Gastrointestinal stromal tumor

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

In medical oncology, gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal tract. GISTs are non-epithelial tumors and mostly occur in the stomach (70% of cases). 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. GISTs are thought to be derived from the interstitial cells of Cajal or undifferentiated precursor cells that finally develop into interstitial cells of Cajal. Genes involved in the pathogenesis of gastrointestinal stromal tumors include mutations in proto-oncogenes such as c-Kit gene and PDGFRA (platelet derived growth factor receptor-alpha) gene. 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. Common physical examination findings of gastrointestinal stromal tumors (GIST) include abdominal distension, palpable abdominal mass and in severe cases may present with signs of abdominal perforation and peritonitis. CT scan of the abdomen and pelvis is the imaging test of choice and an is important tool in the diagnosis of gastrointestinal stromal tumor (GIST). CT scan may be used to determine the size, location and staging of GIST. A CT scan may also accurately de-mark surrounding structures, multiple tumors and metastases. The predominant therapy for gastrointestinal stromal tumor (GIST) is surgical resection. Medical therapy with tyrosine kinase inhibitors are indicated in patients with unresectable lesions, to decrease tumor size prior to surgery and for prevention of recurrent disease. Imatinib 400 mg to 800 mg PO q24h is the drug of choice for patients with aforementioned conditions. Patients resistant to imatinib are treated with sunitinib 50 mg PO q24h. Medical therapy such as fluid resuscitation, antibiotics cover, deep venous thrombosis prophylaxis should also be given to decrease perioperative morbidity associated with resection of GIST. Patients with GIST on medical therapy, tend to have a recurrent course and must be evaluated on a periodic basis with a CT scan or PET scan for early identification of recurrent disease.

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).

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.

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.

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%).

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.

There is insufficient evidence to recommend routine screening for Gastrointestinal stromal tumor (GIST).

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.

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.

According to the American Joint Committee on Cancer, there are 4 stages of gastrointestinal stromal tumor based on the tumor spread.

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.

Common physical examination findings of gastrointestinal stromal tumors (GIST) include abdominal distension and palpable abdominal mass. Patients with severe and longstanding GIST may present with signs of abdominal perforation and 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.

There are no diagnostic laboratory findings associated with gastrointestinal stromal tumor (GIST). However, patients who present with signs and symptoms of abdominal pain and obstruction and other features of GIST should be evaluated with complete blood cell count, electrolytes, renal function test, liver function tests, coagulation profile, serum amylase and lipase, blood group type and serum albumin levels.

Abdominal X ray is not routinely indicated in patients of gastrointestinal stromal tumor (GIST) as their findings are quite non-specific. However, they may be indicated in patients who present with severe abdominal pain indicating intestinal obstruction or perforation. On an abdominal X-ray, GIST appears as a large, soft tissue density displacing bowel loops. Depending upon the severity of the condition, signs of intestinal obstruction such as multiple air-fluid levels may be present.

CT scan of the abdomen and pelvis is the imaging test of choice and an important tool in the diagnosis of gastrointestinal stromal tumor (GIST). CT scan may be used to determine the size, location and staging of GIST. CT scan may also accurately de-mark surrounding structures, multiple tumors and metastases. On a CT scan, a small GIST (< 5 cms) appears as homogeneous mass with clear boundaries, while a large GIST (>10cms) appears as a heterogeneous mass with irregular borders and have local or distant spread.

MRI is more accurate and sensitive than a CT scan for delineating rectal gastrointestinal stromal tumors (GISTs). For GISTs located at other locations MRI is as sensitive as a CT scan. However, a biopsy (endoscopic or CT guided) is the gold standard in diagnosing GIST. On a T1 weighted MRI, low signal intensity indicates solid component GIST whereas on a T2 weighted MRI, high signal intensity indicates solid component GISTs.

An endoscopic ultrasound (EUS) may be done in patients of gastrointestinal stromal tumors (GIST) presenting with signs and symptoms of abdominal pain, bleeding or obstructive symptoms. EUS-guided biopsy can also be used for diagnosing and staging of GIST. An EUS can detemine the exact cell type and histopathological analysis associated with GIST. On EUS, GIST appears as smooth submucosal mass with areas of ulceration or bleeding.

