Gastrointestinal stromal tumor overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2]
Overview
In medical oncology, gastrointestinal stromal tumors (GIST) are a rare tumor of the gastrointestinal tract. GIST is a form of connective tissue cancer, or sarcoma. GISTs are therefore non-epithelial tumors, separate from more common forms of bowel cancer. Majority of the cases occur in the stomach(70%), 20% of cases in the small intestine and less than 10% in the esophagus. Small tumors are generally benign, especially when cell division rate is slow, but large tumors disseminate to the liver, omentum and peritoneal cavity. They rarely occur in other abdominal organs. Gastrointestinal stromal tumor affects men and women equally.
Historical Perspective
Prior to the advent and use of electron microscopy, gastrointestinal stromal tumors (GIST) were classified as smooth muscle tumors such as leiomyomas or leiomyosarcomas. In 1983, Mazur and Clark and Schaldenbrand and Appleman in 1984 were the first to describe gastrointestinal stromal tumors as an independent entity of intra-abdominal tumors that were neither carcinomas nor exhibit histologic features of smooth muscle or nerve cells. In 1998, Kindblom et al described the origin of GIST as pluripotential mesenchymal stem cells which were programmed to differentiate into the interstitial cell of Cajal. In 1998 Hirota and others were the first to describe c-kit (proto-oncogene) mutations as the cause of GIST. In 2001, Joensuu was the first to report successful treatment of patients with advanced GIST on molecular-targeted therapy (imatinib).
Pathophysiology
Gastrointestinal stromal tumors (GISTs) are rare but the most common mesenchymal (nonepithelial) tumors of the gastrointestinal tract. GISTs are derived from the interstitial cells of Cajal or undifferentiated precursor cells that finally develop into interstitial cells of Cajal. GIST tumors can either be benign tumors or massive malignant tumors with widespread metastasis. They can occur in any part of the gastrointestinal tract with the most common location as stomach. GIST (tumors) can grow as an endophytic or exophytic lesions. Genes involved in the pathogenesis of gastrointestinal stromal tumors include mutations in c-Kit gene and PDGFRA (platelet derived growth factor receptor-alpha) gene. Both Kit gene and PDGFRA are tyrosine kinase receptors and control cell proliferation. Mutation in c-Kit gene and PDGFRA leads to inhibition of apoptosis and uncontrolled cell proliferation. In some rare cases where the patient do not exhibit the typical mutation in c-Kit and PDGFRA, mutations in succinate dehydrogenase (SDH) have been reported. Conditions associated with GIST include urticaria pigmentosa, neurofibromatosis type 1, and Carney-Stratakis syndrome. On gross pathology, GISTs have a rounded appearance with areas of hemorrhage. On microscopic histopathological analysis, GISTs are cellular tumors arising from muscularis propria and composed of spindle cells (70%), epithelioid cells (20%) or either one of them.
Causes
Molecular genetics have drastically changed the understanding of gastrointestinal stromal tumors (GIST). Genetic mutations are considered the most identifiable cause of GIST. Around 95% of these mutations are sporadic with less than 5% occur as part of hereditary, familial, or idiopathic multi tumor syndromes. Common causes of gastrointestinal stromal tumor include mutation in c-Kit gene and PDGFRA gene. In other cases where the patient do not exhibit the typical mutation in c-Kit and PDGFRA , mutations in succinate dehydrogenase (SDH) have been reported. Rare genes involved include mutation in BRAF kinase, and protein kinase C.
Epidemiology and Demographics
The incidence of gastrointestinal stromal tumors (GIST) is approximately 1.0-1.60 cases per 100,000 individuals worldwide. The prevalence of GIST is approximately 12.9 cases per 100,000 individuals worldwide. GIST commonly affects individuals older than 40 years of age with the median age of 60s. Males are more commonly affected by GIST than females. A study based on the Surveillance, Epidemiology, and End Results (SEER) registry data found that GIST usually affects individuals of the white race (72.2%).
Risk factors
The most common risk factors in the development of gastrointestinal stromal tumors (GIST) include age and genetic syndromes. Age is considered as the most potent risk factor in the development of GIST with people in the age group of 50-80 believed to be at the highest risk. Genetic syndromes associated with GIST include neurofibromatosis type 1, Carney-Stratakis syndrome and familial gastrointestinal stromal tumor syndrome.
Screening
There is insufficient evidence to recommend routine screening for Gastrointestinal stromal tumor (GIST).
Differential Diagnosis
Gastrointestinal stromal tumor must be differentiated from gastrointestinal leiomyoma, gastrointestinal leiomyosarcoma, gastrointestinal lymphoma / gastric lymphoma, gastrointestinal schwannoma and gastrointestinal carcinoid.
Natural History, Complications and Prognosis
Most common site of involvement of GIST is stomach(70%).
Staging
According to the American Joint Committee on Cancer, there are 4 stages of gastrointestinal stromal tumor based on the tumor spread.
History and Symptoms
Symptoms of gastrointestinal stromal tumor include dysphagia, gastrointestinal hemorrhage, and vague abdominal pain.
Physical Examination
Laboratory Examination
Abdominal X-ray
On abdominal X-ray, gastrointestinal stromal tumor is characterized by soft tissue density displacing bowel loops.
CT scan
Abdominal CT scan may be helpful in the diagnosis of gastrointestinal stromal tumor.
MRI
MRI scan may be helpful in the diagnosis of gastrointestinal stromal tumor.
Ultrasound
Other Imaging Findings
Fluoroscopy may be helpful in the diagnosis of gastrointestinal stromal tumor.
Other Diagnostic studies
Medical Therapy
The predominant therapy for gastrointestinal stromal tumor is surgical resection. Adjunctive chemotherapy/tyrosine Kinase Inhibitor therapy may be required.
Surgical Therapy
The predominant therapy for gastrointestinal stromal tumor is surgical resection. Adjunctive chemotherapy/tyrosine Kinase Inhibitor therapy may be required.