eMedicine Specialties > Radiology > Gastrointestinal

Gastrointestinal Stromal Tumors - Leiomyoma/Leiomyosarcoma

Vu H Nguyen, MD, Staff Physician, Department of Radiology, University of Wisconsin Hospitals and Clinics
Andrew Taylor, MD, Professor, Department of Radiology, University of Wisconsin Hospitals and Clinics

Updated: Aug 5, 2008

Introduction

Background

Gastrointestinal stromal tumors (GISTs) are a subset of GI mesenchymal tumors of varying differentiation. Previously, these tumors were classified as GI leiomyomas, leiomyosarcomas, leiomyoblastomas, or schwannomas, on the basis of histologic findings and the fact that these tumors apparently originate in the muscularis propria layer of the intestinal wall. With the advent of immunohistochemical staining techniques and ultrastructural evaluation, GISTs now are recognized as a distinct group of mesenchymal tumors. In the present classification, GISTs account for approximately 80% of GI mesenchymal tumors.¹

Most tumors referred to as leiomyomas and leiomyosarcomas in the older medical literature are actually GISTs.² Only with tumors in the esophagus does the term leiomyoma remain accurate. Leiomyomas are the most common mesenchymal tumors in the esophagus; they rarely occur in the stomach and small bowel. In contrast, GISTs are rare in the esophagus, and they are more common in the stomach and small bowel.

The literature about GISTs remains confusing because tumor classification and terminology are being continually refined. Furthermore, the exact definition of GISTs varies among authors. Some use the term to describe any GI submucosal mesenchymal tumor that is not myogenic (eg, leiomyosarcoma) or neurogenic (eg, schwannoma) in origin. Other authors are more restrictive and use the term when specifically referring to GI mesenchymal tumors that express the CD117 and/or CD34 antigen. This review includes material representing both points of view.³

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Pathophysiology

Grossly, gastrointestinal stromal tumors (GISTs)are well-demarcated spherical masses that appear to arise from the muscularis propria layer of the GI wall. Intramural in origin, they often project exophytically and/or intraluminally, and they may have overlying mucosal ulceration. Larger GISTs nearly always outgrow their vascular supply, leading to extensive areas of necrosis and hemorrhage (see Images 1-2).^2,4

The diameter of GISTs, as a whole, can range from a few millimeters to more than 30 cm. Although larger tumors have a higher rate of malignancy, size does not predict benignity, and small GISTs have been known to behave in a malignant fashion.^4,5 Malignancy is characterized by local invasion and metastases, particularly to the liver.

Cytologically, GISTs can be classified into 2 broad categories: spindle cell GISTs and epithelioid GISTs. Spindle cell GISTs are characterized by nuclear palisading or prominent perinuclear vacuolization pattern. Epithelioid GISTs may have either a solid pattern or a myxoid pattern, with a possible compartmental pattern. Although GISTs may differentiate along either or both cell types, some show no significant differentiation at all.^2,4,6

The number of mitotic figures present may be used to histologically grade GISTs. Unfortunately, no standard exists for their classification. In general, GISTs with less than 1 mitotic figure per 50 high-powered fields (HPFs) are correlated with benign behavior. A finding of 1-5 mitoses per 10 HPFs suggests potential malignancy. A finding of more than 5 per 10 HPFs indicates malignancy. A finding of more than 10 per 10 HPFs denotes high-grade malignancy.^2,4,7

Although radiologic or histologic results may suggest GISTs, the diagnosis must be made immunochemically. Independent of location, most GISTs express the CD34 antigen (70-78%) and the CD117 (72-94%) antigen. The CD34 protein is a hematopoietic progenitor cell antigen that occurs in a variety of mesenchymal tumors. CD117 also is known as the c-kit protein; it is a membrane receptor with a tyrosine kinase component. Mutations in the CD117 gene have been linked to malignant behavior in GISTs.^2,4,8,9,10

Some authors specifically use the term GIST to refer only to those mesenchymal tumors that express CD117, whereas others believe that the diagnosis may be made in the absence of CD117 positivity on the basis of clinical and morphologic features.^1,2,11 Some GISTS without the KIT mutation have been found to express a mutation in another tyrosine kinase receptor gene, the PDGFRa gene. This gene encodes the platelet-derived growth factor receptor (alpha receptors) tyrosine kinase protein.^12,13

