What is Gastrointestinal Stromal Cancer?
Gastrointestinal stromal tumors (GISTs) are the most common tumors found in the supportive tissue of the digestive system, making up 80% of all such tumors and around 0.1 to 3% of all types of cancer in the digestive system. About 30% of these tumors are cancerous. These tumors can be found anywhere within the digestive system, but they are most often found in the stomach (60%) or small intestine (20% to 30%). They can also occasionally be found outside of the digestive system, most commonly in the fatty tissue that covers the stomach and intestines (the omentum), the folds of tissue that connect the intestines to the abdominal wall (the mesentery), or behind the abdominal cavity (retroperitoneum).
GISTs were first recognized in the 1980s, when they were thought to be tumors of smooth muscle (the type of muscle found in the walls of organs like the stomach and intestines). However, advances in laboratory techniques (such as immunohistochemistry, which uses antibodies to visualize specific proteins in a tissue sample) and the discovery of certain types of genetic changes in these tumors in the last 20 years have led to the understanding that GISTs are a distinct type of tumor.
What Causes Gastrointestinal Stromal Cancer?
Gastrointestinal stromal tumors, or GISTs, are related to a special type of cell found in the body called interstitial cells of Cajal. However, it is not certain whether GISTs originate directly from these cells or from cells that eventually become them. A majority of GISTs are caused by certain mutations (changes in the DNA) that affect proteins known as KIT or PDGFRA.
These mutations cause the proteins involved to be constantly active, leading to an abnormal growth of cells (hyperplasia) and eventually resulting in the formation of a tumor (neoplasia). While these mutations are the cause for most cases of GISTs, they can also be inherited, causing rare familial GISTs.
GISTs that occur without any changes in the KIT or PDGFRA proteins are often referred to as “wild-type” GISTs. These GISTs can be caused by a variety of other mutations including NF1, BRAF, and HRAS. They are sometimes seen in conjunction with certain disease syndromes like neurofibromatosis type 1, the Carney triad (combination of GIST, paraganglioma, and pulmonary chondroma), and the Carney-Stratakis syndrome (combination of GIST and paraganglioma).
Risk Factors and Frequency for Gastrointestinal Stromal Cancer
GISTs, or gastrointestinal stromal tumors, can arise at any stage of a person’s life, but they’re predominantly found in people who are in their 60s. The rates at which GISTs are being diagnosed varies in different regions. In Europe and the United States, for example, about 6.5 to 14.5 yearly cases of GISTs are reported for every 100,000 people. When taking age into consideration, about 0.68 to 0.8 out of every 10,000 diagnose with GIST. Unfortunately, we don’t have accurate global figures for GISTs because past population studies have been too similar. Men and women are both equally likely to develop GIST.
- GISTs can occur at any age, but are usually diagnosed in people in their 60s.
- In Europe and the US, yearly diagnosis rates are between 6.5 to 14.5 per 100,000 people.
- When age is taken into account, 0.68 to 0.8 per 10,000 people are diagnosed with GIST.
- Global statistics on GIST occurrence are not available due to similarities in past population studies.
- GISTs affect both males and females nearly equally.
Signs and Symptoms of Gastrointestinal Stromal Cancer
Gastrointestinal stromal tumors, also known as GISTs, can cause a range of symptoms. The most common sign of these tumors is gastrointestinal bleeding. This bleeding could be acute, appearing as dark, tarry stools (melena) or bright red or maroon stools (hematochezia). The bleeding could also be chronic, leading to anemia and its associated symptoms. Additionally, GISTs can cause symptoms related to a mass effect, where the tumor causes problems due to its size or location. These symptoms could include abdominal pain, feeling full early during meals, a bloated stomach, or a lump that can be felt in the abdomen. However, in some cases, GISTs are discovered incidentally during surgery, medical imaging, or autopsy.
- Dark, tarry stools (melena)
- Bright red or maroon stools (hematochezia)
- Anemia and its associated symptoms
- Abdominal pain
- Feeling full early during meals
- A bloated stomach
- A lump that can be felt in the abdomen
Testing for Gastrointestinal Stromal Cancer
If you’re experiencing symptoms or if a doctor suspects you may have a type of tumor called a gastrointestinal stromal tumor (GIST), your examination will start with a routine health history check and a physical examination. If you have a noticeable mass in your abdomen, a CT scan, which makes use of special dyes and X-rays to create detailed images, is usually the best way to assess it.
