Malignant gastrointestinal stromal tumours

Overview Of Malignant gastrointestinal stromal tumours

Malignant gastrointestinal stromal tumors (GISTs) are a type of cancer that originates in the gastrointestinal (GI) tract, specifically from the interstitial cells of Cajal, which are part of the nervous system of the GI tract. GISTs can occur anywhere in the digestive system, but they are most commonly found in the stomach (about 60-70% of cases) and small intestine (about 20-30% of cases). Less commonly, they can be found in the esophagus, colon, rectum, or other parts of the digestive tract. GISTs can vary in size and behavior, ranging from benign, slow-growing tumors to highly aggressive malignant tumors. When malignant, GISTs can metastasize (spread) to other organs, most commonly to the liver and peritoneum (the lining of the abdominal cavity). These tumors often present as a mass that may cause symptoms such as abdominal pain, bleeding, or obstruction. Malignant GISTs are characterized by mutations in the **KIT** gene or, less commonly, the **PDGFRA** gene, which lead to abnormal cell growth. The treatment for malignant GISTs typically involves surgical removal and targeted therapies, as these tumors may be resistant to conventional chemotherapy or radiation.

Causes of Malignant gastrointestinal stromal tumours

• The primary cause of malignant gastrointestinal stromal tumors (GISTs) is genetic mutations that occur in the KIT gene (about 80-85% of cases) or the PDGFRA gene (about 5-10% of cases). These mutations lead to the activation of the respective proteins, KIT and PDGFRA, which are receptor tyrosine kinases that regulate cell growth and survival. When these genes mutate, they cause uncontrolled cell division and survival, resulting in the formation of tumors. There are also some known risk factors that increase the likelihood of developing GISTs:
• Genetic Syndromes: Certain inherited conditions increase the risk of developing GISTs, including neurofibromatosis type 1 (NF1), Carney-Stratakis syndrome, and germline mutations in KIT or PDGFRA. In these syndromes, individuals may develop multiple GISTs at a younger age.
• Age: GISTs are most commonly diagnosed in adults, particularly those aged 50-70 years, though they can occur at any age.
• Sex: Men and women are equally affected by GISTs, although some studies suggest a slightly higher incidence in men.
• Prior Radiation Therapy: There may be an increased risk of developing GISTs in individuals who have had prior radiation therapy to the abdomen or pelvis, especially when they are exposed to radiation at a young age.

Risk Factors of Malignant gastrointestinal stromal tumours

• While the exact cause of GISTs remains unclear, several risk factors are associated with an increased likelihood of developing these tumors:
• Genetic Syndromes: Inherited conditions such as neurofibromatosis type 1 (NF1), Carney-Stratakis syndrome, and familial GISTs increase the risk of GIST development due to genetic mutations.
• Age: GISTs are more commonly diagnosed in adults between the ages of 50 and
• Radiation Exposure: Previous exposure to radiation, particularly in childhood or young adulthood, may increase the risk of developing GISTs later in life.
• KIT and PDGFRA Mutations: GISTs caused by mutations in the KIT or PDGFRA genes are more likely to be malignant, and these mutations are considered a key risk factor for the development of GISTs.
• Sex: Although GISTs affect both men and women, some studies suggest a slightly higher incidence in men.

Prevention of Malignant gastrointestinal stromal tumours

• There is no known way to prevent malignant gastrointestinal stromal tumors (GISTs) because the exact cause is largely related to genetic mutations. However, some steps may help with early detection and monitoring:
• Genetic Counseling: Individuals with a family history of genetic syndromes associated with GISTs, such as neurofibromatosis type 1, may benefit from genetic counseling and surveillance to detect early signs of the disease.
• Regular Screening: People at higher risk for GISTs, including those with a known genetic predisposition , may undergo routine imaging or endoscopic evaluations to detect tumors early.
• Avoiding Radiation: Limiting unnecessary radiation exposure, especially in childhood or early adulthood, may help reduce the risk of developing GISTs.

