by Ashley Flaman MD and Bibianna Purgina MD FRCPC
June 3, 2022
What is pheochromocytoma?
A pheochromocytoma is a type of neuroendocrine tumour that starts from specialized neuroendocrine cells normally found in a part of the adrenal gland called the medulla. Most pheochromocytomas behave as non-cancerous tumours and will not spread to other parts of the body.
What is the difference between a pheochromocytoma and a paraganglioma?
Pheochromocytoma and paraganglioma are both neuroendocrine tumours that look similar when examined under the microscope. However, unlike pheochromocytomas which only start in the adrenal gland, paragangliomas can start in any location where autonomic ganglion cells are normally found. Paragangliomas are commonly found in the head, neck, or in the back along the spine. Pheochromocytoma is considered an “intra-adrenal paraganglioma”.
What are the symptoms of pheochromocytoma?
Hormones produced by the tumour cells can cause symptoms such as a racing heart, headaches, sweating, and high blood pressure. However, some pheochromocytomas do not cause any symptoms and are only found when imaging such as a CT scan or MRI is performed for an unrelated reason.
How is the diagnosis of pheochromocytoma made?
The diagnosis of pheochromocytoma is usually made after the entire adrenal gland is removed in a procedure called an excision or resection. The gland is then sent to a pathologist for examination under the microscope.
What does a pheochromocytoma look like under the microscope?
When examined under the microscope, a pheochromocytoma is made up of cells that look similar to each other. The tumour is typically surrounded by a thin layer of tissue called a tumour 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.
Most (about 75-90%) of pheochromocytomas are non-cancerous tumours. However, some may behave more like 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 pheochromocytoma, you will be asked to follow up regularly with your doctor to ensure the tumour has not spread.
What other tests may be performed to confirm the diagnosis?
Your pathologist may perform a test called immunohistochemistry to confirm the diagnosis. Pheochromocytoma cells are positive for neuroendocrine markers such as synaptophysin and chromogranin. The sustentacular cells are positive for a protein called S100.
What genetic syndromes are associated with pheochromocytoma?
Some people inherit a genetic change that makes them more likely to develop a pheochromocytoma. 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).
What is the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS)?
Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is a tool that doctors use to predict the behaviour of a pheochromocytoma. A score of 3 or less means that the tumour is likely to behave in a non-cancerous manner and is cured by surgery alone. In contrast, a score of 4 or more means the tumour is more likely to behave like cancer and spread to other parts of the body.
In order to determine the PASS score, your pathologist will look for specific microscopic features. Each feature is given a set number of points and which are added up to give the total PASS score.
- Invasion of periadrenal adipose tissue (2 points) – The tumour cells have spread outside the adrenal gland and into the fat that surrounds it.
- > 3 mitoses for every 10 high power fields (2 points) – There are more than 3 dividing cells in a pathologist’s 10 fields of view at 400X magnification (high power fields).
- Atypical mitoses (2 points) – The dividing cells look abnormal when examined under the microscope. This leads to new cells which are unable to function normally.
- Necrosis (2 points) – The tumour cells are dying.
- Cellular spindling(2 points) – The tumour cells are longer than they are round.
- Cellular monotony (2 points) – All of the cells look exactly the same as each other.
- Large nests or diffuse growth (2 points) – The cells are growing in large groups instead of forming small cell balls (zellballen).
- High cellularity (2 points) – There are more tumour cells and they are more closely packed together than normally expected for a pheochromocytoma.
- Marked nuclear pleomorphism (1 point) – All of the cells look very different from each other.
- Capsular invasion (1 point) – The tumour cells have spread past the tumour capsule into the tissue outside of the adrenal gland.
- Vascular invasion (1 point) – The tumour cells are found inside blood vessels.
- Hyperchromatic tumour cells (1 point) – The part of the cell that holds the genetic material, the nucleus, is much darker than normal.
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