Gastrointestinal stromal tumours (GISTs)

Where GISTs develop

Signs and symptoms

Diagnosis

Types of GISTs

Grading

Staging

Disease progression

Treatment

 

Gastrointestinal stromal tumours (GISTs), or GI stromal tumours, often start in the walls of the gastrointestinal  (GI) tract. The cells of these tumours are similar to the interstitial cells of Cajal (ICCs). ICCs are part of the nervous system and receive signals from the brain. Based on these signals, ICCs make muscles in the stomach, small intestine and large intestine tighten (contract) and relax (expand) to help move food and liquid through the digestive system (a process called peristalsis).

 

GISTs are a type of soft tissue sarcoma. They are different from the more common types of GI tract cancers, which are carcinomas.

 

GISTs most often occur in people over 50, although they may develop at any age. The exact cause of GISTs is not known. Most GI stromal tumours have a mutation in the KIT (or c-KIT) gene. This mutation causes the body to produce too much of the KIT protein. A mutation in a different gene causes the body to produce too much platelet derived growth factor receptor alpha (PDGFRA). Both the KIT and PDGFRA proteins are enzymes called tyrosine kinases, which signal cells to grow and can trigger some GISTs to grow in an uncontrolled way.

Where GISTs develop

A GIST can occur anywhere in the GI tract, but they most often develop in the stomach. The small intestine is the second most common location. GISTs can also develop in the esophagus, colon, rectum, omentum and mesentery (a membrane that covers abdominal organs and attaches the bowel to the abdominal wall).

 

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Signs and symptoms

The signs and symptoms of GISTs depend on if they develop in the stomach or small intestine. Signs and symptoms may include:

  • nausea
  • vomiting
  • loss of appetite
  • weight loss
  • a lump in the abdomen
  • abdominal pain or discomfort
  • bleeding from the GI tract, such as vomiting blood or blood in the stool

 

Early stage GISTs usually do not cause symptoms. Symptoms tend to occur only when the tumour has grown large enough to cause problems.

 

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Diagnosis

If the signs and symptoms of a GIST are present, or if the doctor suspects a GIST, tests will be done to make a diagnosis. Tests will depend on where the GIST is located, but may include:

  • physical examination
  • laboratory tests
    • complete blood count
    • blood chemistry tests
  • imaging
    • upper GI series (barium swallow)
    • small bowel enema or barium enema (lower GI series)
    • CT scan or MRI of the abdomen and pelvis
    • ultrasound of the abdomen
    • PET scan – may be done in certain situations
  • endoscopy
    • gastroscopy or upper GI endoscopy
  • biopsy
    • may be done during an endoscopy procedure

 

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Types of GISTs

GISTs may be benign or malignant.

  • Benign tumours are non cancerous growths that do not spread (metastasize) to other parts of the body. They are not usually life threatening.
    • Smaller tumours that are less than 5 cm (2 inches) in diameter are usually non-cancerous.
    • Some low grade benign GISTs can spread within the abdomen or to the liver.
  • Malignant tumours are cancerous growths that have the potential to spread (metastasize) to other parts of the body.
    • Larger GISTs, usually larger than 5 cm, are more likely to be malignant. Smaller tumours have a better prognosis than larger tumours.
    • GISTs that develop in the small intestine are often larger and more aggressive than those that develop in the stomach.

 

GISTs are different from leiomyomas, leiomyosarcomas and schwannomas. Even though GIST cells look like muscle or nerve cells under a microscope, it is now believed that they do not start in true muscle or nerve cells.

 

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Grading

Grading is a way of classifying GIST cells based on their appearance and behaviour when viewed under a microscope. To find out the grade of a tumour, the biopsy sample is examined under a microscope. A grade is given based on how the cancer cells look and behave compared with normal cells (differentiation). This can give the healthcare team an idea of how quickly the cancer may be growing and how likely it is to spread.

 

The grade of GISTs is based on their mitotic rate, which is how fast the cancer cells are growing and dividing. The grade is described as being either low or high. GISTs with a low mitotic rate have a better outcome.

 

Grade

Mitotic rate

Number of mitoses per 50 high power fields (hpf)

low

low

5

high

more than 5

 

Grading plays an important part in planning treatment for GISTs. It can also be used to help estimate the prognosis (future outcome).

 

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Staging

Staging is a way of describing or classifying a cancer based on the extent of cancer in the body. Until recently, there was no standard staging system for GISTs. Now the most common staging system for GISTs is the TNM system. The International Union Against Cancer (UICC) uses the TNM system to describe the extent of many solid tumour cancers.

 

TNM

TNM stands for tumour, nodes, metastasis. TNM staging describes:

  • the size of the primary tumour
  • the number and location of any regional lymph nodes that have cancer cells in them
  • whether the cancer has spread or metastasized to another part of the body

 

Primary tumour (T)

TX

Primary tumour cannot be assessed

T0

No evidence of primary tumour

T1

Tumour is 2 cm (0.8 inches) or less in diameter

T2

Tumour is more than 2 cm but not more than 5 cm (2 inches) in diameter

T3

Tumour is more than 5 cm but not more than 10 cm (4 inches) in diameter

T4

Tumour is more than 10 cm in diameter

 

Regional lymph nodes (N)

NX

Regional lymph nodes cannot be assessed

N0

No regional lymph node metastasis

N1

Regional lymph node metastasis

Note: GISTs rarely spread to the lymph nodes. When a GIST does spread, the regional lymph nodes are those closest to the site of the primary tumour.

