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Gastrointestinal Stromal Tumors: a Pictorial Review
Danai Chourmouzi, Emmanouil Sinakos, Lavrentis Papalavrentios, Evaggelos Akriviadis, Antonios Drevelegas
Interbalcan Medical Center, Thessaloniki, Greece
Abstract
We describe the pertinent organ-specific clinical
manifestations of gastrointestinal stromal tumors (GISTs)
as well as the radiological appearances that allow optimal
depiction of pathology and diagnosis. Radiologic features
of GISTs vary depending on tumor size and organ of origin.
They most commonly have an exophytic growth pattern
and manifest as dominant masses outside the organ of
origin. Intramural and intraluminal masses are less common
radiologic manifestations. GISTs may contain areas of
hemorrhage, necrosis, or cyst formation that appear as focal
areas of low attenuation on computed tomographic images.
Most metastases of GISTs involve the liver and peritoneum
by hematogenous spread and peritoneal seeding. CT and
MRI are considered to be the imaging modality of choice
for the detection, staging, surgical planning and follow-up
of patients with GIST. A reduction in tumor size, extensive
cystic changes, and calcification in primary and metastatic
GISTs on CT and MRI indicate disease response to therapy.
Radiologists and clinicians must recognize the imaging
features of GISTs, detect, characterize the lesions and
evaluate the tumor response during specific treatment.
Keywords
Gastrointestinal stromal tumors – CT – MRI
Introduction
Gastrointestinal stromal tumors (GISTs) are the most
common mesenchymal neoplasms of the gastrointestinal
tract. The term GIST defines a unique group of mesenchymal
neoplasms that are distinct from true smooth muscle and
neural tumors [1].
Received: 04.03.2009Accepted: 16.03.2009
J Gastrointestin Liver Dis
September 2009 Vol.18 No 3, 379-383
Address for correspondence:
Danai Chourmouzi
Interbalcan Medical Center
Gymnasiou 20,
Thessaloniki, Greece
E-mail: [email protected]
GISTs display spindle cell or epithelioid morphologic
characteristics and specific immunohistochemical properties.
The most specific and important immunohistochemical
marker is the c-kit (CD117) protein, a tyrosine kinase
growth factor receptor. Many tumors previously diagnosed
as leiomyomas, leiomyoblastomas, or leiomyosarcomas
have been found to be positive for CD117 and are now
considered GISTs. This includes tumors involving most sites
in the gastrointestinal tract except the esophagus, where true
leiomyomas are more common than GISTs. All GISTs should
be considered as having malignant potential, although they
display varying degrees of aggressiveness [2, 3].
Although some families with hereditary GISTs have
been described, most cases are sporadic. GISTs occur in
10-20 per one million people. The true incidence might be
higher, as new laboratory methods are much more sensitive
in diagnosing GISTs [4].
GISTs can occur anywhere in the gastrointestinal (GI)
tract from the esophagus to the rectum, as well as the
omentum, mesentery, and retroperitoneum. Approximately
60–70% of GISTs occur in the stomach, and 25–35% arise in
the small intestine. Colon, rectum, appendix (together 5%)
and esophagus (2-3%) are rare sites. Less commonly, they
may arise in the mesentery, or omentum [1].
GISTs are usually solitary tumors. Most individuals are
over 50 years of age at the time of presentation, and GISTs
are rarely seen in patients younger than 40 years, although
there are several reports in the paediatric population [5].
Patients with neurofibromatosis type 1 (NF1) have an
increased prevalence of GISTs. Classically, patients with
NF1 have multiple small intestinal GISTs [6].
The clinical manifestations of GISTs depend on the
location and size of the tumors and are often nonspecific
[7, 8].
Imaging
The role of imaging includes the detection (subjects
with occult gastrointestinal bleeding, incidental recognition
etc), characterisation, analysis of relations between mass
and gastrointestinal wall, staging, prognostic assessment
380
(recognition of signs of malignancy and unfavourable
prognosis) and follow-up during specific treatment.
CT is considered to be the imaging modality of choice
for the detection, staging, surgical planning and follow-up
of patients with GIST. Because GISTs usually involve the
outer muscular layer, they have a propensity for exophytic
growth. Therefore, the most common appearance is that of
a mass arising from the wall of the gastrointestinal tract and
projecting into the abdominal cavity. Mucosal ulceration is
seen on the luminal surface of the tumor in up to 50% of
cases [9]. The majority of GISTs appear to be well-defined,
extraluminal or intramural masses with varying attenuation
on CT based on size. Small lesions, which are usually benign,
tend to be well-defined and relatively homogeneous (Fig.
