Paraganglioma of the Head and Neck

Introduction:

Paragangliomas are a neuroendocrine type of tumor that develops near clusters of nerve cells called ganglia. A majority of paragangliomas involve nerve cells called chromaffin cells. Tumors that arise in the adrenal glands (a gland that produces adrenaline and noradrenaline) are called pheochromocytomas, and those that occur elsewhere in the body are called paragangliomas. Paragangliomas are usually benign (noncancerous), but certain paragangliomas can transform into malignant (cancerous) tumors and metastasize (spread) to other parts of the body. In the head and neck region, paragangliomas develop near the major blood vessel called the carotid artery and along the nerve pathways.

What Are Paragangliomas Composed Of?

Paragangliomas are composed of a certain type of cell called the chromaffin cells, which manufacture and release hormones called catecholamines. Adrenal glands are glands that are present on the top of each kidney. These produce several hormones, of which catecholamines help control certain functions like:

• Blood pressure.

• Heart rate.

• Blood glucose levels.

• Response of the body to stress.

The major catecholamines are dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline). Though paragangliomas do not develop in the adrenal glands, they are composed of tissues that are present in the adrenal glands. Paragangliomas may let out extra catecholamines into the blood, which can cause certain signs and symptoms.

How Common Are Paragangliomas and Who Is Affected?

Paraganglioma is an uncommon tumor, and it is estimated that only two out of every 1 million people have this tumor. Any individual at any age may be affected by paraganglioma, but it occurs most commonly in individuals between 30 and 50 years of age. About 10 % of the affected cases involve children.

How Does Paraganglioma Differ From Pheochromocytoma?

Paraganglioma and pheochromocytoma are rare types of tumors originating from the same type of cells called chromaffin cells. The difference lies in where these tumors originate in the body. Pheochromocytomas develop in the center of the adrenal gland in the adrenal medulla. In contrast, paragangliomas develop outside the adrenal gland, mostly along the nerves and arteries in the head and neck region. Paragangliomas are also referred to as extra-adrenal pheochromocytomas.

Does Paraganglioma Have the Potential to Turn Into a Cancerous Condition?

Paragangliomas are usually benign (non-cancerous), but about 20 % of the paragangliomas can be malignant (cancerous). It can be difficult for healthcare professionals to determine if the paraganglioma is cancerous or not, even after examining the tumor tissue under a microscope. Due to this, a paraganglioma is considered cancerous if it shows the following features:

• Metastasizes (spreads) to neighboring tissues (regional spread).

• Metastasizes to distant regions like the bones or lungs.

• Shows recurrence.

What Are the Types of Paragangliomas?

Paragangliomas can be classified as follows:

• Localized Paraganglioma: The tumor is localized and present only in one region.

• Regional Paraganglioma: In this type, the paraganglioma has either spread to the neighboring tissues or to the lymph nodes.

• Metastatic Paraganglioma: In this type, the tumor metastasizes to other body parts like the bones, liver, lungs, or distant lymph nodes. About 35 % to 50 % of malignant paragangliomas may metastasize to other body parts.

• Recurrent Paraganglioma: The recurrence of the paraganglioma, even after treatment, is called recurrent paraganglioma. The recurrence can occur at the same site or in other body parts.

What Are the Causes of Paraganglioma?

Scientists believe that mutations in about 20 different genes can result in the occurrence of paraganglioma and pheochromocytoma. These genes include RET, VHL, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2, MDH2, IDH1, PHD1/PHD2, HIF2A/EPAS1/2, TMEM127, MAX, HRAS, MAML3 and CSDE1. Certain other genetic conditions like neurofibromatosis (tumors that develop in the nervous system), hereditary paraganglia syndrome, and so on can also cause paraganglioma.

What Are the Signs and Symptoms of Paraganglioma?

The signs and symptoms of paraganglioma appear when the tumor lets out excessive adrenaline or noradrenaline into the blood. A few paragangliomas that do not produce extra adrenaline or noradrenaline are asymptomatic. Common signs and symptoms of paragangliomas are as follows:

• Hypertension (high blood pressure).

• Feeling shaky.

• Headaches.

• Loss of hearing.

• Ringing in the ears.

• Difficulty swallowing.

• Pain.

• Excessive sweating that occurs for no reason.

• A fast, pounding, or irregular heartbeat.

