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Gastrointestinal Stromal Tumors Workup

  • Author: Nancy S Behazin, MD; Chief Editor: BS Anand, MD  more...
 
Updated: Mar 30, 2015
 

Laboratory Studies

No laboratory test can specifically confirm or rule out the presence of a GIST. The following tests are generally ordered in the workup of the patient who presents with nonspecific abdominal symptomatology; abdominal pain; or complications of a GIST-like hemorrhage, obstruction, or perforation:

  • Complete blood cell count
  • Coagulation profile
  • Serum chemistry studies
  • BUN and creatinine
  • Liver function tests, amylase and lipase values
  • Type, screen, and crossmatch
  • Serum albumin
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Imaging Studies

Acute abdominal series (plain abdominal radiography)

Plain abdominal radiography is nonspecific but may be ordered as part of the workup of a patient presenting emergently with a possible bowel obstruction or perforation.

Abnormal gas patterns, including dilated loops of bowel or free extraluminal air, are examples of findings that may be detected in these clinical situations.

Barium and air (double-contrast) series

Double-contrast radiographic series can usually detect GISTs that have grown to a size sufficient to produce symptoms.

The choice of performing a barium swallow, barium enema, or both depends on the patient's clinical presentation. For example, patients whose primary symptomatology includes dysphagia should have a barium swallow. Those presenting with constipation, decreased stool caliber, or other signs and symptoms referable to the colon should have a barium enema.

In these contrast studies, GISTs appear as a filling defect that is sharply demarcated and is elevated compared with the surrounding mucosa, as described by Yamashita and colleagues in 2001.[14] Typically, the contour of the overlying mucosa is smooth unless ulceration has developed because of growth of the underlying tumor.

While these studies can produce striking images, frequently the information they provide is limited. Other modalities listed below have equal or greater sensitivity and can provide more information about the status of the surrounding structures.

Enteroclysis

As is frequently the case with other small bowel lesions, GISTs in the small intestine can be difficult to diagnose and localize.

Enteroclysis allows delivery of contrast into the small bowel so it does not become too diluted by the time it reaches the area in question. This may help to better define small intestinal GISTs.

Abdominal ultrasonography

The ultrasonographic appearance of GISTs varies depending on the size of the lesion and the presence or absence of necrosis within the mass. In addition, ulceration or necrosis of the overlying mucosa can change the ultrasonographic characteristics of the tumor.

Transcutaneous ultrasonography is probably not the optimum choice for imaging these lesions unless the mass has reached quite a large size. Because GISTs are associated with air-filled viscera, image quality is often degraded by intervening bowel gas.

The best ultrasonographic images of these lesions are acquired during endoscopic ultrasonography. This is discussed in Procedures.

CT scanning of the abdomen and pelvis

CT scanning is an important radiographic modality in the diagnosis and staging of GISTs. It provides comprehensive information regarding the size and location of the tumor and its relationship to the adjacent structures. CT scanning can also be used to detect the presence of multiple tumors and can provide evidence of metastatic spread.

Ghanem and colleagues, as reported in 2003, performed CT scanning on patients with histologically confirmed primary (n = 20) or recurrent (n = 16) GISTs.[6] These investigators described the CT characteristics of GISTs, dividing them into small (< 5 cm), intermediate (5-10 cm), and large (>10 cm) tumors. Small GISTs were sharply demarcated, homogeneous masses, mainly exhibiting intraluminal growth patterns. Intermediate GISTs were characterized by irregular shape, heterogeneous density, an intraluminal and extraluminal growth pattern, and signs of biological aggression, including adjacent organ infiltration in 9 primary and 2 recurrent lesions. Large GISTs featured irregular margins, heterogeneous densities, locally aggressive behavior, and distant and peritoneal metastases.

Also in 2003, Tateishi and coworkers correlated CT findings with histologic tumor grade and mortality rates.[8] Patients with low-grade (n = 44) and high-grade (n = 25) GISTs underwent dual-phase CT scanning. The investigators found that CT criteria associated with high-grade histology and increased mortality included a tumor larger than 11.1 cm with irregular surface contours, indistinct margins, adjacent organ invasion, heterogeneous enhancement, and hepatic or peritoneal metastasis.

