Gastrointestinal stromal tumor overview: Difference between revisions
Akshun Kalia (talk | contribs) |
Akshun Kalia (talk | contribs) |
||
| Line 39: | Line 39: | ||
==Physical Examination== | ==Physical Examination== | ||
Common physical examination findings of gastrointestinal stromal tumors (GIST) include [[abdominal distension]] and palpable [[abdominal mass]]. Patients with severe and longstanding GIST can present with signs of abdominal [[perforation]] and signs of [[peritonitis]] such as [[abdominal tenderness]], rigidity and [[Abdominal guarding|guarding]]. Other findings include those from tumor rupture and blood loss such as [[low blood pressure]], [[tachycardia]], and [[dyspnea]]. | |||
==Laboratory Examination== | ==Laboratory Examination== | ||
Revision as of 20:01, 18 December 2017
|
Gastrointestinal stromal tumor Microchapters |
|
Differentiating Gastrointestinal stromal tumor from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Gastrointestinal stromal tumor overview On the Web |
|
American Roentgen Ray Society Images of Gastrointestinal stromal tumor overview |
|
Directions to Hospitals Treating Gastrointestinal stromal tumor |
|
Risk calculators and risk factors for Gastrointestinal stromal tumor overview |
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
Around 75 % of the patients with gastrointestinal stromal tumors (GIST) are asymptomatic and the rest have non-specific symptoms such as vague abdominal pain and discomfort. Thus, GIST must be differentiated from other tumors on the basis of cell markers. GIST must be differentiated from other mesenchymal tumors such as gastrointestinal leiomyoma, gastrointestinal leiomyosarcoma, gastrointestinal carcinoma, gastrointestinal schwannoma and melanoma.
Natural History, Complications and Prognosis
If left untreated, patients with gastrointestinal stromal tumors (GIST) may progress to develop abdominal pain, abdominal distension and perforation. A benign GIST may remain unchanged for years before its progression into malignancy. A GIST may rupture and lead to intra-abdominal or gastrointestinal bleeding. Ultimately, the GIST may metastasize and turn fatal. Common complications of GIST include bowel obstruction, bowel perforation, and peritonitis. Depending on the extent of the tumor at the time of diagnosis, the prognosis of GIST may vary. Prognosis of GIST depends upon size, location, spread and mitotic rate of the tumor. A benign GIST treated with surgical resection has much more better outcome as compared to patients with malignant GIST.
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
Obtaining history is an important aspect in making a diagnosis of gastrointestinal stromal tumors (GIST). The areas of focus should be on onset, duration, and progression of symptoms such as abdominal pain, constipation, change in appetite, and black stools. The symptoms of GISTs depends upon the tumor size and location. Majority of the GISTs are asymptomatic. Patients with GIST who have symptoms (tumor size > 5cm) are generally non specific such as dysphagia, vague abdominal discomfort, jaundice and abdominal fullness.
Physical Examination
Common physical examination findings of gastrointestinal stromal tumors (GIST) include abdominal distension and palpable abdominal mass. Patients with severe and longstanding GIST can present with signs of abdominal perforation and signs of peritonitis such as abdominal tenderness, rigidity and guarding. Other findings include those from tumor rupture and blood loss such as low blood pressure, tachycardia, and dyspnea.
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.