This article will help you read and understand your pathology report for gastrointestinal stromal tumour.
by Ipshita Kak MD FRCPC, reviewed on October 14, 2020
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 called mucosa, muscular wall, and outer surface called serosa.
The muscular wall contains specialized cells called 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.
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.
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.
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.
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. Continue reading to learn more about the information found in this report.
Grade is a word pathologists use to describe how different the 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. Using this measurement, low grade tumours have no more than 5 mitotic figures while high grade tumours have more than 5 mitotic figures.
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.
Immunohistochemistry allows your pathologist to distinguish GIST from other tumours that may look similar to it under the microscope.
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.
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 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.
The spread of tumour cells from the tumour to another part of the body is called a metastasis. The risk of metastasis from a GIST 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.
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 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. A negative margin means that no tumour cells were seen at any of the cut edges of tissue.
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.
GISTs are given a tumour stage between 1 and 4 based solely on the size of the tumour.
GISTs are given a nodal stage of 0 or 1 based on the absence or presence of tumour cells in a lymph node.
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.
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.
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).