Interstitial cells of Cajal are GI pacemaker cells that regulate intestinal motility and peristalsis. A relationship between GISTs and Cajal cells has been proposed, because these are the only 2 intestinal entities that express both CD34 and CD117. Whether GISTs are Cajal cell tumors or whether they share a common progenitor cell is unknown.^1,2,14

Other markers that have been used in the evaluation of GISTs include desmin, actin, and S100. About 20-30% of GISTs express smooth muscle actin, only 5-10% express desmin, and as many as 10% express S100.² In contrast, true leiomyomas and leiomyosarcomas typically express desmin and actin but not CD34 and CD117, although some leiomyosarcomas may contain isolated CD117 cells. This finding is in contrast to the generally global presence of CD117 in GISTs.² Schwannomas typically express S100 but not CD34 and CD117.^2,9,14,15

About 10-30% of GISTs have malignant behavior.^1,2 A benign GIST cannot be conclusively diagnosed, because even small, histologically benign-appearing tumors may later demonstrate clinically aggressive behavior. Factors that are correlated with an improved prognosis include a gastric location, a diameter of less than 2 cm, a low mitotic index, and an absence of tumor spillage with complete gross resection.

Major negative prognostic factors include large size (>5 cm), high mitotic index, and grossly positive resection margins. Other factors with poor prognosis include tumor rupture, distal location, high cellularity, tumor necrosis, the presence of metastases or invasion, and mutation in the c-kit gene.^1,2,6,10 Findings from 2 studies show that with microscopic resection, margins are not correlated with improved outcome.^6,7 Given the potential malignant behavior of benign-appearing GISTs, at least 1 group believes that all GISTs should be classified as malignant and then graded on a low-to-high scale rather than classified on a benign-versus-malignant basis.⁷

GISTs rarely spread to regional lymph nodes (<10%). Rather, malignancy is manifested by local invasion; distant metastases most commonly involve liver (50-65%) and peritoneum (21-43%) (see Image 3). Only 10% of metastatic lesions occur in the lungs or bones.^{2,5,6,7,10,16}

Frequency

United States

Gastrointestinal stromal tumors (GISTs) are rare; they constitute less than 3% of all GI malignant neoplasias.^4,7,17 They represent only 20% of small-bowel malignant neoplasms (excluding lymphoma); 1-2% of gastric malignancies; and less than 1% of malignancies involving the esophagus, colon, and rectum.^1,4,5,6,16 On presentation, 41-47% of malignant GISTs are metastatic.^2,6,16,7

Mortality/Morbidity

Without taking presentation into account, the disease-specific survival rates of patients with malignant gastrointestinal stromal tumors (GISTs) were 69% at 1 year, 38-44% at 3 years, and 29-35% at 5 years. Benign GISTs were not included in the findings from 2 surgical studies cited. Median disease-specific survival was 60 months with primary disease, 19 months with metastatic disease, and 12 months with local recurrence.^6,7

In patients who had malignant primary disease and who underwent complete gross resection of the tumor, 40% had recurrence; in 1 study, 91% of the patients died from the disease during the course of the study. The disease-specific survival rate in this group of patients was 88% at 1 year, 54-65% at 3 years, and 42-54% at 5 years. Median survival was 66 months in those who underwent complete gross resection of the primary disease and only 22 months in patients with incomplete or nonresectable primary tumors. Recurrence is common; the rate has been reported to be as high as 90% at long-term follow-up.^4,6,7

Race

No racial predilection exists for gastrointestinal stromal tumors (GISTs).

Sex

The incidence of gastrointestinal stromal tumors (GISTs) is approximately equal in males and females. Some studies show a slight preponderance in men.^2,4,5

Age

The unimodal peak incidence of gastrointestinal stromal tumors occurs in persons aged 40-70 years, but the distribution of GISTs is broad. Very rarely, pediatric cases have been reported.^2,5,4

Anatomy

About 50-70% of gastrointestinal stromal tumors (GISTs) occur in the stomach; 33%, in the small bowel; 5-15%, in the rectocolon; and only 1-5%, in the esophagus.^{1,4,5,6,11,16} GISTs are multicentric in fewer than 5% of cases (see Images 5-6).

