Adrenocortical carcinoma

by Jason Wasserman MD PhD FRCPC
March 6, 2023

Adrenocortical carcinoma is a type of adrenal gland cancer. The tumour starts from the cells normally found in the cortex (outer layer) of the adrenal gland. Although adrenocortical carcinoma is a rare tumour it is the most common type of adrenal gland cancer.

What are the symptoms of adrenocortical carcinoma?

The symptoms of adrenocortical carcinoma depend on the types of hormones produced by the tumour cells. Tumours that produce sex hormones such as androgens can cause women to develop secondary male characteristics. Tumours that produce cortisol are associated with swelling of the face and abdomen, muscle weakness, high blood pressure, and increased blood sugar levels. Some tumours do not cause any symptoms and the tumour is found incidentally when imaging tests are performed for other reasons.

How is this diagnosis made?

A combination of abdominal imaging (MRI or CT scan), blood tests, and pathologic analysis is required to make the diagnosis of adrenocortical carcinoma. After the tumour is identified, blood tests are performed to determine if the tumour is producing any hormones. Most patients are then offered surgery to remove the tumour. For some patients, a surgical procedure called a biopsy may be performed before the tumour is removed completely.

Microscopic features of the tumour

When examined under the microscope the tumour is made up of abnormal-looking adrenocortical cells. The cells are usually large and the cytoplasm (body of the cell) may appear clear or eosinophilic (pink). Mitotic figures (tumour cells dividing to create new tumour cells) are commonly seen. In addition, areas of necrosis (dead or dying tumour cells) are also commonly seen.

The tumour may be surrounded by a thin layer of tissue called a tumour capsule and this capsule may separate the tumour from any remaining normal adrenal gland. Adrenocortical carcinoma is an invasive tumour which means that it spreads into normal tissue. Invasion through the tumour capsule is called capsular invasion. Other types of invasion that are commonly seen include vascular invasion and lymphatic invasion. These types of invasion are described in more detail in the sections below.

Adrenocortical carcinoma
Adrenocortical carcinoma. This picture shows a tumour made up primarily of eosinophilic (pink) cells.

Tumour capsule invasion

Most adrenocortical carcinomas are surrounded by a thin layer of tissue called a tumour capsule. Tumour capsule invasion means that the cancer cells have broken through the tumour capsule and have spread into the surrounding normal adrenal gland or tissue outside of the adrenal gland.

tumour capsule invasion

Vascular invasion

Vascular invasion means that cancer cells were found in a blood vessel, typically a vein, outside of the tumour. When found in association with an adrenocortical carcinoma, vascular invasion is very important for two reasons. First, it supports the diagnosis and helps differentiate this tumour from the similar-looking but non-cancerous adrenal cortical adenoma. Second, it is associated with a worse prognosis as vascular invasion allows cancer cells to spread to distant parts of the body such as the lungs.

Lymphatic invasion

Lymphatic invasion means that cancer cells were found inside a lymphatic vessel. Lymphatic vessels are very small channels that allow waste, extra fluid, and cells to drain out of a tissue. Lymphatic invasion is important because it is associated with an increased risk that cancer cells will spread to lymph nodes.

Ki-67 labelling index

Ki-67 is a protein that is found in cells that are in the process of dividing to create new cells. Pathologists use a test called immunohistochemistry to see cells that are making Ki-67. The Ki-67 labelling index is the number of cancer cells making Ki-67 divided by the total number of cancer cells. The index is typically presented as a percentage. For example, a Ki-67 labelling index of 25% means that 25% of the cancer cells in one area of the tumour were making Ki-67 and in the process of dividing to create new cancer cells. The Ki-67 labelling index is very important because adrenocortical carcinomas typically have an index over 5% while the labelling index in the similar but non-cancerous adrenal cortical adenoma is typically less than 5%. The Ki-67 labelling index also helps doctors decide when to offer medications such as mitotane.

Ki-67 labeling index

Weiss score

The Weiss score is a system developed to help pathologists determine if an adrenal tumour is a cancerous tumour such as adrenocortical carcinoma or a non-cancerous type of tumour called adrenal cortical adenoma. The Weiss score includes 9 features that pathologists look for when they are examining the tumour under the microscope. Each microscopic feature is given 1 point. A total score of 3 or more suggests that the tumour is likely to behave like cancer and should be called adrenocortical carcinoma. In contrast, a total score of less than 3 or more suggests that the tumour is more likely to behave in a non-cancerous manner and should be called adrenal cortical adenoma.

Here are the 9 features used to determine the Weiss score:

  • High nuclear grade.
  • More than mitotic figures (dividing tumour cells) 5 per 10mm2.
  • Atypical mitotic figures.
  • Necrosis (tumour cell death).
  • Diffuse architecture (tumour cells growing in large groups).
  • Clear cells make up less than 25% of the tumour.
  • Tumour capsule invasion.
  • Vascular invasion.
  • Lymphatic invasion.
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