Gastrointestinal stromal tumors (GISTs) are relatively rare tumors of the gastrointestinal tract and are known for their response to imatinib mesylate. The authors’ limited experience with GISTs and a review of published data suggests that positron emission tomography imaging with 18F-fluorodeoxyglucose along with anatomic imaging is better than CT alone in the diagnosis, staging, restaging, and measurement of therapeutic response of these neoplasms.
is a Senior Nuclear Medicine Resident and
is a Professor of Radiology and the Director, of the Division of
Nuclear Medicine and PET Center at the University of Missouri
Heath Care, Columbia, MO.
Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal
tumors of the gastrointestinal tract. These tumors are more common
in older individuals but can occur at any age. Gastrointestinal
stromal tumors are most common in the stomach but may occur
anywhere in the gastrointestinal tract, omentum, or mesentery.
Clinical presentation usually depends on tumor size. Small tumors
are generally asymptomatic and are discovered incidentally at
surgery. Large tumors usually produce symptoms, such as
gastrointestinal bleeding, abdominal pain, abdominal mass, nausea,
vomiting, and bowel obstruction.
Computed tomography (CT) is commonly employed for localization
and staging. The typical CT findings are the presence of a large
well-circumscribed mass arising from the stomach or small
intestines that is usually extraluminal. The mass may have a
heterogeneously enhancing soft-tissue rim surrounding a necrotic
Positron emission tomography (PET) using 18F-fluorodeoxyglucose
(FDG) is a promising new imaging modality for GIST. A PET scan can
show increased glucose metabolism, which appears to correlate with
In this report, we describe 4 cases of GIST in which FDG-PET played
an important role in the management of patients with these tumors.
The PET scans were useful in initial staging and in restaging the
tumors and in predicting response to therapy.
A 52-year-old man was diagnosed with leiomyosarcoma of the small
bowel in 1988. He was initially treated with partial small-bowel
resection and did not receive any adjuvant therapy at that time. On
a follow-up CT 5 years later, he was found to have tumor recurrence
in the liver. The patient had a partial hepatectomy with excellent
results. Nine years after that, he presented with abdominal
distension and pain in the right upper abdomen. A CT scan of the
abdomen revealed a large (10 × 14 cm) heterogeneous mass between
the portal vein and inferior vena cava, above the level of the left
kidney and posterior to the duodenum and the head of the pancreas.
Radio-frequency ablation and resection was attempted, but extensive
spread of the tumor did not permit complete resection. On
immunohistochemistry examination, the tumor was found to have CD117
antigen, which is an established hallmark of GIST. Soon afterward
the patient was enrolled in a clinical trial and received imatinib
mesylate (Gleevec, Novartis Pharmaceuticals Corp., East Hanover,
NJ), a tyrosine kinase receptor inhibitor.
The patient did well, with marked improvement of his symptoms
for 3 years until he presented with recurrence on the present
admission. A CT scan of the ab-domen and pelvis exhibited a 10- ×
7-cm right liver lobe mass and a 12-× 6-cm subhepatic mass (Figure
1). A necrotic pelvic lymph node measuring 3 × 3 cm was also noted
on CT (Figure 1). A PET scan was done using 21 mCi of 18F- FDG and
a dedicated scanner equipped with lutetium oxyorthosilicate (LSO)
crystal (Siemens ACCEL, Siemens Medical Solutions, Malvern, PA).
Whole-body images were acquired approximately 1 hour after
injection. The PET scan showed markedly increased uptake in the
liver and the subhepatic masses (Figure 1). There was no uptake in
the pelvic region, excluding a pelvic lesion. The PET helped in
accurate re-staging by indicating the malignant nature of the
hepatic and subhepatic masses and excluding pelvic spread.