Endoscopy may be helpful in the diagnosis of gastrointestinal stromal tumor (GIST).An endoscope can be used in conditions where GIST is located in accessible places such as stomach, esophagus and large intestine. On an endoscopy, GIST can appear as a smooth submucosal mass with areas of ulceration or bleeding.

There are no other diagnostic studies associated with gastrointestinal stromal tumors (GIST).

The predominant therapy for gastrointestinal stromal tumor(GIST) is surgical resection. Medical therapy with tyrosine kinase inhibitors are indicated in patients with unresectable lesions, to decrease tumor size prior to surgery and for prevention of recurrent disease. Imatinib 400 mg to 800 mg PO q24h is the drug of choice for patients with aforementioned conditions. Patients resistant to imatinib are treated with sunitinib 50 mg PO q24h. Medical therapy such as fluid resuscitation, antibiotics cover, deep venous thrombosis prophylaxis should also be given to decrease perioperative morbidity associated with resection of GIST.

The predominant therapy for gastrointestinal stromal tumor (GIST) is surgical resection. Surgical resection offers an opportunity to completely cure GIST. Laparoscopic and endoscopic resection are the most preferred route of surgery. Surgical resection of GIST include complete gross resection with an intact pseudocapsule and negative microscopic margins.

Effective measures for the secondary prevention of gastrointestinal stromal tumors include regular follow ups including physical examination with laboratory and imaging evaluations. GIST on medical therapy tend to have a recurrent course and must be evaluated on a periodic basis with a CT scan or PET scan for early identification of recurrent disease.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

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).

The historical perspective of gastrointestinal stromal tumors (GIST) is as follow: ^[1][2][3]

• Prior to the advent and use of electron microscopy, gastrointestinal stromal tumors (GIST) were classified as smooth muscle tumors such as leiomyomas or leiomyosarcomas. However, electron microscopy gave little evidence in the favour of smooth muscle cells as the origin of GIST.
• In 1980s, the use of immunohistochemistry and immunotyping further suggested that GIST arise from antigens related to neural crest cells.
• 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.
• Additional studies have shown that interstitial cells of Cajal express KIT and their development depends upon stem cell factor, which is regulated through KIT kinase.
• In 1998 Hirota and others were the first to describe c-kit (proto-oncogene) mutations as the cause of GIST.
• Recent advances in molecular genetics have to led to classification of GIST based on gene type and development of molecular-targeted therapy.
• In 2001, Joensuu was the first to report successful treatment of patients with advanced GIST on molecular-targeted therapy (imatinib).

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

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 undifferen2tiated 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.

• Gastrointestinal stromal tumors (GISTs) are rare but the most common mesenchymal (nonepithelial) tumors of the gastrointestinal tract.^[1]
• GIST tumors can either be benign tumors or massive malignant tumors with widespread metastasis.
• Earlier GIST were thought to arise from the submucosal or smooth muscle cells of the GI tract. However recent research have proved that GISTs are derived from the interstitial cells of Cajal or undifferentiated precursor cells that finally develop into interstitial cells of Cajal.^[2][3]
  • Interstitial cells of Cajal (ICC) are a normal part of myenteric plexus and the autonomic nervous system of the intestine.
  • Interstitial cells of Cajal serve as a pacemaker of intestine and controls intestinal motility.
  • Molecular analysis has shown that GISTs arising from the interstitial cells of Cajal, stain positive for CD117 (c-KIT) in 90% cases and CD34 in 70% of cases. Around 5% of the cases are positive for PDGFRA. The rest of the cases are defined as wild type (negative for both CD117 and PDGFRA).
    • CD117 is encoded by the KIT gene. Other names for CD117 include proto-oncogene c-Kit and tyrosine kinase receptor Kit.
    • CD34 is the myeloid progenitor cell antigen and also known as hematopoietic progenitor cell antigen CD34.
    • PDGFRA is platelet derived growth factor receptor-alpha and is a tyrosine kinase receptor.
• GIST can occur in any part of the gastrointestinal tract. Thus, GIST vary considerably in their presentation and clinical course, ranging from being asymptomatic to presenting with severe signs and symptoms of bleeding, abdominal pain and perforation.^[4]
  • The most common location for GIST is the stomach with the second most common location as the small intestine.
  • Less frequent sites of occurrence include the colon, rectum and esophagus.
  • Rare sites include pancreas, peritoneum, omentum, or mesentery.
• GIST (tumors) can grow as an endophytic or exophytic lesions.
  • Endophytic lesions are benign linear lesions that grow along the lumen of the affected organ.
  • Exophytic lesions can present as a protruding outgrowth outside the lumen of the GI tract.
• GIST have a variable malignant potential.^[5]
  • About 40% of GISTs that are localized at initial diagnosis give rise to metastasis.
  • Of all GIST, 10%-20% present with distant metastasis with the liver being the most frequent site of metastasis.^[6][7]
  • Other common sites of metastasis include the bone, peritoneum, retroperitoneum, lung, and pleura.