Presentation

At presentation, the clinical spectrum of gastrointestinal stromal tumors is wide. Benign, asymptomatic GISTs may be detected incidentally; large, malignant tumors frequently cause the patient to seek medical attention.²

When GISTs are symptomatic, the symptoms usually occur as a result of the size of the tumor or because the tumor has a tendency to ulcerate and bleed. The most common presenting signs and symptoms include abdominal pain; GI bleeding, manifested by hematemesis or melena; and a palpable mass. Although these tumors rarely cause obstruction, they become perforated in as many as 20% of cases. The rare esophageal GIST most often causes symptoms of dysphagia, as a result of obstruction, with subsequent weight loss.^{1,2,4,5,7,8,18}

Limitations of Techniques

The aim of radiologic examination is to locate gastrointestinal stromal lesions, evaluate local invasion, and detect distant metastases. The radiographic characteristics of GISTs mirror the gross appearance of these tumors. Small GISTs appear as small, well-circumscribed intramural masses, possibly with overlying ulceration. Larger malignant GISTs appear as complex masses with areas of necrosis, which occur as a result of the tumor's outgrowing its blood supply.

Unfortunately, radiologic findings are nonspecific and may represent several entities. Also, the distinction between benign and malignant GISTs cannot be made with radiologic examinations unless metastatic disease or tumor invasion of adjacent structures is depicted. The definitive diagnosis of GIST is made immunohistochemically. However, the diagnosis may be suggested in the case of a complex bowel mass with liver metastases in the absence of lymphadenopathy.¹⁹

Differential Diagnoses

Carcinoid, Gastrointestinal
Colon, Adenocarcinoma
Gastric Carcinoma
Liposarcoma, Soft Tissue

Other Problems to Be Considered

Angiosarcoma
Inflammatory fibroid polyp
Inflammatory myofibroblastic tumor (pseudotumor, fibrosarcoma)
Intra-abdominal fibromatosis
Kaposi sarcoma
Lipoma
Lymphoma, abdominal
Melanoma, metastatic
Schwannoma, GI

Radiography

Findings

Plain radiographs usually offer little in the evaluation of gastrointestinal stromal tumors (GISTs). In the chest, esophageal GISTs may appear as a soft tissue mass in the lower two thirds of the mediastinum. In the abdomen, the soft tissue mass may cause deformation of the gastric air shadow, or it may displace loops of bowel. Abdominal films may depict an obstructive bowel pattern. If they are necrotic lesions, collections of air may be visualized within the tumor.²⁰

Regardless of the location of GISTs, barium-enhanced images demonstrate predominantly intramural masses with potential exophytic components. The tumor margins usually are smooth, but with ulceration, some surface irregularity is present. As with other intramural masses, the tumor borders form right or obtuse angles with the adjacent visceral wall. En face, the intraluminal surfaces often have well-defined margins (see Images 7-10).

Because the tumors are intramural but extramucosal, the overlying mucosa may be intact. With tumors of the stomach, areae gastricae is preserved over the tumor mass. However, overlying mucosal ulcerations are often present; they are more common in malignant GISTs. These ulcerations fill with barium, causing a bull's-eye or target-lesion appearance (see Image 11).

If necrosis and cavitation are present, barium may fill the inner parts of the tumor mass (see Images 12-13).^4,5,18,20,21 At times, the mass is entirely exophytic and, thus, is not appreciated during contrast-enhanced examination. Barium images outline the intraluminal portion of this tumor; frequently, a substantial exophytic extension is present (see Images 14-15).

Degree of Confidence

One group reported that double-contrast images show abnormalities in 80% of cases of gastrointestinal stromal tumors (GISTs).⁴

Computed Tomography

Findings

CT for gastrointestinal stromal tumors (GISTs) should be performed with both oral and intravenous contrast materials. CT is ideal in defining the endoluminal and exophytic extent of tumor. Smaller gastrointestinal stromal tumors appear as smooth, sharply defined intramural masses with homogeneous attenuation (see Image 9).

With contrast enhancement, the tumor may appear to have a rim, or it may be uniform in appearance (see Image 15). Occasionally, dense focal calcifications are present. Larger GISTs with necrosis appear as heterogeneous masses with enhancing borders of variable thickness and irregular central areas of fluid, air, or oral contrast attenuation that reflect necrosis (see Image 4, Image 13). Overlying mucosal ulcerations may be present, and the tumor may extend into nearby structures.

