Gastrointestinal Stromal Tumor

Gastrointestinal Stromal Tumor

A gastrointestinal stromal tumor (GIST) is a rare type of tumor that arises from the cells of the gastrointestinal tract, particularly the wall of the stomach or small intestine. GISTs belong to a broader category of tumors known as soft tissue sarcomas.

GISTs develop from specialized cells called interstitial cells of Cajal (ICCs), which are responsible for regulating the movement of the digestive tract. Most GISTs have a specific mutation in a gene called KIT or PDGFRA, which leads to the uncontrolled growth of these cells.

GISTs can occur in people of any age but are more commonly diagnosed in adults. The exact cause of GISTs is unknown, and they are not typically associated with lifestyle or environmental factors.

Causes

The cause of gastrointestinal stromal tumors (GISTs) is still not understood. However, the majority of GISTs have been found to have specific genetic mutations that contribute to their development. The most common mutations are found in two genes: KIT (CD117) and PDGFRA.

1. KIT Gene Mutations – The KIT gene provides instructions for producing a protein called KIT receptor tyrosine kinase, which is involved in the regulation of cell growth and division. Mutations in the KIT gene can lead to the activation of this protein, causing uncontrolled cell growth and the formation of GISTs.

Gastrointestinal Stromal Tumor

2. PDGFRA Gene Mutations – The PDGFRA gene also encodes a receptor protein called platelet-derived growth factor receptor alpha. Mutations in the PDGFRA gene can result in the abnormal activation of this protein, leading to the development of GISTs.

In the majority of cases, GISTs are sporadic, meaning they occur randomly without any clear underlying cause. However, in some rare instances, GISTs may be associated with certain genetic syndromes, including –

• Neurofibromatosis type 1 (NF1) – People with NF1 have an increased risk of developing GISTs.
• Carney triad – This rare condition is characterized by the presence of GISTs, paraganglioma (a type of tumor that arises from the cells of the nervous system), and pulmonary chondroma (a benign tumor of the lung).
• Carney-Stratakis syndrome – This syndrome is characterized by the presence of GISTs and paragangliomas. It is caused by specific genetic mutations in the SDHB, SDHC, or SDHD genes.

These genetic mutations are associated with GIST development, not all individuals with these mutations will develop GISTs. The interplay of genetic factors and other environmental or molecular influences likely contributes to the development of these tumors.

Overall, more research is needed to fully understand the underlying causes of GISTs and to identify potential risk factors that may increase a person’s susceptibility to developing these tumors.

Symptoms

The symptoms of gastrointestinal stromal tumors (GISTs) can vary depending on the size, location, and aggressiveness of the tumor. Some individuals with GISTs may not experience any symptoms, while others may have noticeable signs. Common symptoms of GISTs include –

1. Abdominal pain or discomfort – This is a common symptom and is often described as a dull ache or a sense of fullness in the abdomen. The pain may be intermittent or persistent.
2. Gastrointestinal bleeding – GISTs can cause bleeding in the digestive tract, which can lead to symptoms such as blood in the stool (which may appear dark or tarry), vomiting blood (hematemesis), or rectal bleeding.
3. Anemia – Chronic bleeding from GISTs can result in iron deficiency anemia, characterized by fatigue, weakness, shortness of breath, pale skin, and dizziness.
4. Nausea and vomiting – GISTs located in the stomach or small intestine can cause feelings of nausea and may lead to vomiting.
5. Early satiety – GISTs may obstruct the normal passage of food through the digestive tract, causing a sensation of fullness even after consuming small amounts of food.
6. Palpable mass – In some cases, a noticeable lump or mass may be felt in the abdomen. This may occur if the tumor has grown to a significant size.
7. Weight loss – Unintentional weight loss may occur due to a decreased appetite, early satiety, and the body’s increased metabolic demands associated with cancer.

These symptoms can also be caused by various other conditions, and their presence does not necessarily indicate the presence of a GIST. If you experience persistent or concerning gastrointestinal symptoms, it is advisable to consult a healthcare professional for a proper evaluation and diagnosis.

Diagnosis and Tests

The diagnosis of a gastrointestinal stromal tumor (GIST) typically involves a combination of imaging tests, biopsy, and molecular testing. Here are the commonly used diagnostic methods for GIST –

1. Imaging tests

• Computed Tomography (CT) scan – CT scans use X-rays to create detailed cross-sectional images of the abdomen and can help visualize the location, size, and extent of the tumor.
• Magnetic Resonance Imaging (MRI) – MRI uses powerful magnets and radio waves to produce detailed images of soft tissues. It can provide additional information about the tumor’s characteristics and its relation to surrounding structures.
• Endoscopic ultrasound (EUS) – EUS involves the use of an endoscope with an ultrasound probe to obtain images of the gastrointestinal tract. It can help assess the size, location, and depth of invasion of the tumor.

