Laboratory tests cannot specifically diagnose gastrointestinal tumors (GISTs). Usually when individuals seek medical attention for vague symptoms like fatigue or abdominal pain, healthcare providers will request a common series of blood tests to rule out other identifiable causes of fatigue or abdominal pain. These laboratory studies may detect secondary complications related to GIST such as hemorrhaging, obstructions, and bowel perforations.1
A complete blood cell (CBC) count can identify low red blood cell counts that explain anemic fatigue caused by gastrointestinal bleeding or ruptured GISTs which result in bowel perforation.2,3 Coagulation profile tests examine abnormal blood clotting factors related to bleeding problems present in GIST.4 Serum chemistry studies evaluate multiple body systems and detect metabolic, acid-base, or electrolyte disturbances.5 Blood Urea Nitrogen (BUN) and creatinine levels, liver function tests, and amylase and lipase values detect organ dysfunction caused by GIST metastasis to the kidneys, liver, and pancreas, respectively.
A blood type/screen test is performed when the need for a blood transfusion is suspected but uncertain, while crossmatch orders are performed when a blood transfusion due to excessive blood loss is necessary.6 Abnormally low serum albumin levels may indicate malnutrition due to GIST-induced weight loss caused by nausea, vomiting, or bowel obstruction as well as liver disease, kidney disease, or general inflammation.7
Unlike other abdominal neoplasms, GISTs do not cause elevated serum tumor markers. Tumor marker assays may be indicated to identify the presence of other abdominal tumors and differentiate them from GISTs. These assays include cancer antigen 19-9 (CA19-9), cancer antigen-125 (CA-125), carcinoembryonic antigen (CEA), and alpha fetoprotein (AFP).1
Plain abdominal radiography is usually one of the first imaging studies done when a patient with GIST seeks medical care for emergent bowel obstructions or perforations. Abnormal gas patterns related to bowel dilation or the presence of extraluminal air are found with this type of imaging.8
Barium swallow tests may identify the reason for dysphagia in cases of GIST development in the esophagus. Barium enemas identify root causes when individuals with GIST present with constipation, decreased stool quality, or other signs related to the colon or rectum.8 These contrast studies may outline GISTs that protrude into or completely obstruct the lumen of the gastrointestinal tract.
Enteroclysis allows visualization of the small intestine using contrast which may better image small intestinal GISTs.8
Transcutaneous ultrasonography may detect larger GISTs, but the presence of bowel gas, which commonly accompanies GISTs, may obstruct clear imaging. The best ultrasonographic imaging for GIST lesions is obtained through endoscopic ultrasonography.8
Computed tomography (CT) conducted with intravenous or oral contrast material is a critical step in the accurate diagnosis and staging of GISTs. CT scans obtain vital information regarding the location, number, and size of the tumor(s), as well as the impact on and possible metastasis to nearby or even distant viscera, especially the liver.8
Like CT scans, magnetic resonance imaging (MRI) can depict GIST location, size, number of tumors, impact on surrounding viscera, and whether regional or distant metastasis has occurred. MRIs may complement CT scanning in assessment of specific tumor characteristics such as tissue necrosis or signs of older or current hemorrhaging.8
Positron emission tomography (PET) with 2-[F-18]-fluoro-2-deoxy-D-glucose (18 FDG PET) is used to detect GIST metastasis. PET scans primarily evaluate tumor response to treatment with tyrosine kinase inhibitors like imatinib mesylate.8
Endoscopy assesses gastrointestinal bleeding, abdominal pain, or obstruction in individuals with GIST. Endoscopy may reveal submucosa masses displacing surrounding mucosa, ulceration, hemorrhaging, or pressure necrosis, but it can easily miss these tumors, especially if they are smaller. If GIST is suspected prior to endoscopy, it may assist in determining the origin of the tumor.9
Endoscopic ultrasonography (EUS) provides valuable information regarding gastric GIST characteristics and preoperative assessment. It provides a more comprehensive assessment of GISTs and nearby tissues than CT imaging. EUS is the preferred method to biopsy GISTs found in the upper digestive tract. EUS also assists in operative approach planning. GIST characteristics such as size, irregular extraluminal borders, cystic spaces, and echoic patterns.9
Colonoscopy assesses the rectum and colon for GISTs. Neither colonoscopy nor endoscopy can reach all areas within the small intestine, so capsule endoscopy can be used in which the patient swallows a small camera with a light fixture in pill form to take pictures of the small intestine.3
Double balloon enteroscopy (endoscopy) allows for visualization of the small intestine using a special endoscope with two tubes, one contained within the other. A balloon is located on the end of each endoscopic tube. The balloons are repeatedly inflated and deflated to anchor the tubes as they are moved along the GI tract while the physician examines the loops of the small intestine.3