MRI

Similar to CT scanning, MRI can depict the tumor or tumors and provide information about surrounding structures. It can also be used to detect the presence of multiple tumors and metastases.

MRI has not been studied as intensively as CT scanning in the application of diagnosing GISTs. It appears to be just as sensitive as CT scanning.[7]

In 1997, Shojaku and colleagues described a GIST as appearing hypointense on T2-weighted images.[9]

Positron emission tomography scanning with 2-[F-18]-fluoro-2-deoxy-D-glucose

Positron emission tomography scanning has recently been touted as an excellent study for detecting metastatic disease. It has also been used to monitor responses to adjuvant therapies such as imatinib mesylate.

In 2003, Stroobants and colleagues reported on positron emission tomography scanning on 21 patients with soft tissue sarcomas (17 with GISTs) prior to beginning therapy with imatinib mesylate and then 8 days after commencing therapy.[15] Responses were seen on the images in 13 patients with GISTs after 8 days of therapy. The patients underwent CT scanning after a median follow-up of 8 weeks, and CT evidence of responses was seen in 10 of 13 patients. In the patients who demonstrated no response on the day 8 of therapy, positron emission tomography scan image revealed evidence of stable disease or disease progression. The authors concluded that positron emission tomography scanning was a sensitive modality for detecting early clinical response to therapy with imatinib mesylate.

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Procedures

Endoscopy

As a result of GI bleeding, abdominal pain, or GI obstructive symptoms, endoscopy is frequently performed early in the workup of patients with GISTs.

Endoscopic features of GISTs include the suggestion of a smooth submucosal mass displacing the overlying mucosa.

Some tumors may be associated with ulceration or bleeding of the overlying mucosa from pressure necrosis, as described by Pidhorecky and coworkers in 2000.[16]

Obtaining reliable biopsy specimens by traditional endoscopic means is fraught with difficulty because of the submucosal location of these tumors. This is a major reason why endoscopic biopsy results yield a diagnosis in less than 50% of the time. Obtaining a repeat biopsy at the same site as a previous biopsy may increase the diagnostic yield.

Endoscopic ultrasonography

Endoscopic ultrasonography is a modality that allows localization of lesions and their characterization by ultrasonography. Fine-needle aspiration biopsy specimens also may be obtained via the endoscope under sonographic guidance.

The typical endoscopic ultrasonographic appearance of a GIST is a hypoechoic mass situated in the layer corresponding to the muscularis propria.

In 1997, Chak and coinvestigators described endoscopic ultrasonographic characteristics of malignant GISTs to include size larger than 4 cm, heterogeneous echogenicity, internal cystic areas, and irregular borders on the extraluminal surfaces.[17]

In 2002, Belloni and colleagues compared CT scanning and endoscopic ultrasonography in the diagnosis of GIST and in their ability to discriminate benign from malignant disease.[18] They found that endoscopic ultrasonography is more accurate in differentiating benign from malignant lesions but that CT scanning allows a more comprehensive evaluation of the mass and the surrounding structures. The authors concluded that the techniques are complementary and helpful in planning operative therapy.

Kim et al reported that EUS may be able to differentiate gastric GISTs from leiomyomas in a study of 53 patients.[19] The findings of inhomogenicity, hyperechogenic spots, a marginal halo, and higher echogenicity as compared with the surrounding muscle layer appeared more frequently in the GISTs than in the leiomyomas (P < 0.05). The presence of at least 2 of these 4 features had a sensitivity of 89.1% and a specificity of 85.7% for predicting GISTs. Except for tumor size and irregularity of the border, most of the EUS features were not helpful for predicting the malignant potential of GISTs. On multivariate analysis, only the maximal diameter of the GISTs was an independent predictor. The investigators also reported that once GISTs are suspected, surgery should be considered if the size is greater than 3.5 cm.