1). Larger lesions normally show well-defined or ill-defined
margins, inhomogeneous density both on unenhanced and
on contrast-enhanced scans, with combined intraluminal/
extraluminal growth and a tendency to spread to surrounding
structures. Large tumors (>6cm) frequently show central
areas of necrosis or haemorrhage (Fig. 2). Central gas and
mural calcification are uncommon findings. Varying degrees
of necrosis may be frequently demonstrated within the mass.
A peripheral enhancement pattern correlated with central
hemorrhage, necrosis, or cyst formation and peripheral areas
of viable tumor have been reported [10, 11]. The masses
usually displace adjacent organs and vessels, but direct
invasion of the adjacent structures is sometimes seen with
advanced disease. Ascites is an uncommon feature [12]. The
above description applies to GISTs in all locations.
Chourmouzi et al
However, there are features of GISTs that may be unique
to location. Gastric GISTs commonly demonstrate extension
into the gastrohepatic ligament (Fig. 3), gastrosplenic
ligament, and lesser sac, and frequently, the bulk of the
tumor is seen in an extragastric location. Furthermore, the
cavities that develop from central necrosis or hemorrhage in
the larger tumors may communicate with the gastric lumen
(Fig. 4) [13].
GISTs may occur throughout the small intestine, usually
presented with signs and symptoms of obstruction or rarely
with hemorrhage . They may appear as intramural masses or
intraluminal polyps, and may show extension into adjacent
mesentery (Fig. 5). Small intestinal GISTs demonstrate
similar features of peripheral enhancement and central areas
of low attenuation. Encasement of adjacent small bowel,
colon, and bladder can be seen. Extension into the adjacent
small bowel mesentery and encasement of noncontiguous
segments of small intestine, colon, bladder, ureter, and
abdominal wall may occur. The differential diagnosis
for small intestinal GISTs includes adenocarcinoma and
lymphoma. Adenocarcinoma typically manifests as an
annular lesion in the proximal small intestine; thus, its
appearance usually does not overlap with that of GISTs.
Lymphoma, however, has many features similar to those
of GISTs. The presence of associated lymphadenopathy,
however, would favor the diagnosis of lymphoma [14].
Anorectal GISTs most commonly present as welldefined, eccentric mural masses that expand the rectal wall
and may contain mucosal ulceration. The mass spreads via
extension into the ischiorectal fossa, prostate, or vagina. As
in GISTs at other locations, central areas of hemorrhage can
be seen [15].
Colonic GISTs are described as transmural tumors that
involve the intraluminal and extraserosal surfaces of the
colon. Other features include cystic change, hemorrhage,
necrosis, or calcification. Colonic GISTs have been seen to
exhibit circumferential growth and secondary dilatation of
the affected colonic segment.
Fig 1. Gastric GISTs. a) CT of the abdomen in a 58 year old woman
complaining of pelvic pain shows an incidental homogeneous
exophytic ovoid mass in the gastric fundus (arrow). b) Gastric
GIST in a 64-year-old man who presented for an annual checkup with mild epigastric discomfort. CT image shows an ovoid,
homogeneous, mural-based mass along the fundus of the stomach
with intraluminal and exophytic component (arrows).
Fig 2. Small intestine GIST. Axial contrast-enhanced CT scans
(a, b) of mid abdomen show a large inhomogeneous mass arising
from small bowel with large exophytic component and necrotic
hypodense areas.
Fig 3. GIST arising from the lesser curvature of the
stomach in a 60 year old man that was incidentally
discovered. CT scan shows a homogeneous muralbased extraluminal mass along the lesser curvature.
The mass extends into the gastrohepatic ligament
(arrows).
Gastrointestinal stromal tumors
381
Fig 4. Gastric GIST. Contrast-enhanced CT scan (a,b), of a 66-year-old man with abdominal pain
shows a cavitary mass in the stomach that contains air and oral contrast material (arrow). The
oral contrast material within the mass is due to a fistula to the gastric lumen. c) The cut surface
of the resected specimen shows the mass with the fistula (arrow).
Fig 5. Small intestinal GIST in a 60-year-old woman with acute
abdominal pain. a) CT scan shows dilated segments of the small
intestine and the well-circumscribed intraluminal mass in the right
side of the abdomen b). In the above level intussusception of the
ileus is seen (arrow).
Fig 6. Mesenteric GIST in a 83-year-old man presenting with weight
loss. a) Axial CT image shows a mesenteric heterogeneous mass. b)
cystic splenic metastasis was seen on post-contrast CT scan.
GISTs may originate from the mesentery and secondarily
involve the small intestine. The presence of hemorrhage,
necrosis, and cystic change in these tumors results in the
appearance of a complex mass on cross-sectional imaging.
