This article will help you read and understand your pathology report for paraganglioma.
by Ashley Flaman MD and Bibianna Purgina MD FRCPC, updated December 31, 2020
Your body is controlled by your brain. The brain uses long wires called nerves to send and receive information from the body. The brain, spinal cord, and nerves make up the nervous system.
The nervous system is divided into two parts: the somatic system and the autonomic system. The somatic system is responsible for the parts of your body that you can control, like the movement of your arms and legs. The autonomic system is responsible for the parts of your body that you cannot control, like your heart rate and the dilation of your pupils.
The autonomic nervous system is also divided into two parts: the sympathetic system and the parasympathetic system. Your body is constantly shifting balance between the sympathetic (“fight or flight”) state and the parasympathetic (“rest and digest”) state. These two systems are controlled by small collections of specialized nerve tissue called paraganglia. Paraganglia are found throughout the body although most are found in the head, neck, and abdomen near the spine.
Paraganglia are made up of specialized cells called neuroendocrine cells. These cells produce hormones that change the way your other organs behave in response to either sympathetic or parasympathetic signals from the brain. The hormones made by these cells include epinephrine and acetylcholine.
A paraganglioma is a type of neuroendocrine tumour. It starts from the specialized neuroendocrine cells in the paraganglia. Hormones produced by the tumour cells can cause symptoms such as a racing heart, headaches, sweating, and high blood pressure. However, many paragangliomas do not cause any symptoms and are found when imaging such as a CT scan or MRI is performed for an unrelated reason or because the tumour is in a location that can be seen or felt.
Most (about 65-90%) of paragangliomas are non-cancerous tumours. However, some may behave more like a cancer by spreading to other parts of the body. Unfortunately, there are no findings that pathologists can see under the microscope that can definitely separate non-cancerous from cancerous tumours with 100% certainty. Therefore, if you are diagnosed with a paraganglioma, you will be asked to follow up regularly with your doctor to ensure the tumour has not spread.
When examined under the microscope, a paraganglioma is made up of cells that look similar to one and other. The tumour is often surrounded by a thin layer of tissue called a capsule. The tumour cells are usually arranged in round groups that pathologists describe as “zellballen”, which translates from German to mean “cell balls”. The groups of cells are surrounded by specialized cells called sustentacular cells which support the neuroendocrine cells.
Your pathologist may perform a test called immunohistochemistry to confirm the diagnosis. Paraganglioma cells are positive for neuroendocrine markers such as synaptophysin and chromogranin. The sustentacular cells are positive for a protein called S-100.
Some people inherit a genetic change which makes them more likely to develop a paraganglioma. This change is associated with a condition called hereditary (or familial) paraganglioma-pheochromocytoma syndrome.
Your pathologist may test for hereditary paraganglioma-pheochromocytoma syndrome by performing an immunohistochemical test for SDHB. Tumour cells that produce SDHB will be described as positive or reactive. Tumour cells that do not produce SDHB will be described as negative or non-reactive.
If this test shows that the tumour cells are negative for SDHB, your pathologist may recommend further genetic testing. Other genetic syndromes associated with paragangliomas and pheochromocytomas include Von Hippel-Lindau, multiple endocrine neoplasia type 2 (MEN2A and MEN2B), and neurofibromatosis 1 (NF1).