Prognosis of Malignant gastrointestinal stromal tumours

• The prognosis for individuals with malignant gastrointestinal stromal tumors (GISTs) depends on several factors, including the tumor's size, location, mutation type, and whether it has spread.
• Tumor Size: Small tumors that are confined to the GI tract tend to have a better prognosis, while larger tumors or those that have spread to other organs have a worse prognosis.
• Mutations: GISTs with mutations in the KIT gene generally have a better response to targeted therapies like imatinib, while those with PDGFRA mutations may respond less well but still benefit from treatment.
• Metastasis: The presence of metastases, particularly to the liver or peritoneum, is associated with a poorer prognosis. However, treatment with targeted therapies can significantly improve survival rates in patients with metastatic disease.
• Recurrence: Even after successful surgery, GISTs have a high recurrence rate, especially in cases where complete resection was not possible or if the tumor was large. Close follow-up with imaging and monitoring is essential for detecting recurrence early.
• Survival Rates: The five-year survival rate for patients with localized GISTs is generally high, but the prognosis is poorer for those with metastatic disease. Treatment with targeted therapies has significantly improved survival for patients with advanced GISTs.

Complications of Malignant gastrointestinal stromal tumours

• Recurrence: One of the most common complications of GISTs is recurrence, especially in patients who undergo incomplete surgical resection.
• Metastasis: The tumor may spread to distant organs, most commonly the liver and peritoneum. Metastatic GISTs are more difficult to treat and are associated with a poorer prognosis.
• Gastrointestinal Bleeding: Malignant GISTs may cause internal bleeding, leading to anemia and requiring medical intervention.
• Obstruction: Large tumors can cause bowel obstruction, leading to nausea, vomiting, and abdominal pain.
• Surgical Complications: Surgery to remove the tumor carries risks, including infection, bleeding, and injury to surrounding organs.

Related Diseases of Malignant gastrointestinal stromal tumours

• Neurofibromatosis Type 1: This genetic disorder is associated with the development of multiple GISTs, especially in younger individuals.
• Carney-Stratakis Syndrome: A rare inherited condition that results in multiple GISTs and other types of tumors.
• Leiomyosarcoma: A type of cancer that also affects smooth muscle tissue and can be confused with GISTs due to their similar histologic appearance.
• Desmoid Tumors: These are fibrous tumors that can occur in the abdominal wall or other parts of the body and may be mistaken for GISTs due to their slow-growing, fibrous nature.

Treatment of Malignant gastrointestinal stromal tumours

Treatment for malignant gastrointestinal stromal tumors (GISTs) typically involves a combination of surgery, targeted therapies, and sometimes radiation or chemotherapy. The treatment approach depends on the tumor’s size, location, and whether it has metastasized. 1. **Surgical Resection**: Surgery is the primary treatment for localized GISTs. The tumor is usually surgically removed along with some surrounding tissue to ensure that all cancerous cells are excised. The goal is to achieve clear margins to reduce the risk of recurrence. 2. **Targeted Therapy**: Targeted therapies, such as **imatinib** (Gleevec) and **sunitinib** (Sutent), are used to treat GISTs that harbor **KIT** or **PDGFRA** mutations. These drugs inhibit the abnormal tyrosine kinase activity caused by the gene mutations and can shrink or control tumor growth. Targeted therapy is particularly effective for patients with metastatic or inoperable GISTs. 3. **Radiation Therapy**: Radiation is generally not effective for GISTs, as they tend to be resistant to radiation. However, it may be used in some cases to shrink the tumor or relieve symptoms in patients with metastatic disease. 4. **Chemotherapy**: Chemotherapy is not usually effective for GISTs, as these tumors are typically resistant to standard chemotherapy drugs. However, chemotherapy may be considered in rare cases where the tumor has not responded to other treatments. 5. **Clinical Trials**: Participation in clinical trials testing new treatments or combination therapies may be an option for patients with advanced or refractory GISTs.