Gastric Gastrointestinal Stromal Tumors Workup
- Author: Michael A Choti, MD, MBA, FACS; Chief Editor: N Joseph Espat, MD, MS, FACS more...
Laboratory studies are not diagnostic, and no identifiable tumor markers exist.
See the list below:
Computed tomography scanning of the abdomen: Abdominal CT scanning with intravenous and oral contrast material is a necessary step in the evaluation of these patients. The gastric mass can be detected originating from the gastric wall, as depicted in the image below, but, at times, the organ site of origin is not clear on CT scan. CT scanning can also be used to evaluate tumor invasion to adjacent structures and the presence of intra-abdominal metastasis. The identification of distant disease is important as many as half of patients who initially present with a GIST have distant metastases (two-thirds of whom have hepatic involvement).
Endoscopic ultrasonography: Endoscopic ultrasonography (EUS) can be a valuable tool in the diagnosis and preoperative assessment of gastric GISTs when the diagnosis or location is in doubt but is not generally required for preoperative workup. [15, 16]
- If the location of the lesion is in doubt, the EUS can help plan the operative approach (eg, demonstrating that a proximal gastric lesion on CT scan is far enough away from the GE junction to allow local wedge resection as opposed to total gastrectomy). EUS can also demonstrate the submucosal location of the tumor and can define its size, borders, and echoic pattern.
- In general, ultrasonic features of a mass suspicious for malignancy are large tumors, tumors with irregular extraluminal borders, and the presence of cystic spaces and echogenic foci.
- All gastric GISTs should be considered to have malignant potential. Although, generally, gastric GISTs less than 2 cm tend to behave as "benign" masses, there have been rare reports of distant spread. EUS is generally the preferred modality to facilitate biopsy of the lesion in cases in which biopsy aids in the workup and management of the patient (see Preoperative biopsy).
Upper endoscopy is often the first examination performed in the evaluation of patients with upper gastrointestinal symptoms, but endoscopy is not generally required in the workup of patients with lesions on CT suspicious for a gastric GIST. Gastroscopy may demonstrate a firm, smooth, yellowish submucosal mass, which can be ulcerated, as depicted in the image below.
These tumors can be missed endoscopically because of their frequent submucosal and extraluminal growth. If the diagnosis is suspected prior to endoscopy, an endoscopic ultrasound can be performed to further characterize and help confirm the lesion's growth from the stomach (when the organ site of the tumor is not clearly evident on CT scan), even if not visible endoscopically.
While the diagnosis can often be made using ultrasonographic-guided biopsy, the use of biopsy is controversial in an otherwise primary, resectable lesion suspicious for GIST. Generally, unless a concern for an alternative diagnosis or use of neoadjuvant therapy is being entertained, the use of biopsy is not recommended in this setting (www.nccn.org). The biopsy of a GIST, which tends to be soft and fragile, may cause intratumoral hemorrhage or even rupture and may increase the risk for tumor dissemination. Generally, irrespective of the biopsy results, surgical resection is required for treatment and for definitive diagnosis.
Reasons to perform a biopsy: A biopsy is important and required in the setting of suspected metastatic disease or when neoadjuvant treatment of borderline resectable GIST is being entertained.
- The initial treatment of metastatic GIST should generally be tyrosine-kinase inhibitor therapy with imatinib. Patients with GISTs that appear to involve critical structures or are in challenging locations (eg, duodenal requiring Whipple) may benefit from neoadjuvant therapy. Prior to initiation of imatinib for either metastatic disease or in the neoadjuvant setting, a pretreatment biopsy is generally required to confirm the diagnosis prior to initiation of such treatment.
- Biopsy may also be important when the diagnosis of GIST in is question, such as when the submucosal nature of this tumor is in doubt or when tumor characteristics as demonstrated by upper endoscopy and endoscopic ultrasonography are not typical. In specific patients, such as high-risk operative patients with small benign-appearing lesions and minimal or no symptoms, tissue diagnosis may help in further decision-making.
The 2 ways to obtain a preoperative histologic diagnosis are as follows:
- Endoscopic biopsy: Preoperative endoscopic biopsy may be taken with or without EUS guidance. When taken without the help of EUS, endoscopic biopsy is not accurate and leads to a correct diagnosis in less than 50% of patients. Biopsies may miss the tumor and show only mucosal tissue. In addition, samples from the tumor itself are often too small to establish malignant nature. EUS-guided biopsy is more accurate. This technique can achieve a correct histologic diagnosis in more than 80% of cases and should be performed whenever preoperative histology seems necessary.
- Percutaneous biopsy: Tumor biopsy can be obtained percutaneously under CT scanning or ultrasonographic guidance. Consider this procedure in selected patients when endoscopic biopsy is impossible to perform or the results are negative.
