Pheochromocytoma - Adrenal gland -

This article will help you read and understand your pathology report for pheochromocytoma.

by Ashley Flaman MD and Bibianna Purgina MD FRCPC, reviewed on May 4, 2020

Pheochromocytoma

Quick facts:

  • A pheochromocytoma is a type of neuroendocrine tumour.
  • It starts in the medulla of the adrenal gland.
  • Hormones produced by the tumour cells can cause symptoms such as a racing heart, headaches, sweating, and high blood pressure.
  • Most (about 75-90%) of pheochromocytomas are non-cancerous tumours.

The normal adrenal glands

The adrenal glands are small organs that sit just on top of your kidneys at the back of your abdomen. The adrenal glands are responsible for producing hormones (chemical signals released into the bloodstream) to help regulate functions in the rest of the body.

The adrenal glands are made up of two parts, an outer cortex and an inner medulla. The cells in the outer cortex are called adrenal cortical cells and they produce hormones to help control things like the amount of water and salt in the body and the body’s response to stress.

The cells in the inner medulla are called neuroendocrine cells and they produce hormones to control the body’s sympathetic (“fight or flight”) response. The hormones made by these cells include epinephrine (adrenaline) and norepinephrine (noraderenaline). When these hormones are released into the blood they cause your heart rate and blood pressure to increase.

What is a pheochromocytoma?

A pheochromocytoma is a type of neuroendocrine tumour. It starts from the specialized neuroendocrine cells in the medulla of the adrenal gland. 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.

Most (about 75-90%) of pheochromocytomas are non-cancerous (benign) 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 pheochromocytoma, you will be asked to follow up regularly with your doctor to ensure the tumour has not spread.

A paraganglioma is a very similar type of tumour that is also made up of neuroendocrine cells. Most paragangliomas start in the head, neck, or in the back along the spine.

How do pathologists make this diagnosis?

When examined under the microscope, a pheochromocytoma is made up of cells that look similar to one and other. The tumour is typically surrounded by a thin layer of tissue called a capsule. The tumour cells are usually arranged in round groups that pathologists describe as “zellballen architecture”, 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. Pheochromocytoma cells are positive for neuroendocrine markers such as synaptophysin and chromogranin. The sustentacular cells are positive for a protein called S-100.

Genetic syndromes associated with pheochromocytoma

Some people inherit a genetic change which 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).

Pheochromocytoma of the Adrenal gland Scaled Score (PASS)

The PASS score is a tool that doctors use to predict the behavior 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 a cancer and spread to other parts of the body.

In order to determine the PASS score, your pathologist will look for specific microscopic features (listed in the table below). Each feature is given a set number of points and which are added up to give the total PASS score.

Microscopic feature What it means

Points for this feature

Invasion of periadrenal adipose tissue The tumour cells have spread outside the adrenal gland and into the fat that surrounds it.

2

> 3 mitoses for every 10 high power fields There are more than 3 dividing cells in a pathologist’s 10 fields of view at 400X magnification (high power fields).

2

Atypical mitoses The dividing cells look abnormal when examined under the microscope. This leads to new cells which are unable to function normally.

2

Necrosis The tumour cells are dying.

2

Cellular spindling The tumour cells are longer than they are round.

2

Cellular monotony All of the cells look exactly the same as each other.

2

Large nests or diffuse growth The cells are growing in large groups instead of forming small cell balls (zellballen).

2

High cellularity There are more tumour cells and they are more closely packed together than normally expected for a pheochromocytoma.

2

Marked nuclear pleomorphism All of the cells look very different from each other.

1

Capsular invasion The tumour cells are spreading past the tumour capsule into the tissue outside of the adrenal gland.

1

Vascular invasion The tumour cells have entered blood vessels.

1

Hyperchromasia The part of the cell that holds the genetic material, the nucleus, is much darker than normal.

1

Other helpful resources

NET patient foundation

National Institutes of Cancer

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