eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract
Intestinal Stromal Tumors: Differential Diagnoses & Workup
Updated: Sep 11, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Carcinoid Tumor, Intestinal
Granular Cell Tumors
Lipomas
Malignant Melanoma
Mesenteric Tumors
Metastatic Cancer, Unknown Primary Site
Other Problems to Be Considered
Stomach
Adenocarcinoma
Lymphoma
Schwannoma
Desmoid fibromatosis
Smooth muscle neoplasm (leiomyoma, leiomyosarcoma)
Neuroendocrine neoplasms such as gastric carcinoid
Primary adenocarcinoma
Metastatic lesions to small bowel, especially melanoma
Lymphoma
Mesenteric tumors invading into small bowel (mesenteric fibromatosis, inflammatory pseudotumor, lymphoma, sclerosing mesenteritis, and metastatic disease)Colon
Adenocarcinoma
Lymphoma
Metastatic melanoma
LeiomyosarcomaAnorectum
Adenocarcinoma
Squamous cell carcinoma of the anus
Lymphoma
Malignant melanoma
CarcinoidEsophagus
Adenocarcinoma
Squamous cell carcinoma
Leiomyoma, leiomyosarcoma
For intraluminal masses: carcinoma, papilloma, adenoma, and inflammatory or fibrovascular polyp
For small lesions in the esophageal wall: lipoma, granular cell tumor, duplication cystMesentery and omentum
Sarcoma (liposarcoma, leiomyosarcoma, malignant fibrous histiocytoma, fibrosarcoma)
Mesenteric fibromatosis
Inflammatory pseudotumor
Workup
Laboratory Studies
- Conduct a complete preoperative workup including blood panel, complete metabolic panel, and coagulation factors.
- Based on the location, size, and imaging studies of the GIST, other laboratory workup can include tumor markers for other abdominal neoplasms: CA19-9, CEA, CA-125, AFP. GISTs are not associated with an elevation of any serum tumor markers.
Imaging Studies
- Clinical pretherapeutic evaluation for GISTs is very similar to that pursued for other GI malignancies. Note that the appropriate imaging workup depends on the size and location of the tumor.
- Characteristic findings on computed tomography (CT) scan and magnetic resonance imaging (MRI) can be highly suggestive of a GIST versus other GI malignancies.
- Computed tomography (CT) study of the abdomen and pelvis with oral and IV contrast is the most essential study to assess primary tumor extension and presence of metastasis, especially in the peritoneum or liver. On oral and intravenous CT scans, the intramural component of GIST is typically evident, though it may be more difficult for large masses with extension into adjacent structures. Most of the tumors show peripheral enhancement with central areas of low attenuation suggesting hemorrhage, necrosis, or a cystic component. Typically, the enhancement is heterogenous. Cavitary lesions may be present with air fluid levels. Metastatic lymphadenopathy is not a feature of GISTs. Metastatic disease may be evident with CT findings consistent with organ invasion, ascites, omental or peritoneal spread, or liver metastasis.
- Magnetic resonance imaging (MRI) can also be very helpful. MRI findings can be variable. Based on the degree of necrosis and hemorrhage, the signal intensity pattern can vary. Solid tumor portions show low intensity on T1 images and high intensity on T2 images with enhancement of the mass upon intravenous gadolinium. Hemorrhagic components of the tumor can vary from high to low signal intensity based on the age of the hemorrhage. MRI can be an especially helpful adjunct to CT in the evaluation of large tumors with hemorrhagic and necrotic components to them. Barium and Gastrografin studies of the stomach, small intestine, and colon aid in the diagnosis of GISTs. These studies include upper gastrointestinal series, small bowel series, and barium enema studies. Typically, the lesions have the classic features of submucosal masses such as leiomyomas and leiomyosarcomas. They appear as a smooth-lined filling defect in the lumen with well-demarcated borders. Sixty percent of the time, focal areas of
- Ultrasonography may suggest the presence of a malignant GIST, marked by cystic spaces, echogenic foci, and irregular extraluminal borders. Ultrasonography has no benefit compared to CT or MRI; therefore, the former modality is rarely used if the latter two provide sufficient information for a tentative diagnosis.
- Fluorodeoxyglucose positron emission tomography (FDG-PET) scanning may be helpful in the staging and evaluation of GISTs. Its value has been reported in studying disease progression or response to therapy in people receiving imatinib for primary or metastatic GISTs.
Procedures
Procedures performed in the evaluation of GISTs are similar to those used for other GI malignancies. Base the choice of procedure on the location and size of the mass and the need for any further information after pursuing imaging modalities.
For tumors of the upper GI tract, esophagogastroduodenoscopy may aid in the extent of intraluminal involvement and in obtaining definitive tissue diagnosis. Typically, they appear as a submucosal mass. Any endoscopic biopsy, however, needs to be deep enough to obtain tissue below the mucosa.
