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Practice Essentials
Gastrointestinal stromal tumors (GISTs) account for less than 1% of gastrointestinal tumors, but they are the most
common mesenchymal neoplasms of the gastrointestinal tract. GISTs are usually found in the stomach or small
intestine but can occur anywhere along the GI tract and rarely have extra-GI involvement.
[1, 2]
Diagnosis
No laboratory test can specifically confirm or rule out the presence of a GIST. The following tests are generally
ordered in the workup of patients who present with nonspecific abdominal symptoms; abdominal pain; or
complications of a GIST-like hemorrhage, obstruction, or perforation:
Complete blood cell count
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Coagulation profile
Serum chemistry studies
BUN and creatinine
Liver function tests and amylase and lipase values
Type and screen, type and crossmatch
Serum albumin
Imaging studies
Plain abdominal radiography:
Nonspecific
May be part of an emergent workup
Abnormal gas patterns, including dilated loops of bowel or free extraluminal air, may be seen with bowel
obstruction or perforation
Barium and air (double-contrast) series:
Frequently provides only limited information
Can usually detect GISTs that have grown to a size sufficient to produce symptoms
Barium swallow for patients with dysphagia
Barium enema for patients with constipation, decreased stool caliber, or colonic manifestations
[3]
Sharply demarcated
Homogeneous density
Mainly exhibit intraluminal growth patterns
[4]
Irregular shape
Heterogeneous density
An intraluminal and extraluminal growth pattern
Signs of biological aggression, sometimes including adjacent organ infiltration
[4]
[4]
Irregular margins
Heterogeneous densities
Locally aggressive behavior
Distant and peritoneal metastases
[5]
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Less well studied than CT for diagnosing GISTs, but appears equally sensitive
[7]
Positron emission tomography scanning with 2-[F-18]-fluoro-2-deoxy-D-glucose has the following uses:
Detection metastatic disease
Monitoring of response to adjuvant therapy (eg, imatinib mesylate)
Endoscopy:
Frequently performed early in the workup of patients with GI bleeding, abdominal pain, or GI obstructive
symptoms from GISTs
Endoscopic features of GISTs include the suggestion of a smooth submucosal mass displacing the overlying
mucosa
[8]
Ulceration or bleeding of the overlying mucosa from pressure necrosis may be present
Problematic for biopsy specimen collection because of the submucosal location of GISTs
Endoscopic biopsy results yield a diagnosis in less than 50% of cases
Obtaining a repeat biopsy in the same site as a prior biopsy may increase the diagnostic yield
Endoscopic ultrasonography (EUS):
Allows localization of lesions and their characterization by ultrasonography
Fine-needle aspiration biopsy specimens may be obtained under sonographic guidance
GISTs typically appear as a hypoechoic mass in the layer corresponding to the muscularis propria
[9]
Complementary with CT
More accurate than CT in differentiating benign from malignant lesions
Allows a more comprehensive evaluation of the mass and the surrounding structures than CT
[10]
EUS features that may help differentiate gastric GISTs from leiomyomas are as follows
Inhomogenicity
Hyperechogenic spots
A marginal halo
Higher echogenicity than the surrounding muscle layer
Aspects of EUS-guided biopsy are as follows:
Biopsy provides definitive diagnosis
Biopsy may be required when preoperative therapy is needed in cases where the tumor is unresectable or
only marginally resectable
Biopsy may not be necessary if the tumor is surgically resectable and preoperative medical therapy is not
required
See Workup for more detail.
Management
Surgery is the definitive therapy for patients with GISTs, as follows:
Radical and complete surgical extirpation offers the only chance for cure
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Surgery is also indicated in symptomatic patients with locally advanced or metastatic disease
Debulking large lesions is helpful when adjuvant therapy is contemplated
Laparoscopic resection has improved and is a more frequently considered option
Imatinib mesylate is used in GIST as follows:
Adjuvant therapy post complete surgical resection in patients with high-risk tumors
Neoadjuvant therapy with goal of tumor shrinkage prior to surgical resection
Other tyrosine kinase inhibitors used when imatinib is not tolerated or not effective are as follows:
Sunitinib: Less specific than imatinib; approved as a second-line agent for advanced GIST
Sorafenib: Investigational second-generation agent
Dasatinib: Investigational second-generation agent
Nilotinib: Investigational second-generation agent
See Treatment and Medication for more detail.