The imaging appearance of mesenteric and omental
GISTs is indistinguishable from that of other sarcomas that
may arise in these locations [16] (Fig 6).
Signs of high-grade GIST include liver metastasis, GI
wall infiltration, large volume, irregular surface, ill-defined
margins, inhomogeneous enhancement and peritoneal spread
(Figs. 6, 7). No definite correlation between radiologic
appearance and malignant potential has been established with
regard to the degree of necrosis, hemorrhage, cyst formation,
or contrast material enhancement on CT images.
On MR imaging (MRI) solid portions of tumours
Fig 7. Advanced GIST with multiple peritoneal
implants in the surface of the liver. Contrastenhanced CT scan through the upper abdomen shows
a large hypodense mass along the great curvature of
the stomach (arrows) and hypodense liver implants
(arrows).
typically show low signal intensity on T1-weighted images,
intermediate to high signal intensity on T2-weighted images,
and enhancement after administration of gadolinium (Figs.
8, 9). The marked high signal seen on T2-weighted MRI
should be considered as a feature strongly indicating
diagnosis of GIST [17]. The multiplanar capability of MRI
may be helpful in determining the organ of origin in large
tumours (Fig. 10).
Nearly 50% of patients with GISTs present with
metastasis. Most metastases of GISTs involve the liver
and peritoneum by hematogeneous spread and peritoneal
seeding, respectively. Less commonly, metastases are found
in the soft tissue, lungs, and pleura. Unlike gastrointestinal
adenocarcinomas, GISTs metastasizing to the lymph nodes
are extremely rare.
The CT characteristics of metastatic lesions of GISTs are
similar to those of primary tumors: enhancing masses that
can be heterogeneous because of necrosis, hemorrhage, or
cystic degeneration [18].
The primary treatment goal for localized primary GIST is
complete resection, without the need for lymphadenectomy
or wide resection margins. Thus, gastric wedge resections
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Chourmouzi et al
Fig 8. GIST of the stomach in a 66-year-old woman.
Axial T2-weighted MR image shows an extraluminal
mass (arrow) arising from the greater curvature of
the stomach. The mass shows high signal intensity
(arrows).
and segmental resections of the small bowel are the most
common surgical procedures. Until recently, the only therapy
that has proved effective for GISTs has been surgical
resection. In 2001, Joensuu et al [19] published a case report
about a nonresectable, widely metastatic GIST that showed a
very dramatic response to a tyrosine kinase inhibitor, STI571
(Gleevec, Novartis). This drug is a molecular targeted
therapy, and acts on the c-kit growth factor receptor, which
is the most important diagnostic marker of GISTs.
In general practice, contrast-enhanced CT is routinely
used to monitor tumor response. The degree and pattern
of enhancement observed on CT scans are useful for
identifying post treatment changes. On contrast-enhanced
CT, a response to imatinib is characterized by rapid transition
from a heterogeneously hyperattenuating pattern to a
homogeneously hypoattenuating pattern with resolution of
the enhancing tumor nodules and a decrease in tumor vessels.
The density of hepatic metastases decreases after treatment
to approximately 20–25 H, which is near to, but greater
than that for a true cyst (<15 H). This Hounsfield unit range
Fig 10. Gastric GIST. Axial post contrast 3D fat-suppressed VIBE
image shows a low signal peripheral enhancing mass in the mid
abdomen. On the coronal (b) image the lesser gastric curvature as
site of origin is better depicted. Note the low signal metastatic liver
focus as well (arrow).
Fig 11. Mesenteric GIST. (a,b) Pre-treatment CT scans show a large
lobulated mesenteric mass with low attenuated areas (c) Follow-up
CT scans 9 months after treatment, show that the mass has become
homogeneous and hypoattenuating, with significant decreases in
the attenuation and size of the tumor (c) 16 months after treatment
the mass further decreases with coarse calcification. Such findings
typify a good response to imatinib.
Fig 9. Gastric GIST. (a) Gastroscopy image shows a submucosal mass (b) Coronal T2W image
shows an exophytic gastric mass with intemediate signal intensity (c) On STIR axial image the
mass shows high signal intesnity (d) VIBE image. The lesion shows low signal intensity. After
contrast the mass shows minimal peripheral enhancement in arterial (e) and intense enhancement
in portal phase (f) (arrows).
Gastrointestinal stromal tumors
may be helpful in differentiating true cysts from metastases
after treatment with Gleevec (Fig. 11). Similarly on MRI
the metastatic lesions after treatment become bright on T2
images and remain unenhanced on post contrast images
(Fig. 12).