Less common symptoms include:

• Nausea and vomiting.

• Paler than usual.

• Constipation.

• Diarrhea.

• Hyperglycemia (elevated blood glucose levels).

• Unexplained weight loss.

• An intense drop in blood pressure when one stands suddenly (orthostatic hypotension).

In a few individuals, the symptoms may not be frequent or can occur in bursts lasting less than an hour but persist for several days.

How Can Paraganglioma Be Diagnosed?

Paraganglioma can be diagnosed in the following ways:

• Physical Examination: In this, the overall health, medical history, family history, and blood pressure of the individual will be assessed.

• 24-Hour Urine Test: Urine samples are collected for 24 hours to measure the levels of catecholamines (adrenal hormones) in the urine. Elevated values may indicate the presence of paraganglioma.

• Blood Catecholamine Tests: The level of catecholamines in the blood is measured in these tests. Substances formed from the breakdown of these hormones are also evaluated.

• Positron Emission Tomography (PET): This test is useful in detecting the location of the paragangliomas.

• Computed Tomography (CT) Scan: This test is also useful in localizing the location of the tumor.

• Magnetic Resonance Imaging (MRI): In this diagnostic procedure, a large magnet, a computer, and radio waves are used to produce two and three-dimensional pictures of the soft tissue organs in the body.

How Can Paragangliomas Be Treated?

The treatment depends on the size, nature (cancerous or non-cancerous), symptoms, metastasis (spread), and whether the tumor has developed for the first time or whether it has recurred. Paragangliomas that cause symptoms due to the excessive release of adrenal hormones are managed through medications. These medications are as follows:

• Alpha-blockers (to regulate blood pressure).

• Beta-blockers (to normalize the heart rate).

• Medications that inhibit the effects of excess hormones released by the adrenal gland.

Other treatment options include:

• Surgery and Removal of Tumor: Surgery is the primary treatment modality for paragangliomas. The surrounding tissues are checked for metastasis during the surgical procedure. If affected, such tissues are also removed. A majority of paragangliomas are removed through laparoscopic surgery, which is a minimally invasive procedure. However, large tumors may require traditional open surgery. Following surgery, the levels of catecholamines are checked in the blood or urine. Normal levels indicate complete removal of all the paragangliomas.

• Radiation Therapy: In this procedure, strong beams of energy are focused on destroying the cancer cells or preventing them from recurring while saving as much of the surrounding healthy tissue as possible. There are two types of radiation therapy which include, external and internal radiation therapy. The type of radiation therapy that will be preferred depends on whether the cancer is localized, regional, metastatic, or recurrent. Malignant paragangliomas are treated with external radiation therapy or 131l-MIBG therapy.

• Chemotherapy: Chemotherapy is the most preferred therapy for treating metastatic paragangliomas. This treatment involves using drugs that cease the development of cancer cells by killing them or preventing them from proliferating. The drugs are given intravenously (through a vein). Though chemotherapy is effective, it has a few side effects.

• Ablation Therapy: It is a minimally invasive procedure in which very high or very low temperatures are used to destroy the tumors. Ablation therapies include:

1. Radiofrequency Ablation: This therapy employs the use of radio waves to heat and destroy cancer and abnormal cells.

2. Cryoablation: This therapy employs the use of liquid nitrogen or liquid carbon dioxide that is used to freeze and destroy cancer and abnormal cells.

• Targeted Therapy: This therapy uses medications or other substances to target and attack specific cancer cells without damaging the healthy cells. Targeted therapies are beneficial in treating metastatic and recurrent paragangliomas. Currently, researches are in progress to study the efficacy of a type of targeted therapy called tyrosine kinase inhibitor therapy which employs the use of a tyrosine kinase inhibitor called Sunitinib in treating metastatic paraganglioma.

Conclusion:

A paraganglioma is a non-cancerous growth that develops from a specific type of nerve cell that is present throughout the body. It is a very uncommon (rare) condition. The occurrence of paraganglioma cannot be prevented. Individuals with a small paraganglioma that has not metastasized (spread) have a five-year survival rate of about 95 %, while those with large paragangliomas or those experiencing recurrence have a five-year survival rate between 34 % and 60 %. Benign or malignant untreated paragangliomas can result in serious, life-threatening complications due to the excess secretion of adrenaline and noradrenaline.