CT is sensitive for the detection of metastatic liver, peritoneal, lung, and bone lesions. The diagnosis of GIST may be suggested by the presence of a large, complex, intestinal mass with liver lesions but without significant lymphadenopathy. Liver lesions can be hypervascular, or they may appear as cystic multilocular lesions with fluid-fluid levels (see Image 21).^{2,5,8,18,20,22}

Degree of Confidence

CT scanning has good sensitivity for the detection of GISTs; abnormalities may be seen in 87% of cases.⁴

Magnetic Resonance Imaging

Findings

Among imaging studies, MRI has the best tissue contrast, which aids in the identification of masses within the GI tract. Furthermore, the ability to image in multiple planes facilitates localization and diagnosis. Intravenously administered contrast material is needed to evaluate lesion vascularity.

Gastrointestinal stromal tumors (GISTs) appear as sharply delineated, heterogeneous masses with cystic and necrotic areas. The masses tend to be isointense relative to skeletal muscle on T1-weighted images and hyperintense on T2-weighted images. Signal-intensity voids are present if gas is present within areas of necrotic tumor.^18,20,23

Ultrasonography

Findings

Ultrasonography is ideal for guided-needle biopsy of known lesions, if such a procedure is indicated. With immunohistochemical staining methods, the diagnosis may be made before surgery.²⁴ However, aspiration (eg, fine-needle aspiration) and biopsy should be used selectively because of the risk of tumor seeding or peritoneal spillage.^4,25 Both are associated with a worse prognosis.

On sonograms, larger gastrointestinal stromal tumors (GISTs) appear as complex masses with cystic and solid components, which are consistent with their tendency to undergo necrosis.^20,23

Endoscopic ultrasonography may be valuable in the evaluation of GISTs. The tumors appear as hypoechoic masses that are contiguous with the fourth hypoechoic layer of the GI wall, which corresponds to the muscularis propria. Characteristics associated with malignancy include tumor size greater than 4 cm, an irregular extraluminal border, echogenic foci, and the presence of cystic spaces.⁴

Degree of Confidence

Ultrasonography is only moderately sensitive for the detection and evaluation of gastrointestinal stromal tumors. Bowel gas and acoustic shadowing obscure portions of the bowel and mesentery.

Angiography

Findings

On angiography, gastrointestinal stromal tumors (GISTs) appear as relatively well-circumscribed, hypervascular lesions with central avascularity. They have large feeding arteries and draining veins, and they show intense tumor staining (see Images 16-20).⁸

Intervention

Previously, the only proven treatment for gastrointestinal stromal tumors (GISTs) was surgical resection.^5,6 Radiation therapy and chemotherapy have been ineffective.

Imatinib mesylate (Gleevec; Novartis) initially helps control disease in 80% or more of patients. Imatinib mesylate is an inhibitor of tyrosine kinases, including the KIT receptor and the PDGRF receptors and their oncogenic activated forms.¹² Imatinib mesylate has proved to be effective in early- and late-stage disease. Posttreatment, liver lesions become better defined and cystlike (see Image 4). In one study, an objective response was observed in 50-60% of cases; in 10-15% of cases, the disease progressed despite therapy.²⁵ In other patients, resistance developed following initial responses. Factors thought to be involved include gene amplification and the presence of additional mutations, which may lend GIST tumors an inherent resistance.^{26,27,28,29,30}

Multimedia

Media file 1: Small-bowel gastrointestinal stromal tumor with a diffusely thickened bowel wall.

Media file 2: Gastrointestinal stromal tumor. Image obtained in the same patient as in Image 1. A more caudal portion of the tumor has areas of necrosis (arrows), with air present within the necrotic cavity that communicates with the lumen of the small bowel.

Media file 3: Small-bowel gastrointestinal stromal tumor with multiple liver metastases (arrows).

Media file 4: Gastrointestinal stromal tumor. Image obtained in the same patient as in Image 3 after imatinib mesylate (Gleevec) administration. Note the decreased size of the liver metastases.

Media file 5: Multifocal gastrointestinal stromal tumors. Barium examination reveals a smooth mass that causes narrowing in the second portion of the duodenum (arrows).

Media file 6: Gastrointestinal stromal tumor (GIST). CT scan obtained in the same patient as in Image 5 shows a focal segment of diffusely thickened ileum, which is another GIST.

Media file 7: Gastric gastrointestinal stromal tumor in a 49-year-old woman. The mass was found incidentally during an upper GI workup for peptic disease. The smooth appearance suggests a submucosal process.