GISTs typically appear as a smooth protrusion of the bowel wall with preserved mucosal lining and may have components of ulceration and bleeding. Endoscopic ultrasonography may show a hypoechoic mass originating in the muscularis propria of the bowel wall. Similarly, anorectal ultrasonography and colonoscopy can provide findings consistent with GISTs of the colon, rectum, and anus.
Histologic Findings
On histology, spindle-shaped cells are most common (70%), followed by epithelioid cells (20%) and a mixed spindle cell-epithelioid pattern. The tumor cells are highly cellular with less eosinophilic cytoplasm than smooth muscle neoplasms. They have indistinct cell margins and minimal tumor stroma. Malignancy is associated with histology consistent with nuclear atypia, high cellularity, high mitotic rate (more than 5 per HPF), mucosal invasion, necrosis, and a mixed spindle cell-epithelioid morphology (see Images 3-4).
GISTs are distinguished from leiomyomas and leiomyosarcomas by immunohistochemistry and electron microscopy. Unlike the latter two, GISTs are usually positive for CD34 (60-70%). They may be positive for smooth muscle actin, but unlike smooth muscle tumors, GISTs are rarely positive for desmin. Unlike smooth muscle neoplasms, GISTs may not have thin actin filaments with periodic densities on electron microscopy. The hallmark of GISTs is their positivity for CD117 (KIT) receptor, the product of c-kit proto-oncogene. Gain of functional mutations of the KIT protein, a tyrosine kinase receptor, is believed to play a critical role in the oncogenesis of GISTs. Although other tumors can be positive for CD117, most of these tumors do not occur in the GI tract (see Image 5).
The above information helps distinguish GISTs from other GI neoplasms, but assigning the risk of malignancy to these tumors can still be difficult. Many tumors are graded as having low malignant potential due to this difficulty. Fletcher et al (2002) proposed a risk assessment strategy (Table 2).8
Table 2. Risk Stratification of GIST Based on HistologyOpen table in new window
Table
| Size, cm | Mitotic Count per 50 Cells on HPF | Risk Assignment |
|---|---|---|
| <2 | <5 | Very low |
| 2-5 | <5 | Low |
| <5 | 6-10 | Intermediate |
| 5-10 | <5 | Intermediate |
| >5 | >5 | High |
| >10 | Any | High |
| Any | >10 | High |
| Size, cm | Mitotic Count per 50 Cells on HPF | Risk Assignment |
|---|---|---|
| <2 | <5 | Very low |
| 2-5 | <5 | Low |
| <5 | 6-10 | Intermediate |
| 5-10 | <5 | Intermediate |
| >5 | >5 | High |
| >10 | Any | High |
| Any | >10 | High |
Staging
No absolute consensus has been reached on a staging system for GISTs. Although there is a staging system for sarcomas, it is not helpful in accurately staging GISTs. A risk assessment for malignant potential of GISTs is available that is based on the tumor size and mitotic index on histology. Overall, assessing the malignant potential of GISTs remains difficult.
Even small GISTs are often read as having low malignant to uncertain malignant potential. The tumor location changes the criteria used to predict biological behavior, which further complicates determining the malignant potential. Tumors originating from the small bowel, mesentery, colon, and rectum are often associated with a less favorable outcome than those associated with the stomach. The two most important prognostic predictors of behavior are tumor size and mitotic index on histology. Of course, overt metastasis is a clear indication of malignancy.
Tumors of the esophagus and colon are generally malignant, whereas gastric GISTs are more frequently indolent tumors. GISTs larger than 5 cm are generally malignant, whereas almost all incidentally detected GISTs (<1 cm) are typically benign. No exact cut-off diameter that accurately predicts malignancy, in addition, diameter can be variable based on tumor location.
The mitotic rate is another important factor that helps predict biological behavior of GISTs. As shown in Table 2, mitotic rate and tumor size could be used to provide a general idea of the malignant potential of a GIST.
More on Intestinal Stromal Tumors |
| Overview: Intestinal Stromal Tumors |
 Differential Diagnoses & Workup: Intestinal Stromal Tumors |
| Treatment & Medication: Intestinal Stromal Tumors |
| Follow-up: Intestinal Stromal Tumors |
| Multimedia: Intestinal Stromal Tumors |
| References |
| « Previous Page | Next Page » |
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Further Reading
Keywords
GIST, IST, GISTs, gastrointestinal stromal tumors, gastrointestinal mesenchymal tumors, GI mesenchymal tumors, gastrointestinal tumors, GI tumors, leiomyosarcoma, intestinal stromal tumors, interstitial cells of Cajal, GI tract, gastrointestinal malignancies, GI malignancies, gastric stromal tumors, gastrointestinal cancer, GI cancer, stomach cancer, stomach malignancy, stomach tumor, Carney triad, gastric stromal sarcoma, extra-adrenal paraganglioma, pulmonary chondroma, neurofibromatosis I