It has been suggested that definitive diagnosis of GIST requires tissue acquisition through EUS-guided fine needle aspiration. However, biopsy may not be necessary if the tumor is surgically resectable and preoperative medical therapy is not required. Biopsy may be required when preoperative therapy is needed in cases where the tumor is unresectable or only marginally resectable.

Angiography

Angiography is rarely used in the diagnosis or management of GISTs. It may be used during diagnostic dilemmas or for urgent treatment of complications such as GI hemorrhage. Therefore, much of the literature on GISTs and angiography is limited to case reports.

In 1996, Gordon and coworkers reported on the use of angiography to help localize a GIST in the right lower abdominal quadrant.[20]

Also in 1996, Au and Peh reported on a patient with melena and anemia in whom angiography delineated an ileal GIST.[21]

In 2003, Nakagawa and coinvestigators and Suzuki and colleagues used angiography to localize extragastric GISTs in the greater omentum.[22, 23]

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Histologic Findings

GISTs manifest a wide variety of clinical behavior, from slow-growing indolent tumors to aggressive malignant cancers with the propensity to invade the adjacent organs, metastasize to the liver, and recur locally within the abdomen. Clinical presentation provides the most overt evidence for distinguishing benign from malignant behavior. Histologic analysis of biopsy or operative specimens provides objective measures for diagnosis and helps predict clinical behavior.

The morphologic features that appear to be the most predictive of outcome and biological behavior are tumor size and the mitotic rate. Unfortunately, no absolute determinations can be made because even small lesions with low mitotic rates can metastasize or behave in a locally aggressive fashion. In 2002, Fletcher and colleagues proposed a classification system to define relative risk for malignant behavior in GISTs.[24] See the Fletcher et al stratification of risk in Prognosis.

GISTs typically stain intensely for the CD117 molecule, which is an epitope of KIT. In contrast, desmoids, schwannomas (S-100–positive, KIT-negative), leiomyomas, and leiomyosarcomas (desmin-positive, KIT-negative) do not. In GISTs, according to Fletcher et al, CD117 appears diffusely in the cytoplasm in a punctate or Golgi-like pattern.[24] CD34 staining results are also positive in approximately 60% of GISTs. In a Korean study, Koh et al concluded that the lack of CD34 expression may be the result of cystic degeneration following treatment with imatinib.[25]

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Staging

Woodall et al created a staging system based on 2537 patients with GISTs from 1977-2004 reported to the SEER database.[26] A TGM (tumor, grade, metastasis) staging system was created and survival data were analyzed using Kaplan-Meier methods, log-rank analyses, and Cox regression models. Median follow-up time was 21 months, and 47.6% of patients were men. Median age was 64 years, 5% had lymph node involvement, and 22.6% had distant metastasis. Tumor size (T1, ≤ 70 mm; T2, >70 mm; P < .001), grade (G1, grades I and II; G2, grades III and IV; P < .001), and the presence of metastases (M0, no; M1, yes; P < .001) did affect the overall survival. When combined in a TGM staging system, the grade and the presence of metastasis were the factors most predictive of survival.

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Contributor Information and Disclosures
Author

Nancy S Behazin, MD Fellow, Department of Gastroenterology, Scott and White Hospital, Texas A&M Health Science Center College of Medicine

Nancy S Behazin, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Medical Association, American Society for Gastrointestinal Endoscopy, Texas Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Noel Williams, MD, FRCPC FACP, MACG, Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada

Noel Williams, MD, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Acknowledgements

Robert A Decker, MD Clinical Assistant Professor, Department of Medicine, University of Hawaii at Manoa: Chief, Gastroenterology Service, Kaiser Permanente Medical Center of Honolulu

Disclosure: Nothing to disclose.

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Michael AJ Sawyer, MD Consulting Staff, Department of Surgery, Southwestern Medical Center; Consulting Staff, Department of Surgery, Comanche County Memorial Hospital; Consulting Staff, Great Plains Surgical Clinic, Inc

Michael AJ Sawyer, MD is a member of the following medical societies: American College of Surgeons, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, and Society of Laparoendoscopic Surgeons

Disclosure: Nothing to disclose.

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