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Gastrointestinal stromal tumors (GISTs) are relatively rare form of benign or malignant tumors which occur in the gastrointestinal (GI) tract, especially in the stomach and small intestine.
GISTs are developed from specialized cells found in the GI tract called interstitial cells of Cajal (ICCs). These cells are the part of autonomic nervous system and regulate GI tract muscle contractions to facilitate the movement of food through the GI tract.
The average age of patients with GIST is 40 to 70 years; however, in some very rare cases, these tumors may affect children and young adults.
In majority of the cases, small GISTs are asymptomatic. Typical signs and symptoms associated with large GISTs include abdominal pain, swelling, nausea, vomiting, loss of appetite, anemia due to bleeding, and weakness.
In most cases, GISTs are not hereditary. Patients without any family history of GIST generally have only one tumor, which is called sporadic GIST.
In contrast, patients with family history of GIST may have multiple tumors (familial GISTs) throughout the GI tract.
Mutations in KIT and PDGFRA genes are primarily associated with GISTs. These mutations are found in both sporadic and familial GISTs. In case of familial GIST, these mutations are inherited in an autosomal dominant manner.
Both KIT and PDGFRA genes encode cell membrane receptors which regulate cell proliferation and survival. Mutations in these genes lead to continuous activation of these receptors, which, in turn, causes abnormal cell growth and tumor formation.
Small GISTs (<2 cm in diameter) are very common and generally asymptomatic. In many cases, these small tumors remain undiagnosed. To perform a histological diagnosis of small tumors, laparoscopic excision is the only feasible way.
Since these tumors are mostly benign in nature, patients with small GISTs are assessed by endoscopic ultrasound and subsequent follow-up. In contrast, large GISTs (≥2 cm in diameter) can be malignant and life‑threatening, if left undiagnosed and untreated.
Diagnostic methods which are performed to detect GISTs are as follows:
Physical examination and family/medical history – a thorough physical examination is done to check possible signs such as abdominal swelling and other health issues. A detailed medical history of the patient including previous medical complications and comorbidities is recorded in addition to patient’s family history.
Computed tomography (CT) scan – it is an X-ray based procedure to take detailed cross‑sectional images of the affected and surrounding areas. It is particularly helpful in detecting the size and location of the tumor, as well as to check tumor metastasis to other parts of the body.
Magnetic resonance imaging (MRI) – this procedure uses radio waves and magnetic field to take detailed images of the affected body areas. It is particularly useful in detecting tumor metastasis to distant organs like the brain and/or spinal cord.
Positron emission tomography (PET) – PET is another useful technique to detect spread of the cancer. This technique is relatively quicker than CT scan and MRI. Hence, it is mainly used to check the efficacy of a particular treatment. It is performed by injecting radioactive sugar molecules, which specifically translocate into cancer cells. Next, images of the radioactive areas are taken with the help of a special type of camera.
Endoscopy – in this technique, a thin, flexible tube (endoscope) with a tiny camera and a light source is inserted through the mouth into the upper GI tract to visualize the inner lining of the tract. A small portion of the tumor can also be removed through the endoscope, and biopsy is performed afterward to evaluate the tumor type.
Colonoscopy – alike endoscopy, a colonoscope (a type of endoscope) is inserted through the anus into the colon to visualize the inner lining of colon and rectum, as well as to take tissue samples for biopsy.
Capsule endoscopy – endoscopy and colonoscopy combined are still not sufficient to take pictures of the entire GI tract. To fulfill this gap, capsule endoscopy is a good option wherein patients need to swallow a capsule containing a tiny camera and a light source. While passing through the GI tract, this capsule takes pictures of the entire tract, including small intestine. Afterward, these pictures are analyzed using a computer.
Endoscopic ultrasound – both endoscopy and ultrasound (a high-energy sound wave) are used together to take images of the upper GI tract.
Immunohistochemistry – after obtaining tumor samples through biopsy, immunohistochemistry is performed to analyze the samples. Antibodies generated against specific cancer-related proteins are used for diagnosing the tumor type in this procedure.
Molecular genetic testing – it is performed to check specific mutations in KIT or PDGFRAgenes, especially in case of familial GIST.
Mitotic rate – this test is performed to check the rate of cancer cell division and growth. It is useful to detect the stage of GIST.