Media file 8: Gastrointestinal stromal tumor (GIST). Image obtained 1 year later in the patient in Image 7. The mass has increased in size. A GIST was found at surgery.

Media file 9: Gastrointestinal stromal tumor (GIST). CT scan obtained in the patient in Images 7-8 shows the same GIST. It appears as an intramural mass with both exophytic and endophytic components.

Media file 10: Gastric gastrointestinal stromal tumor (GIST) en face. Upper GI image obtained during the single contrast enhancement portion shows an incidentally found mass. The smooth borders suggest a submucosal process. At surgery, a GIST was found.

Media file 11: Gastrointestinal stromal tumor with central bull's eye appearance, which is compatible with contrast material collection in an ulceration.

Media file 12: Gastric gastrointestinal stromal tumor with huge exophytic component, which has become ulcerated. Barium collects in the exophytic ulcer crater (arrows).

Media file 13: Gastrointestinal stromal tumor (GIST). CT scan obtained in the patient in Image 12 demonstrates the GIST with large exophytic ulceration (arrows).

Media file 14: Proximal jejunal gastrointestinal stromal tumor that is completely exophytic and not visible at small-bowel barium examination.

Media file 15: Gastrointestinal stromal tumor (GIST). Contrast-enhanced CT obtained in the same patient as in Image 14 demonstrates a peripherally enhancing mass immediately adjacent to the pancreas that was thought to be a pancreatic neoplasm. However, at surgery, this proved to be a proximal exophytic jejunal GIST.

Media file 16: Gastrointestinal stromal tumor. A 62-year-old women presented with 2 episodes of massive GI bleeding. Nuclear medicine GI bleed scanning demonstrates increased tracer activity in the mid abdomen (arrows) consistent with a small bowel active bleed. Courtesy of Dr Jon Wood and Dr John McDermott, University of Wisconsin Hospitals and Clinics.

Media file 17: Gastrointestinal stromal tumor (GIST). Patient in Image 16 then underwent angiography, which demonstrates a mass (white arrows) in the same location as the small-bowel bleed. The blood supply is from the superior mesenteric artery (red arrow). Minimal mass effect on the bladder is noted (yellow arrows). Findings are consistent with a small bowel mass, which stained positive for CD117; this result is consistent with a GIST.

Media file 18: Gastrointestinal stromal tumor. Selective masked injection in the superior mesenteric artery (red arrow) demonstrates a large arterial feeder with tumor staining (white arrows).

Media file 19: Gastrointestinal stromal tumor. Delayed images demonstrate large draining vein, which empties into the superior mesenteric vein (red arrow).

Media file 20: Gastrointestinal stromal tumor. Enteroclysis results were surprisingly normal. No abnormalities are seen, and no significant mass effect suggests the presence of the mass.

Media file 21: Gastrointestinal stromal tumor (GIST). CT demonstrates a complex mass originating from the small bowel with characteristics of a GIST.

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Keywords

gastrointestinal stromal tumors, gastrointestinal neoplasms, GIST, GI stromal tumors, GI tumors, gastrointestinal tumors, leiomyoma, leiomyosarcoma, gastrointestinal sarcoma, gastrointestinal mesenchymal tumor, GISTs, leiomyoblastoma, schwannoma, CD34, CD117, c-kit, benign tumors, stomach cancer

Contributor Information and Disclosures

Author

Vu H Nguyen, MD, Staff Physician, Department of Radiology, University of Wisconsin Hospitals and Clinics
Vu H Nguyen, MD is a member of the following medical societies: American College of Radiology and Radiological Society of North America
Disclosure: Nothing to disclose.

Coauthor(s)

Andrew Taylor, MD, Professor, Department of Radiology, University of Wisconsin Hospitals and Clinics
Andrew Taylor, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

Udo P Schmiedl, MD, PhD, Clinical Professor, Department of Radiology, University of Washington; Consulting Staff, Swedish Medical Center, University of Washington Medical Center, Seattle Radiologists
Udo P Schmiedl, MD, PhD is a member of the following medical societies: American College of Radiology and Radiological Society of North America
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

Eugene C Lin, MD, Clinical Assistant Professor of Radiology, University of Washington Medical School
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, and Society of Nuclear Medicine
Disclosure: Nothing to disclose.

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