Gastrointestinal stromal tumour (GIST)

by Ipshita Kak MD FRCPC
April 14, 2022


What is a gastrointestinal stromal tumour (GIST)?

A gastrointestinal stromal tumour (GIST) is a type of cancer called a sarcoma. It develops from the interstitial cells of Cajal (ICC) that are normally found in the gastrointestinal tract. GIST can start anywhere along the length of the gastrointestinal tract but is most commonly found in the wall of the stomach.

What are the interstitial cells of Cajal?

Interstitial cells of Cajal are specialized cells that are normally found throughout the gastrointestinal tract, from the esophagus to the rectum. These cells receive signals from the nervous system and in turn, cause alternating contraction and relaxation of the muscular wall helping to move food through the gastrointestinal tract.

What are the symptoms of a gastrointestinal stromal tumour?

GISTs usually do not produce any symptoms until they are large enough to be noticed by the patient as an abdominal mass or when they cause pain. The tumour is more commonly found incidentally on imaging and/or endoscopy done for unrelated reasons.

How do pathologists make the diagnosis of gastrointestinal stromal tumour?

The diagnosis is usually made after a small sample of the tumour is removed in a procedure called a biopsy.  Some tumours are too deep in the muscle for a biopsy to be performed. These tumours will need to be removed completely before a diagnosis can be established.

gastrointestinal stromal tumour

A GIST within the wall of the stomach is shown on the left side of this image.

After the tumour has been removed completely, it will be sent to a pathologist who will prepare another pathology report. This report will confirm or revise the original diagnosis (if a biopsy was performed) and provide additional important information such tumour size and margins. Molecular tests may also be performed. This information is used to determine the cancer stage and to decide if additional treatment is required.

What additional tests may be performed to confirm the diagnosis?

Immunohistochemistry

Immunohistochemistry is a test that allows the pathologist can ‘see’ proteins inside a cell. Immunohistochemistry allows your pathologist to distinguish GIST from other tumours that may look similar to it under the microscope.

The two most common immunohistochemical markers used to confirm the diagnosis of GIST are cKIT (CD117) and DOG-1. Cells that produce a protein will be called positive or reactive. Those that do not produce the protein are called negative or non-reactive. Most GISTs (95%) will be positive for one of these markers.

Molecular tests

Most GISTs have a genetic mutation in one of two genes: KIT or PDGFRA (platelet-derived growth factor receptor A). Your pathologist will probably perform tests to determine which type of mutation is present. The results of these tests are important because targeted medications are offered to patients with specific mutations (for example, imatinib is offered to patients with KIT mutations).

How do pathologists grade gastrointestinal stromal tumours?

Pathologists separate GISTs into two grades, low and high, based on the percentage of tumour cells that are in the process of dividing to create new tumour cells. This process is called mitosis and a cell that is in the process of dividing is called a mitotic figure. Your pathologist will determine the grade of the tumour by counting the number of mitotic figures in a microscopic area measuring 5 millimetres by 5 millimetres. Using this measurement, low-grade tumours have no more than 5 mitotic figures while high-grade tumours have more than 5 mitotic figures.

Where in the gastrointestinal tract is the tumour located?

Stomach GISTs make up more than half (approximately 70%) of gastrointestinal tract GISTs and are associated with a more favourable outcome compared to tumours of the same size that start in the small intestine or rectum.

Most GISTs start in the muscular wall of the gastrointestinal tract although they can grow towards the mucosa or serosa of the organ. Tumours that extend into the mucosa are more likely to spread to other parts of the body than those that are only found in the muscular wall.

Occasionally, GISTs can also develop outside the gastrointestinal tract in the mesentery, omentum, retroperitoneum, and pelvis. The location of the tumour is important because it is used in the risk assessment score (see below).

What is the risk assessment score for gastrointestinal stromal tumour?

The risk assessment score is a system designed to predict the risk of metastatic disease (spread of tumour cells to other parts of the body). Pathologists use three criteria to determine the score: mitotic rate (the number of tumour cells dividing to create new tumour cells), the location of the tumour in the gastrointestinal tract, and the tumour size. The three criteria are combined to determine the overall score.

  • Mitotic rate: The risk of distant metastatic disease is higher when the number of mitotic figures is greater than 5 per 5 high-powered fields.
  • Location: Tumours located in the stomach are associated with the lowest risk of metastatic disease. The risk of metastatic disease is higher for tumours located in the small bowel (duodenum, jejunum, ileum) and rectum.
  • Tumour size: According to this score, the chance of distant metastasis increases at the following tumour size intervals: 2 cm, 5 cm and 10 cm. For example, a 5 cm tumour is associated with a higher risk of metastasis than a 2 cm tumour and a 10 cm tumour is associated with a higher risk of metastasis than a 5 cm tumour.

What is a margin?​

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. The types of margins described in your report will depend on the organ involved and the type of surgery performed. Margins will only be described in your report after the entire tumour has been removed.

A negative margin means that no tumour cells were seen at any of the cut edges of tissue. A margin is called positive when there are tumour cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment.

Margin

How do pathologists determine the pathologic stage (pTNM) for gastrointestinal stromal tumour?

The pathologic stage for gastrointestinal stromal tumours (GISTs) is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer (AJCC). This staging system is not used for children or adults who are known to have a genetic syndrome that is associated with GIST.

The AJCC system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. Generally, a higher number means more advanced disease.

Tumour stage (pT)

GISTs are given a tumour stage between 1 and 4 based solely on the size of the tumour.

  • T1 – The tumour is smaller than or equal to 2 cm in maximum dimension.
  • T2 – The tumour measures more than 2 cm but not more than 5 cm.
  • T3 – The tumour measures more than 5 cm but not more than 10 cm.
  • T4 – The tumour is larger than 10 cm in maximum dimension.​
Nodal stage (pN)

GISTs are given a nodal stage of 0 or 1 based on the absence or presence of tumour cells in a lymph node.

  • N0 – No tumour cells were found in any of the lymph nodes examined.
  • N1 – Tumour cells were found in at least one lymph node.
  • NX – No lymph nodes were sent for pathologic examination.
Metastatic stage (pM)

GISTs are given a metastatic stage between 0 and 1 based on the presence of tumour cells at a distant site in the body (for example the liver, peritoneal surfaces etc). The metastatic stage can only be determined if tissue from a distant site is sent for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as X.

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