Genes involved in the pathogenesis of gastrointestinal stromal tumors include mutations in c-Kit gene and PDGFRA (platelet derived growth factor receptor-alpha) gene. In some rare cases where the patient do not exhibit the typical c-Kit and PDGFRA mutation, mutation in succinate dehydrogenase (SDH) have been reported. Rare genes involved include BRAF kinase, and protein kinase C. The majority of GISTs are sporadic in origin. ^{[8][9][10][11]}

• The c-kit gene is a proto-oncogene and located on chromosome 4q11-12 (long (q) arm of chromosome 4 at position 12).
  • The c-kit gene encodes for KIT protein which is a transmembrane tyrosine kinase.
  • The KIT protein is located on the cell membrane of certain cell types.
  • Stem cell factor is the ligand that binds to KIT protein, which in turn leads to activation of KIT protein.
  • Upon activation, the KIT protein leads to activation of other intracellular proteins by a process known as phosphorylation (which involves adding oxygen and phosphorus at specific positions).
  • The activation of these intracellular proteins such as (MAP kinase and RAS) plays a vital role in multiple signaling pathways.
  • The signaling pathways stimulated by the KIT protein control many important cellular processes such as cell growth and proliferation.
  • In addition, KIT protein signaling also has a role in the development of gastrointestinal tract cells known as interstitial cells of Cajal.
  • The most commonly observed mutation site in c-Kit gene involves exon 11 leading to a gain-of-function mutation. Less common sites include exons 9 and 13.
  • Gain of function mutation leads to overexpression and autophosphorylation of c-Kit that leads to inhibition of apoptosis and uncontrolled cell proliferation.
  • Almost 90-95% of patients with GIST have mutated c-Kit gene.
  • C-Kit (a tyrosine kinase growth factor receptor) is also the target of medical therapy in GIST; ST-571 (Imatinib; Glivec).
• About 10% cases of GIST are associated with PDGFRA gene.
  • The PDGFRA gene is located on chromosome 4q11-12 (long (q) arm of chromosome 4 at position 12).
  • The PDGFRA gene encodes for the protein; platelet-derived growth factor receptor alpha (PDGFRA), which belongs to a family of proteins known as receptor tyrosine kinases.
    • The platelet-derived growth factor is the ligand that binds to PDGFRA ,which in turn activates the PDGFRA.
    • Upon activation, the PDGFRA leads to activation of other intracellular proteins by a process known as phosphorylation (same as c-Kit explained above).
    • The activation of these intracellular proteins such as (MAP kinase and RAS) plays a vital role in multiple signaling pathways.
    • The multiple signaling pathways stimulated by PDGFRA gene control many important cellular processes such as cell growth and proliferation.
  • The most commonly observed mutation site in PDGFRA gene involves exon 18.
  • As a result of mutation, the PDGFRA gene gets activated on its own and leads to inhibition of apoptosis and uncontrolled cell proliferation.

• Urticaria pigmentosa
• Neurofibromatosis type 1
• Carney-Stratakis syndrome

On gross pathology, GISTs have the following findings:

• Rounded appearance with areas of hemorrhage.
• Large tumors may have necrosis or cystic change.
• Variable size (ranging from 1 to 30cms).

