Gastrointestinal tract -

Gastrointestinal stromal tumour (GIST)

This article was last reviewed and updated on December 30, 2018
by Ipshita Kak MD FRCPC

Quick facts:

  • Gastrointestinal stromal tumour (GIST) is a type of cancer called a sarcoma.

  • It can develop anywhere in the gastrointestinal tract but the most common location is the stomach.

 

The normal gastrointestinal tract

The gastrointestinal tract starts at the mouth and ends at the rectum. It functions to transport, digest, and absorb food so that it can be used as energy for your body. The gastrointestinal tract is composed of an inner surface (mucosa), muscular wall, and outer surface (serosa).

 

The muscular wall contains specialized cells (interstitial cells of Cajal) that 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 is a gastrointestinal stromal tumour (GIST)?

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

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. A biopsy can be helpful in diagnosis; however, these tumours are usually too deep in the muscle to be sampled in a biopsy done on endoscopy.

Histologic grade

Grade is a word pathologists use to describe how different tumour cells look or behavior compared to normal cells in that same location of the body.

 

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.

 

Mitosis is the cellular process by which cells divide and dividing cells have a unique look that helps pathologists recognize them. Cells that are in the process of dividing are called mitotic figures.

 

Your pathologist will determine the grade of your tumour by counting the number of mitotic figures in a microscopic area measuring 5 millimeters by 5 millimeters.

 

Why is this important? Using this measurement, low grade GISTs have no more than 5 mitotic figures while high grade GISTs have more than 5 mitotic figures.

Tumour size

Your pathologist will measure the tumour after it has been removed from your body and the largest dimension is typically included in the report. For example, if the tumour measures 5.0 cm by 3.2 cm by 1.1 cm, the report may describe the tumour size as 5.0 cm in greatest dimension.

Tumour location

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.

 

Occasionally, GISTs can also develop outside the gastrointestinal tract in the mesentery, omentum, retroperitoneum, and pelvis.

Most GISTs start in the muscular wall of the gastrointestinal tract although they can grow towards the inner surface (mucosa) or outer surface (serosa) of the organ. Tumours that extend into the mucosa behave worse than those that are limited to the muscular wall.

Risk assessment score

The risk that tumour cells will travel to another part of the body (distant metastasis) is determined by a risk assessment score that includes the number of mitotic figures, the location of the tumour in the gastrointestinal tract, and the 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.

Metastasis

Metastatic disease describes the process where tumour cells escape the main tumour and travel to another part of the body. The most common sites that GISTs spread to are liver and the tissues that line the inside of the abdominal organs (peritoneum). The lungs are also very rare site of spread.

Tumour cells only rarely travel to lymph nodes and for this reason lymph nodes are rarely removed in most GIST surgeries.

Margins

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. For GIST, a margin is considered ‘positive’ when there are tumour cells at the very edge of the cut tissue.

 

Why is this important? A positive margin is associated with a higher risk that the tumour will come back in the same site after treatment (local recurrence).

Pathologic stage (pTNM)

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.

 

Pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.

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 between 0 and 1 based on the absence or presence of tumour cells in a lymph node.
 
If no lymph nodes are involved the nodal stage is 0. If no lymph nodes are submitted for pathological examination, which is a common occurrence in GISTs, the nodal stage is not applicable.

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.

Molecular tests
​Each cell in your body contains a set of instructions that tell the cell how to behave. These instructions are written in a language called DNA and the instructions are stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes and each gene tells the cell how to produce piece of the machine called a protein.

 

If the DNA becomes damaged or if it cannot be read accurately, the cell will be unable to produce the proteins it requires to function normally. An area of damaged DNA is called a mutation and mutations are one of the most common causes of cancer in humans.

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.

 

Why is this important? 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).

Immunohistochemistry

Immunohistochemistry (IHC) is a commonly used test that allows pathologists to better understand cells based on the specific proteins they produce. This test allows pathologists to better understand both the function and origin of the cell. By performing immunohistochemistry, your pathologist can ‘see’ these proteins inside the cell.

The two most common immunohistochemical markers use 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.

Why is this important? Immunohistochemistry allows your pathologist to distinguish GIST from other tumours that may look similar to it under the microscope.

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