In a CT scan, GISTs show up as fillable, solid lumps that have smooth edges. If you need to avoid radiation or you’re allergic to the dye used in a CT scan, an MRI, which uses a combination of radio waves and a strong magnetic field to create images of your internal organs, could be used instead.
If you’re experiencing bleeding in your digestive tract, endoscopy is usually the best evaluation. It involves using a thin tube with a light and camera to view your digestive tract. GISTs are often similar to other sub-surface lumps usually having a smooth bulge covered with normal-looking lining of the digestive tract.
Tumor-specific ultrasound used during endoscopy can help doctors tell the difference between GISTs and other lumps. In this scan, a GIST appears as a hollow solid lump coming from the second or fourth layers of the digestive tract wall.
The only certain way to diagnose a GIST is to examine the tumor’s tissue, looking at both its structure and its protein makeup. If the specimen looks like a GIST under the microscope, tests should then be done to confirm a protein called KIT is present. If the tumor looks like a GIST but doesn’t test positive for KIT, other tests can be done to confirm the diagnosis.
The tissue sample for these tests can be taken through biopsy or after surgical removal. If the tumor appears easy to remove and doesn’t require therapy before surgery, biopsy may not be needed before removing the tumor. This can reduce the risk of tumor spreading or bleeding during biopsy.
If a biopsy is necessary to diagnose a GIST or decide the best treatment method, a specialist will perform a fine-needle aspiration (FNA) during an ultrasound scan. This involves using a thin needle to collect a sample of your tumor for testing.
A gene mutation test should be done for all GISTs, as some genes can make the tumor resistant to standard therapy. It’s also recommended to get a CT scan or MRI to look for any signs of spread and determine if the tumor can be removed with surgery.
Treatment Options for Gastrointestinal Stromal Cancer
The treatment of gastrointestinal stromal tumors, which are a type of cancer in the digestive tract, will largely depend on how advanced the disease is. The management of these tumors that are smaller than 2 centimeters is a topic under discussion but given the reduced risk they pose, it could be possible to observe them using an endoscopic ultrasound, a procedure using a small camera and a device to produce sound waves for creating images of the inside of your body.
For tumors larger than 2 centimeters that are localized (limited to a certain area), surgical removal remains the main method of treatment. In patients where the disease has progressed to a stage where it’s not possible to remove the entire tumor surgically without causing extreme damage or loss of function to the body, a drug named imatinib can be used before the surgery. This helps in reducing the size of the tumor. For high-risk diseases, it is suggested that additional therapy (adjuvant therapy) be given after the surgery with a class of drugs called tyrosine kinase inhibitors, primarily imatinib.
In cases where the disease cannot be removed surgically or has spread to other parts of the body (metastatic disease), it is recommended to treat patients with tyrosine kinase inhibitors. Imatinib is the first choice for this treatment. In patients where imatinib is not working, the dose can be increased or another drug, sunitinib, can be administered as the second line of treatment. Regorafenib is the third line of treatment. The doctor will usually monitor the response to the treatment using a CT scan, which is a type of X-ray that can provide detailed pictures of the inside of the body.
What else can Gastrointestinal Stromal Cancer be?
When diagnosing gastrointestinal stromal tumors (GISTs), doctors take into account the patient’s symptoms and any previous medical information. This condition can cause different symptoms, and therefore, many diseases can mimic it. If a patient is showing signs of gastrointestinal bleeding or anemia, the doctor might need to rule out the following conditions:
- Other cancers in the digestive tract,
- Diverticular bleeding,
- Blood vessel lesions,
- Inflammatory bowel disease,
- Peptic ulcer disease,
- Gastritis, or
- Esophagitis.
If the patient’s symptoms align with an advanced tumor mass, other internal abdominal cancers may need to be ruled out. In cases where the patient has subepithelial mass lesions observed during an endoscopy, the doctor may consider:
- Leiomyomas,
- Leiomyosarcomas,
- Schwannomas,
- Lipomas, and
- Melanomas.
Finally, here are some possibilities the doctor might need to consider while diagnosing GISTs in general:
- Epithelioid hemangioendothelioma,
- Fibromatosis,
- Metastatic melanoma,
- Lymphoma,
- Schwannoma,
- Leiomyoma,
- Benign tumors of the small intestine,
- Dermatofibroma,
- Stomach cancer,
- Leiomyosarcoma,
- Lipomas,
- Solitary fibrous tumor,
- Inflammatory bowel disease,
- Diverticulosis,
- Gastritis, and
- Peptic ulcer disease.