On microscopic histopathological analysis, GISTs are cellular tumors arising from muscularis propria and composed of:^[12]

• Spindle cells (60%-80%): Spindle cells have a fascicular or whorled like appearance and are made of multiple compact cells with minimal stroma and eosinophilic, basophilic or amphophilic cytoplasm. The CD117 expression in spindle cells are generally diffuse and strong.
• Epithelioid cells (20%-30%): Epithelioid tumors are clearly defined with an abundant cytoplasm which is amphophilic to clear. The CD117 expression in epithelioid cells is generally focal and weakly positive.
• Spindle cells or epithelioid cells (10%).

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

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.

Common causes of gastrointestinal stromal tumor include mutation in c-Kit gene and PDGFRA (platelet derived growth factor receptor-alpha) gene. In other cases where the patient do not exhibit the typical c-Kit and PDGFRA mutation, mutation in succinate dehydrogenase (SDH) have been reported. Rare genes involved include BRAF kinase, and protein kinase C. Around 95% of these mutations are sporadic with less than 5% occur as part of hereditary, familial, or idiopathic multi tumor syndromes.^[1][2][3][4]

• The c-kit gene is a proto-oncogene and located on chromosome 4q11-12 (long (q) arm of chromosome 4 at position 12).
  • The c-kit gene encodes for KIT protein which is a transmembrane tyrosine kinase.
  • The KIT protein is located on the cell membrane of certain cell types.
  • Stem cell factor is the ligand that binds to KIT protein, which in turn leads to activation of KIT protein.
  • Upon activation, the KIT protein leads to activation of other intracellular proteins by a process known as phosphorylation (which involves adding oxygen and phosphorus at specific positions).
  • The activation of these intracellular proteins such as (MAP kinase and RAS) plays a vital role in multiple signaling pathways.
  • The signaling pathways stimulated by the KIT protein control many important cellular processes, such as cell growth and proliferation.
  • In addition, KIT protein signaling also has a role in the development of gastrointestinal tract cells known as interstitial cells of Cajal.
  • The most commonly observed mutation site in c-Kit gene involves exon 11 leading to a gain-of-function mutation. Less common sites include exons 9 and 13.
  • Gain of function mutation leads to overexpression and autophosphorylation of c-Kit that leads to inhibition of apoptosis and uncontrolled cell proliferation.
  • Almost 90-95% of patients with GIST have mutated c-Kit gene.
  • C-Kit (a tyrosine kinase growth factor receptor) is also the target of medical therapy in GIST; ST-571 (Imatinib; Glivec).
• About 10% cases of GIST are associated with PDGFRA gene.
  • The PDGFRA gene is located on chromosome 4q11-12 (long (q) arm of chromosome 4 at position 12).
  • The PDGFRA gene encodes for the protein; platelet-derived growth factor receptor alpha (PDGFRA), which belongs to a family of proteins known as receptor tyrosine kinases.
    • The platelet-derived growth factor is the ligand that binds to PDGFRA, which in turn activates the PDGFRA.
    • Upon activation, the PDGFRA leads to activation of other intracellular proteins by a process known as phosphorylation (same as c-Kit explained above).
    • The activation of these intracellular proteins such as (MAP kinase and RAS) plays a vital role in multiple signaling pathways.
    • The multiple signaling pathways stimulated by PDGFRA gene control many important cellular processes such as cell growth and proliferation.
  • The most commonly observed mutation site in PDGFRA gene involves exon 18.
  • As a result of mutation, the PDGFRA gene gets activated on its own and leads to inhibition of apoptosis and uncontrolled cell proliferation.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

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%).

• The incidence of gastrointestinal stromal tumors (GIST) is approximately 1.0-1.60 cases per 100,000 individuals worldwide.^[1]
• In United States, the annual incidence of GIST is approximately 1.54 cases per 100,000 individuals. Every year around 4000-5000 new cases of GIST are reported.
• The incidence of GIST in European nations is relatively similar to other countries. Population based studies have shown the following results:
  • In Iceland, the annual incidence of GIST is approximately 1.2 cases per 100,000 individuals.
  • In Sweden, the annual incidence of GIST is approximately 1.45 cases per 100,000 individuals.
  • In Netherlands, the annual incidence of GIST is approximately 1.2 cases per 100,000 individuals.
  • In Spain, the annual incidence of GIST is approximately 1.09 cases per 100,000 individuals.
• Recent studies have shown that the highest incidence of GIST have been reported in Hong Kong, Taiwan and northern Norway with an estimated 1.90-2.20 cases per 100,000 individuals.

