Gastrointestinal stromal tumors, often called GISTs, are a specific type of soft tissue sarcoma that originates in the digestive system. These tumors can form anywhere along the gastrointestinal tract, from the esophagus to the rectum, though they are most frequently found in the stomach and small intestine. While GISTs are considered rare, with an estimated 5,000 to 6,000 new cases diagnosed annually in the United States, understanding their nature and how they differ from other digestive system cancers is important.
Understanding Gastrointestinal Stromal Tumors
GISTs arise from specialized cells within the wall of the gastrointestinal tract known as interstitial cells of Cajal (ICCs). These ICCs function as the “pacemaker cells” of the gut, regulating the rhythmic contractions that move food through the digestive system. GISTs are distinct from more common gastrointestinal cancers, such as adenocarcinomas, which originate from glandular cells lining the digestive tract. Unlike adenocarcinomas, GISTs develop in the muscle layers of the digestive organs.
The most common locations for GISTs are the stomach, accounting for approximately 51-55% of cases, and the small intestine, making up about 29-36%. Less common sites include the colon (3-7%), rectum (3-5%), and esophagus (0.5-1%). All GISTs have the potential to metastasize, with risk varying by tumor size and location. The growth of most GISTs is driven by specific genetic mutations, primarily in the KIT or PDGFRA genes. These mutations cause encoded tyrosine kinase proteins to become overactive, leading to uncontrolled cell growth.
Identifying Potential Symptoms
GIST symptoms vary depending on tumor size and location within the digestive tract. Many small GISTs cause no noticeable symptoms and are sometimes discovered incidentally during medical evaluations. As a GIST grows, common indicators include abdominal pain or discomfort, often the first symptom with larger tumors.
Digestive system bleeding is another common symptom, manifesting as black or tarry stools, or blood in vomit. This bleeding can lead to fatigue or weakness due to anemia. Other symptoms might include nausea, vomiting, a feeling of fullness after eating only a small amount of food, or a palpable mass in the abdomen. If the tumor is located in the esophagus, difficulty swallowing may occur. These symptoms are not exclusive to GISTs and can be caused by other less serious conditions, making accurate diagnosis challenging.
Diagnostic Procedures
Diagnosing GISTs involves imaging and tissue analysis to confirm a tumor’s presence and characteristics. Imaging studies, such as computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, and sometimes positron emission tomography (PET) scans, are used to assess the tumor’s size, exact location, and whether it has spread to other areas of the body, such as the liver or peritoneum. These scans provide detailed images that help visualize the tumor within the digestive tract.
Endoscopic procedures, including upper endoscopy or colonoscopy, are also performed to directly visualize the inside of the digestive tract. An endoscopic ultrasound (EUS) is often used in conjunction with endoscopy to provide detailed images of the tumor within the layers of the gastrointestinal wall and to guide a biopsy.
A definitive diagnosis of GIST requires a biopsy, where a small tissue sample is taken from the tumor. This tissue is then examined under a microscope by a pathologist. Specialized immunohistochemical staining, particularly for markers like CD117 (KIT) and DOG1, is performed on the biopsy sample to confirm the diagnosis of GIST and differentiate it from other types of tumors. Genetic testing of the tumor tissue is also performed to identify specific mutations in genes like KIT or PDGFRA, which is important as these mutations guide treatment decisions.
Treatment Options
Surgical removal is the primary treatment for localized GISTs, aiming for complete tumor resection. Even after successful surgery, recurrence or metastasis may occur in at least 50% of patients within two years. The likelihood of recurrence is influenced by factors such as the tumor’s size, mitotic rate (how quickly cells are dividing), and its location, with larger tumors in the small intestine having a higher risk.
Targeted therapy, using tyrosine kinase inhibitors (TKIs), plays a significant role in GIST treatment. Imatinib (Gleevec) is a commonly used TKI that specifically targets the KIT or PDGFRA mutations that drive GIST growth. This medication works by blocking the signals that tell cancer cells to grow and divide. Imatinib can be used as neoadjuvant therapy before surgery to shrink larger tumors, making them easier and safer to remove; as adjuvant therapy after surgery to reduce recurrence risk; and for advanced or metastatic disease to control tumor growth.
If imatinib resistance develops, other TKIs like sunitinib or regorafenib may be used. The specific KIT or PDGFRA mutation identified in the tumor can influence its sensitivity to these targeted therapies. For instance, some PDGFRA mutations, like the exon 18 D842V mutation, may be resistant to imatinib. Unlike many other cancers, traditional chemotherapy and radiation therapy are generally ineffective for GISTs due to their unique biological characteristics. Treatment decisions are individualized, considering tumor characteristics, mutation status, and disease localization or spread.
Life After Treatment and Monitoring
Following GIST treatment, long-term follow-up and monitoring are important due to recurrence potential. Patients undergo regular imaging scans, such as CT scans, to detect any tumor return. This ongoing surveillance is necessary because GISTs can recur years after successful initial treatment.
Adjuvant therapy, often imatinib taken for several years after surgery, is prescribed to reduce recurrence risk, especially for higher-risk tumors. This prolonged medication suppresses any remaining microscopic cancer cells. Managing potential side effects from long-term medication is also a consideration for quality of life. Patients benefit from a multidisciplinary care team that includes oncologists, surgeons, and other specialists to provide comprehensive and coordinated care throughout their recovery and monitoring period.