The Turkish Journal of Gastroenterology
Turk J Gastroenterol 2011; 22 (6): 617-620
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|Extra-gastrointestinal stromal tumor presenting
as a surgical emergency
|Yasser Maher AL-JEHANI, Hanan Ibrahim BOUSBAIT, Bina Ravi KANT
|Department of General Surgery, King Fahd Hospital of the University, of Al-Khobar/Eastern Province, Saudi Arabia
|Keywords: Acute abdomen, gastrointestinal stromal tumor, extra-(E)GIST, KIT mutation.
Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. These tumors are present
in almost all cases of KIT-CD117 mutations. When located outside the gastrointestinal tract, they are referred to as extra-gastrointestinal
stromal tumors. We present a case of a 72-year-old female with acute abdomen. Computed tomography detected intestinal
obstruction and failed to determine the causative pathology. The patient underwent urgent exploratory laparotomy, which revealed
pelvic extra-gastrointestinal tumor originating from the broad ligament of the uterus. This case is unique with regard to symptoms
and the unusual anatomic location of the mass. Surgeons should be aware of the extra-gastrointestinal stromal tumor entity and
its manifestations and management.
Gastrointestinal stromal tumors (GISTs) are infrequent
mesenchymal malignancies arising from the
gastrointestinal tract (GIT), accounting for only
0.2% of all GI malignant neoplasms (1). Approximately
60% of GISTs arise in the stomach, 30% in
the jejunum and ileum, 4-5% in the duodenum, 4%
in the rectum, 1-2% in the colon and appendix, and
<1% in the esophagus. Their estimated incidence,
including incidental neoplasm, is 10-20 per million
(2). The majority are characterized by the oncogenic
mutation in either of the two related receptor
tyrosine kinases: KIT-CD117 (75-80%) or PDGFRA
(platelet-derived growth factor) (5-10%) (3). Recently,
extra-gastrointestinal stromal tumors
(EGISTs) showing features of GIST have been described
at extra-gastrointestinal sites including the
omentum, mesentery and retroperitoneal space
(4,5). The clinical features and treatment of
EGISTs are not well known since there have been
only a few cases. To the best of our knowledge, there
has been no report of a primary EGIST originating
from the broad ligament of the uterus.
A 72-year-old female presented to the Emergency
Room in 2008 with a three-day history of vomiting,
diffuse abdominal pain and distention, and diarrhea
and fever for one day, prior to her presentation.
She was a known case of hypertension, diabetes
mellitus, dyslipidemia, chronic obstructive pulmonary
disease (COPD), cardiomyopathy, and
chronic antral gastritis. Her vital signs included:
temperature 39.8°C, pulse rate 110 bpm and blood
pressure 176/83 mmHg. On physical examination,
there were basal crepitations over both lung bases.
The abdomen was distended with generalized tenderness.
There was no guarding or rigidity and the
bowel sounds were absent. Rectal examination revealed
empty rectum and no masses or blood in the
stool. Laboratory findings showed normal complete
blood count (CBC), renal function tests (RFT),
random blood glucose level of 170 mg/dl, erythrocyte
sedimentation rate (ESR) of 62 mm/h, metabolic
alkalosis, O2 saturation: 90.9%, and slight elevation
of total bilirubin (1.4 mg/dl) and lactate dehydrogenase
(LDH: 215 IU/L). The tumor markers
carcinoembryonic antigen (CEA) and alpha fetoprotein
(AFP) were within the normal range. Chest
X-ray showed no lesion. Abdominal X-ray (erect)
showed a picture of subacute intestinal obstruction.
Computed tomography (CT) (abdomen and pelvis)
with intravenous (IV) and oral contrast (Figure
1) was done and showed hypodense liver lesion
in the left lobe with a few hypodense mesenteric
lymph nodal enlargements. Small bowel loops were
dilated, fluid-filled and matted in the pelvic region
with no passage of oral contrast seen beyond
the proximal duodenum. There was difficulty in
outlining the posterior margin of the urinary bladder.
Mesenteric fat stranding was seen along with
multiple peritoneal nodules. She underwent exploratory
laparotomy. The proximal part of the small
bowel was distended with a collapsed distal part.
There was a huge pelvi-abdominal mass (15x12x7
cm) originating from the broad ligament of the uterus,
which was encapsulated, fragile, vascular, adherent
to different areas of the small intestine, vesicoureteric
pouch, uterus, and right adnexa, and
extended to the left adnexa (Figure 2). There were
two obstructive adhesive bands that were released.
Debulking of the mass was performed along with
partial hysterectomy and bilateral salpingo-oophorectomy.