• The prevalence of GIST is approximately 12.9 cases per 100,000 individuals worldwide.^[1]
• With the use of new tyrosine kinase inhibitors such as imatinib, the prevalence of GIST is estimated to go upto 31.8 cases per 100,0000 individuals.^[2]

• Patients of all age groups may develop GIST.
• GIST commonly affects individuals older than 40 years of age with the median age of 60s.
• GIST is extremely rare in patients younger than 30 years of age.

• 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%).
• The SEER study also concluded that Blacks and Hispanics individuals are less likely to develop GIST.^[3]

• Males are more commonly affected by GIST than females.
• The male to female ratio is approximately 1.1 to 1.

• The majority of GIST cases were reported in Hong Kong, Shanghai (China), Taiwan; and northern Norway, with an estimated 19-22 cases per million per year.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

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.

The most potent risk factors in the development of gastrointestinal stromal tumors (GIST) include age and genetic syndromes. Genetic syndromes associated with GIST include neurofibromatosis type 1, Carney-Stratakis syndrome, and familial gastrointestinal stromal tumor syndrome.^[1][2]

• It 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.

• Neurofibromatosis type 1 is an autosomal dominant condition caused by mutation in NF-1 gene. Patients with neurofibromatosis type 1 develop GIST as multiple tumors in the small intestine.

• Carney-Stratakis syndrome is a rare, autosomal dominant condition due to mutation in succinate dehydrogenase enzyme complex. Patients with Carney-Stratakis syndrome have an increased risk of GISTs and paragangliomas. Patients are generally in their second decade of life and more likely to have multiple GISTs.

• Familial gastrointestinal stromal tumor syndrome is a rare, autosomal dominant condition that leads to an increased risk of developing GISTs. These patients have a mutation in their KIT gene (90% cases) or PDGFRA gene (5-10% cases). Patients with familial GIST syndrome develop GIST at an early age and are more likely to have multiple GISTs.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

There is insufficient evidence to recommend routine screening for Gastrointestinal stromal tumor (GIST).

There is insufficient evidence to recommend routine screening for Gastrointestinal stromal tumor (GIST).

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]Parminder Dhingra, M.D. [3]

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.

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.^[1][2][3][4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

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.

• Around 75% patients of gastrointestinal stromal tumors (GIST) are asymptomatic and are diagnosed as an incidental finding on imaging studies done for other reasons.
• If left untreated, patients with GIST may progress to develop abdominal pain, abdominal distension and perforation.
• Depending upon the type of GIST (benign or malignant), a benign GIST may remain unchanged for years before its progression into malignancy.^[1]
• GIST are highly vascular and an untreated tumor may attain massive size leading to rupture and intra-abdominal or gastrointestinal bleeding.
• A ruptured GIST may lead to coffee ground emesis, black stools or even melena.
• Ultimately, the GIST may metastasize and turn fatal.

Common complications of GIST include:^[2]

• Gastrointestinal bleeding
• Bowel obstruction
• Bowel perforation
• Peritonitis
• Volvulus
• Intussusception
• Surgical complications associated with resection include:
  • Atelectasis
  • Pneumonia
  • Urinary tract infection
  • Abscess formation
  • Small-bowel obstruction
  • Deep venous thrombosis

• Depending on the extent of the tumor at the time of diagnosis, the prognosis of GIST may vary.^[3]
• Prognosis of GIST depends upon size, location, spread and mitotic rate of the tumor (mitoses per 50 high-power fields).^{[4][5][6][7][8]}
  • Patients with gastric GIST have been reported to have better outlook as compared to patients with extragastric GIST.
  • Patients with localized primary disease have a average survival period of 5 years.
  • Patients with malignant lesions and metastasis have an average survival period of 1-2 years.
  • Patients with mitotic rate of >10 per 50 HPF have an average survival period of 1.5-2 years
  • Patients with mitotic rate <10 per HPF have an average survival period of 8 years.

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