completely determine whether a tumor is benign or malignant^[6]. Even after the tumor is removed, it can sometimes be impossible to tell the difference between a malignant and benign paraganglioma under the microscope^[8]. The only definite way to tell if it is malignant is if there is spread to nearby organs, spread to distant sites like the lungs or bones, or if the cancer comes back^[8].

The challenges of cancer extend far beyond treatment, and recovery involves emotional healing as well^[20]. Finding support networks and connecting with other people who have experienced paraganglioma can be helpful for healing^[20].