Preoperative biopsy is a controversial topic in the case of GIST. GISTs are predisposed to fragility, hemorrhaging, and rupture which a biopsy may facilitate. Biopsy may also increase the possibility of tumor dissemination. Despite these features which are pertinent specifically to GIST diagnosis, biopsies are required if metastasis is suspected or if there is consideration of adjuvant treatment for a borderline resectable GIST. Biopsy provides definitive GIST diagnosis, and tissue evaluation may inform therapeutic decision making. Needle biopsies performed using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) correctly diagnose up to 80% of GIST cases, while unguided endoscopic biopsies correctly diagnose less than 50% of patients with GIST due to insufficient tumor sampling or completely missing tumors while obtaining only mucosal tissue. If endoscopic biopsy is impossible or inconclusive, percutaneous biopsy sampling using CT or ultrasound guidance through the skin into the tumor might be the optimal approach to obtain this information.9 If samples cannot successfully be obtained via endoscopic or needle biopsy, biopsy may be performed following surgical removal of the GIST.3
GIST Histological Findings
Most often, GIST tumors are highly cellular with an appearance of spindle-shaped cells akin to smooth-muscle tissue, but they lack the normal uniformity of smooth-muscle tissue. There are epithelioid features within the spindle cells. There are several histological considerations when evaluating GIST tumors, including:10
- Mitotic index to determine how rapidly and how many cells are dividing in total
- Presence of necrosis
- Abnormalities of the cell nuclei
- Nuclear-cytoplasmic ratio
- Cell shape
- Quantity of stroma
Histological assessment of GISTs reveals CD117 protein expression (the c-kit protein encoded by the KIT proto-oncogene) as well as the presence of other antigens, including:10
- Nestin (90-100% positivity)
- CD34 (70% positivity)
- Muscle-specific actin
- Smooth-muscle actin
- S-100 protein
- Neuron-specific enolase
- Protein gene product 9.5
Staining methods confirm positive histological identification of the CD117 protein to officially obtain a diagnosis of GIST. CD117 is found in all GISTs and is the most important factor which differentiates GISTs from other GI tumors, such as true smooth-muscle tumors and neural tumors. CD34 expression in about 70% of GISTs indicates a higher likelihood of malignancy, whereas CD44 expression is associated with better outcomes.10
No specific staging system has been decided upon to stage GISTs as the current classification systems are not the most effective methods.11 The most frequently used staging system is the American Joint Committee on Cancer’s (AJCC) tumor-node-metastasis (TNM) classification that stages tumors based on tumor size, the extent of tumor spread to regional areas like lymph nodes, and the presence of distant metastasis. The stages for GISTs range from Stage I to Stage IV.12
Combining the AJCC’s TNM staging system with the criteria of the National Comprehensive Cancer Network (NCCN) may be more beneficial in determining individual risk for progressive disease after margin-negative resection of primary GIST tumors. Risk stratification is performed using the following:11
- Mitotic index (<5 vs >5 per 50 high power field [HPF]) which indicates how rapidly cell division occurs within the tumor
- Tumor size (<2 cm vs > 2cm; <5 cm vs > 5 cm; <10 cm vs > 10 cm)
- Tumor location (gastric or non-gastric)
High mitotic index (> 5/50 HPF) usually indicates malignancy. Low mitotic index of <5/50 HPF is not always indicative of a benign tumor as these GISTs may manifest progressive behaviors. According to several research studies, tumor size larger than 5 cm carries an increased risk for malignancy.11 In general, gastric GISTs are less likely to grow and spread to other regions of the body compared with primary GISTs in other locations.12 However, if the mitotic index of a >10 cm gastric GIST is higher than 5/50 HPF, these GISTs have an equal likelihood of progressive disease (86%) as GISTs in other locations (71-90%). If the mitotic index is <5/50 HPF, regardless of size, gastric GISTs have only a 12% likelihood of progressive disease compared with GIST tumors in other locations (34% to 52%).11
Other histological factors must also be considered when staging GISTs, including presence of necrosis, nuclear atypia, and cellularity of the tumor.
Molecular Genetic Testing
Genetic testing can be performed to search for more common GIST-producing mutations in the KIT or PDGFRA genes, and less commonly the SDH or NF1 genes. This assessment may guide treatment decisions using targeted therapy drugs.3
- Choti, MA. Gastrointestinal stromal tumors (GISTs) workup: laboratory studies. Medscape. Accessed June 18, 2021.
- Complete blood count (CBC) test. WebMD. Accessed June 18, 2021.
- Tests for gastrointestinal stromal tumors. Cancer.org. Accessed June 21, 2021.
- Coagulation profile test. HealthEngine. Published December 13, 2018. Accessed June 18, 2021.
- Russell KE, Roussel AJ. Evaluation of the ruminant serum chemistry profile. Vet Clin North Am Food Anim Pract. 2007; 23(3):403-426, v. doi:10.1016/j.cvfa.2007.07.003
- Pre-transfusion testing. Professional Education. Published June 2, 2016.
- Albumin blood (serum) test. The University of California San Francisco. Accessed June 21, 2021.
- Choti, MA. Gastrointestinal stromal tumors (GISTs) workup: imaging studies. Medscape. Accessed June 18, 2021.
- Choti, MA. Gastrointestinal stromal tumors (GISTs) workup: procedures. Medscape. Accessed June 18, 2021.
- Choti, MA. Gastrointestinal stromal tumors (GISTs) workup: histologic findings. Medscape. Accessed June 18, 2021.
- Choti, MA. Gastrointestinal stromal tumors (GISTs) workup: staging. Medscape. Accessed June 21, 2021.
- Gastrointestinal stromal tumor stages and other prognostic factors. Cancer.org. Accessed June 21, 2021.
Article reviewed by Eleni Fitsiou, PhD, on July 1, 2021.