A 42-year-old woman presented with dysphagia in October 2002. An
upper gastrointestinal (GI) endoscopy revealed a benign-appearing
stricture in the lower esophagus and an 8-cm tumor in the gastric
wall. A partial gastrectomy was performed, and CD117 was identified
in the resected mass. A postoperative CT scan was negative for
residual disease. Imaging with FDG-PET was performed using the
procedure described above for staging following surgery. Absence of
uptake in the abdomen confirmed successful resection of the gastric
mass and proved the benign nature of the esophageal stricture. A
small focus of increased uptake was noted in the lower neck (Figure
2). Ultrasound of the neck showed a 1.3-× 1.4-cm nodule in the
right thyroid lobe correlating with the PET scan finding (Figure
2). Biopsy revealed papillary thyroid carcinoma. The patient
underwent a total thyroidectomy and thyroid ablation therapy with
A 69-year-old man with a history of prostatectomy and radiation
therapy for prostate cancer presented with a new onset of
hematuria. A CT scan showed a heterogeneous mesenteric density
measuring 10 × 17 × 7 cm, as well as an additional well-defined
soft-tissue density measuring
7.0 × 4.0 × 4.0 cm in the same area. On exploratory laparotomy,
only part of the mass could be resected. On pathologic examination,
most of the mass was found to be sclerosing mesenteritis with a
small portion (1 cm) representing CD117-positive GIST. A PET scan
performed postoperatively at an outside hospital was positive for
residual disease. The patient underwent Gleevec therapy with an
excellent clinical response.
Six months later, a follow-up CT exhibited a residual tumor mass
measuring approximately 5.6 × 4.0 cm that remained essentially
unchanged despite Gleevec therapy (Figure 3). The larger,
associated mesenteric density representing a mesenteric
inflammatory mass was also unchanged in appearance. The CT scan was
not helpful in evaluating the response to Gleevec therapy. A PET
scan was done using 20 mCi of 18F-FDG. Whole-body images were
obtained 1 hour after injection. The scan was normal (Figure 3),
and the absence of FDG uptake correlated with the excellent
clinical response and successful therapy for GIST.
A 41-year-old woman presented with intense pain in the left
lower abdominal quadrant. A pelvic ultrasound revealed pelvic
masses that were suspicious for ovarian cancer. The patient had a
total abdominal hysterectomy, bilateral salpingo-oophorectomy, and
partial omentectomy. Pathologic examination of the removed ovarian
masses showed CD117-positive GISTs rather than ovarian cancer.
During laparotomy, large left upper and midabdominal omental masses
were also noted that were unsuspected prior to laparotomy. These
masses were asymptomatic but were unresectable. A PET scan
performed 2 weeks after surgery showed markedly increased uptake in
these masses (Figure 4). Three metastatic liver lesions were also
noted on the PET scan (Figure 4). With proven diagnosis of GISTs,
the patient was started on Gleevec therapy. A PET scan performed 5
weeks after beginning therapy exhibited complete disappearance of
FDG uptake in the abdominal and hepatic lesions (Figure 4),
indicating excellent therapeutic response.
Gastrointestinal stromal tumors are the most common mesenchymal
tumors of the gastrointestinal tract (GIT). About 5000 to 6000 new
cases of GISTs are diagnosed in the United States annually.
These tumors are KIT (CD117)-positive mesenchymal tumors of the
GIT, omentum, and mesentery. KIT (CD117) antigen is the most
important immuno- histochemical feature of a GIST and is very
specific for the diagnosis of a GIST.
KIT is a tyrosine kinase receptor uniformly expressed in GISTs.
Approximately 60% to 70% of GISTs are positive for CD34, 30% to 40%
are positive for smooth muscle actin (SMA), and 5% are positive for
S100 protein. Gastrointestinal stromal tumors can rarely be
positive for desmin. Gastrointestinal stromal tumors are more
common in older individuals (usually >50 years) but can occur in
any age group, and both sexes are affected equally.
Gastrointestinal stromal tumors are most common in the stomach (50%
to 60%), followed by small bowel (20% to 30%), large bowel (10%),
esophagus (<5%), and elsewhere in the abdominal cavity
Tumor behavior varies with the site of origin, tumor size, and
histological appearance. Poor prognostic indicators are advanced
patient age, large tumor size (>5 cm), unresectability, presence
of metastases, tumor necrosis, and high mitotic index.
Tumors of small-bowel origin tend to have more aggressive behavior
and a worse prognosis than tumors originating in other
Mitotically inactive tumors can metastasize, and low mitotic count
does not necessarily rule out malignant behavior.
Therefore, the present trend is to stay away from the term "benign"
for any GIST, with the exception of very small (<1 cm) lesions
found incidentally during abdominal surgery. Any GIST that is
sufficiently large to produce clinical signs and symptoms can
exhibit malignant behavior, including recurrence or metastases,
following the initial treatment.