2. Biopsy

• Fine-needle aspiration (FNA) biopsy – This procedure involves using a thin needle to extract a small sample of tissue from the tumor for examination under a microscope. FNA biopsy can help confirm the presence of a GIST and provide information about its cellular characteristics.
• Core needle biopsy – A larger needle is used to obtain a core tissue sample for more extensive analysis.

3. Molecular testing

• Mutational analysis – GISTs commonly have specific genetic mutations in the KIT or PDGFRA genes. Molecular testing is performed on the tumor tissue sample to identify these mutations. It helps determine the subtype of GIST and may guide treatment decisions, as certain mutations respond better to targeted therapies.

4. Endoscopic examination

• Upper gastrointestinal endoscopy – This procedure involves inserting a flexible tube with a camera (endoscope) through the mouth to visualize the esophagus, stomach, and upper part of the small intestine. It helps evaluate the presence and characteristics of GISTs in these areas.

Once a diagnosis of GIST is confirmed, additional tests may be performed to determine the extent of the tumor and the presence of metastasis. These tests may include chest X-rays, positron emission tomography (PET) scans, or laparoscopy (a minimally invasive surgical procedure).

A medical professional for an accurate diagnosis and appropriate management of GIST. They can guide you through the necessary diagnostic tests based on your specific symptoms and clinical presentation.

Treatment

The treatment of gastrointestinal stromal tumors (GISTs) involves a combination of surgical intervention, targeted therapy, and, in some cases, adjuvant chemotherapy. The specific treatment approach depends on various factors such as the tumor size, location, mutational status, risk of recurrence, and the individual’s overall health. Here are the main treatment modalities for GISTs –

1. Surgery

• Tumor resection – Surgical removal of the tumor is the primary treatment for localized GISTs. The goal is to achieve complete resection with negative surgical margins. Depending on the tumor’s size and location, different surgical techniques may be employed, such as wedge resection, segmental resection, total/partial gastrectomy for gastric GISTs, or small bowel resection for small intestinal GISTs. In cases of rectal GISTs, a wide local excision or even abdominoperineal resection may be necessary.

2. Targeted Therapy

• Tyrosine kinase inhibitors (TKIs) – GISTs often have mutations in the KIT or PDGFRA genes, leading to the activation of tyrosine kinase receptors. Targeted therapy with TKIs, such as imatinib (Gleevec), sunitinib (Sutent), or regorafenib (Stivarga), is the standard treatment for advanced or metastatic GISTs, as well as for adjuvant therapy after surgery. These drugs inhibit the activity of the abnormal receptors, slowing down tumor growth and improving patient outcomes. The choice of TKI and treatment duration depends on factors such as mutational status, tumor response, and individual patient characteristics.

3. Adjuvant Therapy

• Adjuvant TKI therapy – In high-risk GISTs or GISTs with a significant risk of recurrence after surgery, adjuvant treatment with TKIs like imatinib may be recommended. It aims to reduce the risk of recurrence and improve overall survival. The duration of adjuvant therapy is typically based on individual risk assessment and patient tolerance.

4. Chemotherapy 

• Chemotherapy is not considered a primary treatment for GISTs. However, it may be considered in rare cases where GISTs do not respond to targeted therapy or in the presence of specific mutations. Chemotherapy drugs such as doxorubicin, ifosfamide, or gemcitabine may be used, but their effectiveness in GISTs is limited.

5. Follow-up and Surveillance

• After treatment, regular follow-up visits and imaging studies are essential to monitor the response to treatment, detect any recurrence or metastasis, and manage potential treatment-related side effects. Follow-up plans may vary based on individual circumstances and healthcare provider recommendations.

The treatment of GISTs should be individualized, and decisions regarding the treatment plan should be made in consultation with a multidisciplinary team of specialists, including medical oncologists, surgeons, and radiologists. They will consider various factors to tailor the treatment approach to the specific needs of each patient.

Outlook

In conclusion, gastrointestinal stromal tumors (GISTs) are rare tumors that develop from the cells of the gastrointestinal tract, particularly the stomach and small intestine. They are characterized by specific genetic mutations in the KIT or PDGFRA genes, which lead to uncontrolled cell growth. 

The outlook for GISTs varies based on factors such as tumor size, location, mitotic rate, mutational status, and the presence of metastasis. Generally, smaller tumors, lower mitotic rates, certain mutations (such as KIT exon 11 mutations), and a good response to targeted therapy are associated with a better prognosis. However, each individual’s prognosis is unique and personalized assessment and treatment planning are crucial.

Advances in targeted therapies, particularly TKIs, have significantly improved the prognosis for GISTs in recent years. Many patients can achieve disease control and long-term survival. Regular follow-up and surveillance are essential to monitor the response to treatment, detect any recurrence, and manage potential side effects.

If you or someone you know is dealing with GISTs, it is important to work closely with a healthcare professional experienced in the management of these tumors. They can provide personalized information, guidance, and support throughout the diagnosis, treatment, and follow-up process.