In conclusion, diagnosing GISTs is a comprehensive process, and doctors would have to consider a range of conditions based on the patient’s symptoms to reach the correct conclusion.
Surgical Treatment of Gastrointestinal Stromal Cancer
Gastrointestinal stromal tumors (GISTs) that are bigger than 2 cm and easy to remove are typically treated with surgery. The aim of the surgery is to completely remove the tumor, being careful to take out all of it without bursting the tumor’s outer layer, known as the pseudocapsule.
If the GISTs are less than 5 cm in size, the tumor can be removed through a minimal invasive surgery, also known as laparoscopic surgery. It’s a safe and efficient procedure. However, if the GISTs are larger, traditional or open surgery is preferred. This is done to reduce the chance of accidentally rupturing the pseudocapsule, which could scatter tumor cells into the abdomen and increase the risk of the tumor coming back.
When these tumors are removed, it’s not necessary to also remove the lymph nodes, because these tumors rarely spread to these areas. The main risks for this type of surgery are the rupture of the pseudocapsule and bleeding.
If the disease has spread to surrounding areas (locally advanced disease), there’s a medication called imatinib that might be used before surgery. This medication aims to shrink the tumors, making them easier to remove. More details about this will be discussed in the section about medical oncology.
What to expect with Gastrointestinal Stromal Cancer
The outlook for patients with gastrointestinal stromal tumors, or GISTs (a type of tumor that usually begins in cells in the wall of the gastrointestinal tract), is determined by several factors. The main elements include the original location of the tumor, the number of cells in the tumor that are dividing and growing (known as the “mitotic count”), and the overall size of the tumor.
Other factors that can affect the prognosis of GISTs are negative margins, which means no trace of cancer can be found in the tissue surrounding the tumor, and whether or not the tumor ruptures, or breaks open, during removal surgery. Rupture can lead to the spread of cancer cells.
Medical groups have created several scoring systems to predict how well a patient may do after diagnosis. These include systems developed by the National Institutes of Health (NIH) and the Armed Forces Institute of Pathology (AFIP). There is also a prediction tool known as a “prognostic nomogram” developed at Memorial Sloan Kettering Cancer Center. This tool, created using information from past cases, has been shown to be more accurate than NIH models and as accurate as the AFIP model.
Possible Complications When Diagnosed with Gastrointestinal Stromal Cancer
The most frequent complications of gastrointestinal stromal tumors involve bleeding in the digestive tract or the large size of the tumors. These tumors could cause sudden bleeding in the digestive tract, indicating as dark stool or vomiting blood, or cause steady digestive bleeding that leads to iron-deficiency anemia. Additionally, these tumors often cause blockages in the intestines, internal abdominal bleeding, and rupture that can result in an inflammation of the membrane lining the abdominal wall.
Common Complications:
- Bleeding in the digestive tract
- Digestive tract bleeding leading to Iron-deficiency anemia
- Blockages in the intestines
- Internal abdominal bleeding
- Rupture leading to inflammation of the membrane lining the abdominal wall
Preventing Gastrointestinal Stromal Cancer
Gastrointestinal stromal tumors, or GISTs, are a rare type of tumor that can occur anywhere along your digestive tract – from your esophagus down to your rectum. But they are most found in the stomach or small intestine. They usually happen later in life, with the average age of diagnosis being in the 60s, but can happen at any age. In children, these tumors are often due to rare inheritable genetic conditions.
Common signs of GISTs include bleeding in the digestive tract, as well as stomach pain and a feeling of fullness. Bleeding in the digestive tract can show up as blood in your poop, extremely dark poop, or vomiting blood. Depending on the size and location of the tumor, doctors may be able to spot it using a CT scan, MRI, or an endoscopy, which is when a camera is used to look inside your body.
Diagnosis of GISTs involves taking a tissue sample (biopsy) and examining it under a microscope. The doctors look for certain patterns of cell arrangement and genetic mutations. If they see these, it could confirm a diagnosis of GIST.
If possible, the preferred treatment for GISTs is surgery, but sometimes the tumor has spread too much or is too difficult to remove. In these situations, medication known as tyrosine kinase inhibitors can be used to shrink the tumor to make it easier to remove. These drugs can again be used after surgery, for high-risk cases, typically for 3 years.
In some cases, where surgery is not possible, these medications can be taken indefinitely to help control the growth of the tumor.