Background
Gastrointestinal stromal tumors (GISTs) account for less than 1% of gastrointestinal tumors, however, are the most
common mesenchymal neoplasms of the gastrointestinal tract. GISTs are usually found in the stomach or small
intestine but can occur anywhere along the gastrointestinal tract and rarely have extragastrointestinal
[12]
involvement.
GISTs rank a distant third in prevalence behind adenocarcinomas and lymphomas among the
histologic types of gastrointestinal tract tumors.
Historically, these lesions were classified as leiomyomas or leiomyosarcomas because they possessed smooth
muscle features when examined under light microscopy. In the 1970s electron microscopy found little evidence of the
smooth muscle origin of these tumors. In the 1980s, with the advent of immunohistochemistry, it was shown that
these tumors did not have immunophenotypic features of smooth muscle cells and rather expressed antigens related
to neural crest cells. Mazur and Clark in 1983, and Schaldenbrand and Appleman in 1984 were the first to describe
"stromal tumors" as a separate entity.
According to the work of Kindblom and associates reported in 1998, the actual cell of origin of GISTs is a
[13]
pluripotential mesenchymal stem cell programmed to differentiate into the interstitial cell of Cajal.
These are GI
pacemaker cells found in the muscularis propria and around the myenteric plexus and are largely responsible for
initiating and coordinating GI motility. This finding led Kindblom and coworkers to suggest the term GI pacemaker cell
[13]
tumors.
Additional studies found that interstitial cells of Cajal express KIT and are developmentally dependent on
stem cell factor, which is regulated through KIT kinase. Perhaps the most critical development that distinguished
GISTs as a unique clinical entity was the discovery of c-kit proto-oncogene mutations in these tumors in by Hirota
and colleagues in 1998.
[14]
These advances have led to the classification of GISTs as an entity separate from smooth muscle tumors, helped
elucidate their etiology and pathogenesis at a molecular level, and led to the development of molecular-targeted
therapy for this disease.
Pathophysiology
GISTs can occur anywhere in the gastrointestinal tract. They are submucosal lesions, which most frequently grow
endophytically in parallel with the lumen of the affected structure. GISTs may also manifest as exophytic extraluminal
excrescences. These tumors have been reported ranging in size from smaller than 1 cm to as large as 40 cm in
[15]
diameter.
Approximately 50-70% of GISTs originate in the stomach. The small intestine is the second most
common location, with 20-30% of GISTs arising from the jejunoileum. Less frequent sites of occurrence include the
colon and rectum (5-15%) and esophagus (< 5%). Primary pancreatic, omental, or mesenteric GISTs have been
reported but are very rare.
[12]
Frequency
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United States
Roughly 5000 new cases of gastrointestinal stromal tumors are diagnosed annually in the United States.
International
Population-based studies from Iceland, the Netherlands, Spain, and Sweden report annual incidence rates ranging
from 6.5 to 14.5 cases per million.
Mortality/Morbidity
Outcomes in patients with GISTs are highly dependent on the clinical presentation and the histopathological features
of the tumor. The overall 5-year survival rate ranges from 28-60%. This can be stratified for patients presenting with
localized primary disease and those presenting with metastatic or recurrent disease. The median survival rate in the
former group is 5 years, while the median survival rate in the latter group is approximately 10-20 months. Larger
GISTs are associated with complications such as GI hemorrhage, GI obstruction, and bowel perforation. This is
discussed further in Surgical Care and Complications.
Tumors can be classified into high and low-risk categories based on size, location, and mitotic activity. The
implications of these tumor characteristics are discussed in Prognosis and Histologic Findings.
Race
GISTs have no known racial proclivity. However, Cheung et al reported that out of 3795 patients diagnosed with
mesenchymal tumors from the Surveillance, Epidemiology, and End Results (SEER) database from 1992-2005,
more than 88% of tumors were identified as GIST with patient demographics as follows: 72.2% Caucasians, 15.6%
[3]
Sex
SEER (Surveillance, Epidemiology, and End Results) data from 1992-2000 report a slightly higher prevalence in
[4]
Age
GISTs have been reported in all age groups including infants. It is extremely rare in patients younger than 30 years.
[15]
In a study of 1765 gastric GISTs, the median age at diagnosis was 63 years.
[5]
and ileal GISTs, the mean age was 59 years. In the latter 2 series, only 2.7% of gastric GISTs and 0.6% of small
bowel GISTs were detected in patients younger than 21 years.
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