Cellular morphology as visualized by light microscopy can be variable. Most often, the tumors are highly cellular and composed of spindle-shaped cells that resemble smooth-muscle tissue, as depicted in the 1st image below. However, this histologic appearance is not uniform. A similar tumor with a predominant epithelioid component was historically diagnosed as leiomyoblastoma, as depicted in the 2nd image below. This variant is occasionally associated with a well-defined condition called Carney syndrome.
Important histologic factors to consider in evaluating these tumors are mitotic index, cellularity, necrosis, nuclear atypia and nuclear-cytoplasmic ratio, cell shape, amount of stroma, and vascularity.
Investigations of GISTs by immunohistochemistry and electron microscopy (ultrastructural parameters) reveal phenotype variability that includes myoid, neural, and indeterminate characteristics. Study of GISTs by immunohistochemistry methods reveals expression of CD117 and other various antigens, such as nestin (90-100% positivity), CD34 (70% positivity), CD44, vimentin, desmin, muscle-specific actin, smooth-muscle actin, S-100 protein, neurofilament, neuron-specific enolase, and PGP9.5. CD117 plays an important role in the latest specific diagnostic criteria for GISTs. CD117 (c-kit protein) is a growth factor receptor with tyrosine-kinase activity and is a product of the proto-oncogene c-kit. CD117, although not tumor-specific, is expressed in all GISTs but not in true smooth muscle tumors and neural tumors.
CD117 has become a very important tool in the differentiation of GIST from other GI mesenchymal tumors.[21, 22] Positive CD117 staining in a spindle-shaped cell GI tumor is diagnostic for GIST, as depicted in the image below. CD34 is another important diagnostic marker. It is detected in approximately 70% of GISTs, and its presence may indicate a higher probability for a malignant phenotype. CD44 is variably expressed by GISTs, but its expression has been demonstrated to correlate with a better prognosis.
Recent studies suggest that GISTs may originate from the interstitial cells of Cajal. These cells are distributed along the GI tract and play a role in the control of gut motility. The interstitial cells of Cajal exhibit both myeloid and neural features and express the c-kit proto-oncogene receptor. However, the fact that GISTs are detected (although very rarely) outside of the GI tract (ie, omentum, mesentry, retroperitoneum) argues against this hypothesis.
No consensus has been reached regarding a uniform staging system, and none of the currently used classifications is fully satisfactory. Most staging systems employ the 3 most important survival predictors—tumor size, histologic grade, and presence or absence of distant metastatic disease.
The new criteria for risk stratification of primary GIST have been incorporated into the AJCC staging seen below. A study by Rutkowski et al found that the AJCC risk classification after resection of primary GIST is reliable in terms of disease-free survival and overall survival. The study concluded that patients with primary gastric GISTs had better prognosis than those with nongastric GISTs. Primary tumor size and mitotic activity were the most important prognostic factors in terms of disease-free survival in both groups.
The stratification is by mitotic index (5 or less or more than 5 per 50 HPF) and then further divided by tumor size, nodal disease, and tumor metastasis. Gastric GISTs larger than 10 cm but 5 or less per 50 HPF mitotic index have only a 10% risk of progressive disease despite 34-57% risk of progressive disease in the other tumor locations. Gastric GISTs greater than 10 cm and a high mitotic index (>5 per 50 HPF), however, have an equally high risk of progressive disease (86%) as the other tumor locations.
Many studies have shown that tumor diameter greater than 5 cm is associated with increased risk for malignancy. However, relation of size to malignant potential may be gradual, with no clear cut-off point.
The number of mitotic figures is the most accepted index for grade classification, although other histologic parameters, such as cellularity, atypia, and necrosis, are also taken into consideration. A high mitotic index of more than 5 mitoses per 10 HPF usually signifies highly malignant disease. However, a low mitotic index is not always associated with benign course. As many as 25% of tumors with mitotic index of less than 5 mitoses per 10 HPF may manifest an aggressive biological behavior.
See the list below:
TX - Primary tumor cannot be assessed
T0 - No evidence of primary tumor
T1- Tumor smaller than 2 cm, localized
T2 - Tumor 2-5 cm
T3 - Tumor 5-10 cm
T4 - Tumor rupture more than 10 cm in greatest dimension
Regional lymph node
See the list below:
N0 - No regional lymph node metastasis
N1 - Regional lymph node metastasis
See the list below:
M0 - No distant metastasis
M1 - Distant metastases
Table 1. Staging System for Malignant Gastrointestinal Stromal Tumors (Open Table in a new window)
|Group||Tumor Size||Regional Lymph Node||Metastasis||Mitosis|
|Stage IA||T1 or T2||N0||M0||Low|
|Any T||N1||M0||Any rate|
|Stage IV||Any T||Any N||M1||Any rate|
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|Group||Tumor Size||Regional Lymph Node||Metastasis||Mitosis|
|Stage IA||T1 or T2||N0||M0||Low|
|Any T||N1||M0||Any rate|
|Stage IV||Any T||Any N||M1||Any rate|
|Mitoses per 20 HPF||5-Year Survival Rate|
|< 6||< 4||97.5%|