Fig 12. Hepatic metastasis 4 years after radical resection small
bowel GIST. a) Axial T2W image shows a high signal target like
metastasis in the right liver lobe. (b) after the administration of
contrast medium a ring like peripheral enhancement is seen. (c) 6
weeks after therapy the lesion became cystic with homogeneous
high signal intensity on T2W image. (d) on post contrast image the
lesion remain unenhanced.
In conclusion, a reduction in tumor size, extensive
cystic changes, and calcification in primary and metastatic
GISTs on CT or MRI indicate a disease response. The early
detection of focal solid or new solid lesions after maximal
dose of imatinib mesylate suggests disease progression and
might be helpful in early intervention such as surgery or new
tyrosine kinase inhibitors [20].
Conflicts of interest
None to declare.
References
1. Miettinen M, Lasota J. Gastrointestinal stromal tumors: definition,
clinical, histological, immunohistochemical, and molecular genetic
features and differential diagnosis. Virchows Arch 2001; 438:
1–12.
2. Du CY, Shi YQ, Zhou Y, Fu H, Zhao G. The analysis of status and
clinical implication of KIT and PDGFRA mutations in gastrointestinal
383
stromal tumor (GIST). J Surg Oncol 2008; 98: 175-178.
3. Lasota J, Miettinen M. Clinical significance of oncogenic KIT
and PDGFRA mutations in gastrointestinal stromal tumours.
Histopathology 2008; 53: 245-266.
4. Blanke C, Eisenberg BL, Heinrich M. Epidemiology of GIST. Am
J Gastroenterol 2005; 100: 2366.
5. Egloff A, Lee EY, Dillon JE. Gastrointestinal stromal tumor (GIST) of
stomach in a pediatric patient. Pediatr Radiol 2005; 35: 728-729.
6. Fuller CE, Williams GT. Gastrointestinal manifestations of type 1
neurofibromatosis (von Recklinghausen’s disease). Histopathology
1991; 19: 1–11.
7. Filippou DK, Pashalidis N, Skandalakis P, Rizos S. Malignant
gastrointestinal stromal tumor of the ampulla of Vater presenting
with obstructive jaundice. J Postgrad Med 2006; 52: 204-206.
8. Towu E, Stanton M. Gastrointestinal stromal tumour presenting with
severe bleeding: a review of the molecular biology. Pediatr Surg Int
2006; 22: 462-464.
9. Suster S. Gastrointestinal stromal tumors. Semin Diagn Pathol 1996;
13: 297–313.
10. Levy AD, Remotti HE, Thompson WM, Sobin LH, Miettinen M.
Gastrointestinal stromal tumors: radiologic features with pathologic
correlation. Radiographics 2003; 23: 283-304.
11. Sharp RM, Ansel HJ, Keel SB. Best cases from the AFIP:
gastrointestinal stromal tumor. Armed Forces Institute of Pathology.
Radiographics 2001; 21: 1557–1560.
12. Sandrasegaran K, Rajesh A, Rushing DA, Rydberg J, Akisik FM,
Henley JD.Gastrointestinal stromal tumors: CT and MRI findings.
Eur Radiol 2005; 15: 1407-1414.
13. Hasegawa S, Semelka RC, Noone TC, et al. Gastric stromal sarcomas:
correlation of MR imaging and histopathologic findings in nine
patients. Radiology 1998; 208: 591–595.
15. Buckley JA, Fishman EK. CT evaluation of small bowel neoplasms:
spectrum of disease. Radiographics 1998; 18: 379- 392.
16. Miettinen M, Monihan JM, Sarlomo-Rikala M, et al. Gastrointestinal
stromal tumors/smooth muscle tumors (GISTs) primary in the
omentum and mesentery: clinicopathologic and immunohistochemical
study of 26 cases. Am J Surg Pathol 1999; 23: 1109–1118.
17. Caramella T, Schmidt S, Chevallier P, at al. MR features of
gastrointestinal stromal tumors. Clin Imaging 2005; 29: 251-254.
18. Hong X, Choi H, Loyer EM, Benjamin RS, Trent JC, Charnsangavej
C. Gastrointestinal stromal tumor: role of CT in diagnosis and in
response evaluation and surveillance after treatment with imatinib.
Radiographics 2006; 26: 481-495.
19. Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of tyrosine
kinase inhibitor STI571 in a patient with metastatic gastrointestinal
stromal tumor. N Engl J Med 2001; 344: 1052–1066.
20. Choi H, Charnsangavej C, de Castro Faria S, et al. CT evaluation
of the response of gastrointestinal stromal tumors after imatinib
mesylate treatment: a quantitative analysis correlated with FDG PET
findings. Am J Roentgenol 2004; 183: 1619-1628.