Tumors found incidentally are usually small with a mean diameter
of 1.5 cm and carry a better prognosis.
Generally, endoluminal tumors produce clinical symptoms earlier
than do extraluminal tumors, increasing the chance of curative
surgery. Generally, <50% of the primary localized GISTs relapse
within the first 5 years of follow-up.
The incidence of metastases at first presentation of a malignant
GIST is approximately 50%.
The liver is the most common site for metastases and recurrence.
Less common locations of metastatic disease include the lungs,
pleura, retroperitoneum, bone, and subcutaneous tissues close to
the laparotomy incision.
Metastases to bone and the lung are uncommon.
Unlike other GIT tumors, lung metastases are uncommon with GISTs.
Metastasis to the thyroid gland has not been reported. One of our
patients had a lesion in the thyroid gland that was found to be an
unrelated primary thyroid cancer.
Typical CT findings are the presence of a large
well-circumscribed tumor arising from the stomach or small bowel
that is usually predominantly extraluminal and has a
heterogeneously enhancing soft-tissue rim surrounding the necrotic
center. Metastases, if present, are usually found in the liver or
peritoneum. Lymph node enlargement is not a common feature of
although it is common for lymphomas of the GIT. The differentiation
from other primary gastrointestinal malignancies can often be made
on CT or histopathologic examination. Lymphomas tend to cause
circumferential mural thickening with homogeneous enhancement
frequently with lymph node enlargement.
Carcinoids are mainly found in the terminal ileum and show
desmoplastic reaction, while carcinomas seem to show local
infiltration and visceral obstruction, especially if large.
However, some tumors may be more difficult to characterize on CT or
histopathologic examination. These include soft-tissue tumors (such
as leiomyosarcoma), intra-abdominal fibromatosis of the bowel wall,
and malignant tumors of nerve sheath and blood vessels.
The evaluation of tumor response to therapy on CT images is
based mainly on the World Health Organization (WHO) guidelines and
the Response Evaluation Criteria in Solid Tumors (RECIST).
In addition to WHO- and RECIST-based lesion size assessments, a
change in HU is another important criterion to evaluate tumor
response to Gleevec. Patients are considered responders if the HU
decreases by >25%. The value of 25% was determined based on
previously published data. A potential problem when assessing HU is
that different contrast agents and varying amounts of contrast may
lead to misinterpretation of HU when comparing CT studies.
Positron emission tomographic scanning with the radiotracer 18F-FDG
can reveal early functional changes in tumor glucose metabolism
that appear to correlate closely with metabolic response to
When compared with CT alone, PET with FDG and PET/CT provided
valuable additional information about the extent and metabolic
activity of the disease process.
The response to drug therapy could be shown as early as 24 hours
after completion of a therapeutic regimen.
Complete surgical excision of the primary tumor is the primary
treatment when complete resection is possible in the absence of
metastatic disease. Because of the high rate of local and distant
recurrence, adjuvant therapy is often indicated. Response to
conventional chemotherapeutic agents and radiation therapy is
disappointing. Early experience with the tyrosine kinase inhibitor,
STI-571 (Gleevec, imatinib mesylate), has been extremely
encouraging. This receptor tyrosine kinase inhibitor inhibits the
activated KIT protein. This agent is now approved for the treatment
of patients with KIT (CD117)-positive unresectable and/or
metastatic malignant GISTs. The effectiveness of such treatment is
clear from published studies; however, randomized controlled trials
have yet to be completed to verify improvement in disease-related
symptoms or increased survival. Clinical trials are now ongoing to
evaluate the benefits of Gleevec on early stages of GISTs following
surgical tumor removal.
The advantage of PET lies in its ability to differentiate active
tumor from a nonviable necrotic tumor mass, malignant from benign
tissue, and recurrent tumor from scar tissue. The use of FDG-PET
may improve our ability to accurately follow response to therapy in
GIST patients treated with surgery, imatinib mesylate, and other
treatment modalities. Though very promising, the number of patients
in our experience and the number of published papers is too small
to definitely assess sensitivity of PET and PET/CT in evaluating
GIST response, as this malignancy is rare. A larger, multicenter
study is required.