 

Distant metastasis (M)

M0

No distant metastasis

M1

Distant metastasis

 

Stage grouping for GISTs

The UICC further groups the TNM data into the stages listed in the tables below, based on where the tumour starts.

 

UICC staging- gastric GIST

UICC Stage

TNM

Mitotic rate

Explanation

stage IA

T1, T2

N0

M0

low

The tumour is no bigger than 5 cm in diameter. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is low.

stage IB

T3

N0

M0

low

The tumour is bigger than 5 cm but not bigger than 10 cm. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is low.

stage II

T1, T2

N0

M0

high

The tumour is no bigger than 5 cm in diameter. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is high.

T4

N0

M0

low

The tumour is bigger than 10 cm. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is low.

stage IIIA

T3

N0

M0

high

The tumour is bigger than 5 cm but not bigger than 10 cm. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is high.

stage IIIB

T4

N0

M0

high

The tumour is bigger than 10 cm. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is high.

stage IV

any T

N1

M0

any rate

The tumour is any size. The cancer has spread to nearby lymph nodes. The cancer has not spread to distant sites. The tumour has any mitotic rate.

 

The tumour is any size. The cancer may or may not have spread to nearby lymph nodes. The cancer has spread to distant sites. The tumour has any mitotic rate.

Note: Staging for gastric (stomach) GISTs is also used for GISTs of the omentum.

 

UICC staging – small intestine GIST

UICC stage

TNM

Mitotic rate

Explanation

stage I

T1, T2

N0

M0

low

The tumour is no bigger than 5 cm in diameter. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is low.

stage II

T3

N0

M0

low

The tumour is bigger than 5 cm but not bigger than 10 cm. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is low.

stage IIIA

T1

N0

M0

high

The tumour is 2 cm or less in size. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is high.

T4

N0

M0

low

The tumour is bigger than 10 cm. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is low.

stage

IIIB

T2, T3, T4

N0

M0

high

The tumour is bigger than 2 cm. The cancer has not spread to nearby lymph nodes or distant sites. The mitotic rate is high.

stage IV

any T

N1

M0

any rate

The tumour is any size. The cancer has spread to nearby lymph nodes. The cancer has not spread to distant sites. The tumour has any mitotic rate.

any T

The tumour is any size. The cancer may or may not have spread to nearby lymph nodes. The cancer has spread to distant sites. The tumour has any mitotic rate.

Note: Staging for small intestine GISTs is used for GISTs of the esophagus, colon, rectum and mesentery.

Recurrent GISTs

Recurrent cancer means that the cancer has come back after it has been treated. It may recur in the same location as the original cancer or it may recur in another part of the body (metastatic GIST).

 

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Disease progression

Cancer cells have the potential to spread from the GI tract to other parts of the body where they can grow into new tumours. This process is called metastasis. The tumours are also called metastasis (singular) or metastases (plural). Metastases are also called secondary tumours.

 

Understanding the usual progression of cancer helps the doctor to predict its probable course, plan treatment and anticipate further care.

 

The most common sites where GISTs spread are:

  • within the abdomen, particularly to the liver or peritoneal cavity (the space in the abdomen that contains the stomach, liver and intestines) – most common site of spread
  • lungs
  • bone

 

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Treatment

GISTs behave differently than other types of soft tissue sarcoma and are treated differently. Treatment plans are designed to meet the unique needs of each person with cancer and are based on:

  • stage
  • location (stomach or small intestine)
  • person's overall health

Surgery

Surgery is usually the main treatment for a GIST that hasn't spread. The goal of the surgery is to completely remove all of the cancer. Nearby lymph nodes are usually not removed because GISTs don't often spread to the lymph nodes.

GISTs in the stomach

Surgery is the main treatment for GISTs in the stomach. The entire tumour and a margin of healthy tissue around it are removed. The types of surgery may include wedge resection, gastrectomy (part or all of the stomach is removed) or surgical bypass.

GISTs in the small intestine

Surgery is also the main treatment for GISTs in the small intestine. Different types of surgery may be done depending on where the GIST is in the small intestine. The types of surgery may include bowel resection, pancreatoduodenectomy (Whipple procedure) or a surgical bypass.

 

Single metastases of GISTs elsewhere in the abdomen, including the liver, can sometimes be surgically removed.

Targeted therapy

Standard chemotherapy drugs are not very effective against GISTs, but imatinib (Gleevec) has been shown to be effective. Imatinib is a type of targeted therapy drug that blocks tyrosine kinase, an enzyme that the tumour needs to grow. Because it blocks this enzyme, imatinib is called a tyrosine kinase inhibitor. It is used to treat GISTs that:

  • cannot be removed by surgery
  • have spread to other organs in the body
  • have come back after treatment (have recurred)

 

Imatinib may also be used to try and shrink a tumour so that it can be surgically removed.

 

Imatinib is often continued until the cancer progresses.

 

Sunitinib (Sutent) is another tyrosine kinase inhibitor. It may be used when the cancer does not respond to imatinib or the person can’t tolerate imatinib.

Radiation therapy

External beam radiation therapy may be offered to relieve symptoms of advanced disease, such as pain or bleeding (palliative radiation therapy).

Recurrent GISTs

Treatment options for GISTs that recur after treatment depend on the location and extent of the recurrence. For most recurrences, imatinib will often be used because it offers the best chance of shrinking tumours. If imatinib does not work at first, the doctor may increase the dose or try sunitinib instead. Sometimes a recurrence of a single, well-defined tumour can be completely removed or destroyed.

 

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For more detailed information on specific drugs, go to sources of drug information.

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