The pouch of Douglas was free. There were multiple areas of metastasis including multiple
small nodules on the anti-mesenteric side of the
ileum, mesentery, dome of the bladder, right lateral
pelvic wall, and omentum. The left lobe of the
liver was palpated as having a parenchymal nodule
of 2 x 3 cm, and a biopsy was taken. The histopathological
diagnosis (Figure 3) of the mass,
omentum and mesenteric implant was mesenchymal
tumor consisted of spindle cells arranged in
interlacing fascicles with foci of necrosis. Most of
the mitotic figures were more than 5 per 50 highpower
field (HPF). The neoplastic cells showed
strong positive immunoreactivity for CD117 (c-kit)
and vimentin and mild positive reactivity for CD34
and were negative for S100 and smooth muscle
markers. Both tubes, ovaries and uterus were unremarkable.
Liver biopsy was negative for malignancy.
Molecular genetic analysis for KIT protein
mutation was not performed due to its unavailability
in our hospital. The diagnosis of EGIST was
made and the patient was started on Glivec (Imatinib)
400 mg PO OD. Two weeks post-operatively,
the patient developed wound dehiscence for which
revision and vacuum- assisted closure (VAC) device
were used. Forty-five days’ postoperatively, the
patient developed respiratory distress. Chest X-ray
was performed and confirmed the presence of bilateral
pleural effusion with partial lung collapse.
The patient died shortly thereafter because of refractory
pulmonary edema in addition to her poor
Extra-gastrointestinal tumor (EGIST) is a rare
stromal tumor that occurs outside the GIT and
comprises about 5-7% of all GISTs (6). The clinical,
pathological and prognostic features of GISTs
are widely known, while data about EGISTs are
few. Most of the EGIST cases are located in the
mesentery, omentum and retroperitoneum (4,5).
There are rare cases of EGIST localization in the
posterior mediastinum, liver, gallbladder, pancreas,
urinary bladder, inguinal hernia sac, scrotum,
uterus, fallopian tube, and rectovaginal septum,
and another report of recurrent vaginal EGIST (7-
17). These tumors could represent apparent
GISTs that have arisen from the outermost muscle
coat of the bowel, but have lost their contact to
the point of origin due to an extensive extramural
growth pattern (18).
Histologically, EGIST can be of spindle cell, epithelioid
or mixed type. The spindle cell type, as present
in our case, is the most common (6). In a large
study, Reith et al. (5) noted that these EGIST expressed
CD117 (100%), CD34 (50%), neuron-specific
enolase (44%), smooth muscle actin (26%), desmin
(4%), and S-100 protein (4%). Due to the rarity
of the EGIST in the pelvic cavity, particularly adjacent
to the female genital tract, and because the
entity of EGIST has only recently appeared,
EGIST might be excluded from the differential diagnosis
of spindle-cell neoplasms and could be confused
with the more common leiomyoma or leiomyosarcoma.
Ortiz-Rey et al. (19) reported that when
detected early, many cases of EGISTs can be accessible
by a fine needle aspiration biopsy (FNAB).
The behavior of stromal tumors differs according to
location, with a trend toward increasingly aggressive
behavior as they proceed distally along the
GIT (5). In this regard, EGISTs are similar to stromal
tumors arising in the distal GIT. Reith et al.
(5) reported that frequent mitotic activity (>2/50
HPF), high cellularity and the presence of necrosis
were factors indicative of a potentially aggressive
clinical course for EGIST. Only 5% of patients with
less than two of the above three histologic features
experienced adverse outcome (death or tumor metastasis),
while 92% of patients having two or more
of the features had an adverse outcome (5). Our
patient displayed high-risk features (mitotic activity
>5/50 HPF, presence of necrosis, moderate cellularity).
In Yamamoto et al.’s (6) study, a high mitotic
rate (>5/50 HPF) and a high Ki-67 labeling index
(>10%) were each significantly associated with
an adverse outcome. EGISTs appear to have enough
space to grow. Therefore, tumor size, which is
commonly used in GISTs as a prognostic factor,
may not be applicable to EGISTs.
The current definitive treatment for GIST, including
EGIST, is surgical resection, with postoperative
recurrence seen in 50% of cases of GIST treated
with surgery alone (20). Lymphadenectomy is
not required, because lymph-node metastasis of
GIST is rare (21). Conventional chemotherapy and
radiotherapy have been reported to be ineffective
in the treatment of GIST. Imatinib, a tyrosine kinase
inhibitor, has been confirmed to be an effective
treatment against metastatic and unresectable
GIST (22). The development of imatinib resistance
is a common occurrence in the clinical management
of GISTs, in which case, novel tyrosine kinase
inhibitor SU11248 (Sutent™) has been proven
to be effective (15).
In conclusion, surgeons as well as diagnostic pathologists
should be aware of the possibility that
this rare tumor can manifest as a pelvic mass with
acute abdomen. Recognition of microscopic patterns
and the characteristic immunohistochemical
phenotype is mandatory for establishing the correct
diagnosis. An aggressive surgical approach is
the most effective treatment. Further studies will
be necessary to clarify the management and biological
behavior of these rare tumors.
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