Malignant gastrointestinal stromal tumor presenting with hemoperitoneum in puerperium: report of a case with review of the literature
© Varras et al; licensee BioMed Central Ltd. 2010
Received: 31 March 2010
Accepted: 7 November 2010
Published: 7 November 2010
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that develop in the wall of the gastrointestinal tract and their diagnosis during pregnancy or puerperium is extremely rare.
A 28-year old patient presented with acute abdomen due to hemoperitoneum from a large mass arising of the small intestine with distended vessels on its top and a ruptured superficial vessel bleeding into the peritoneal cavity. The patient was at the tenth postpartum day of her first pregnancy. The preoperative diagnosis was a possible ovarian or uterine mass. After an emergency exploratory laparotomy a segmental bowel resection was performed, removing the tumor with a part of 3-cm of the small intestine. Histology revealed GIST with maximum diameter of 13 cm and mitotic rates more than 5 mitoses per 50 high power fields with some atypical forms, indicating a high risk malignancy. Immunohistochemical staining of the tumor tissue demonstrated strongly positive reactivity to CD 117 (c-kit) and CD34 in almost all the tumor cells. The patient was treated with oral imatinib mesylate (Gleevec) 400 mg daily for one year. Three years after surgery, the patient was alive without evidence of metastases or local recurrence.
Considering that only few patients with gastrointestinal stromal tumors have been reported in the obstetrical and gynecological literature, the awareness of such an entity by the obstetricians-gynecologists is necessary in order to facilitate coordinated approach with the general surgeons and oncologists for the optimal care of the patients.
Gastrointestinal stromal tumors (GISTs) are uncommon tumors that develop in the wall of the gastrointestinal tract and usually present in the fifth to seventh decade of life [1, 2]. They account for approximately 0.1% to 3% of all gastrointestinal neoplasms, with an incidence of 1-20 per million and up to 30% of these are considered malignant [1, 3, 4]. The term gastrointestinal sromal tumor, first used by Mazur and Clark in 1983, encompasses a heterogeneous group of nonepithelial neoplasms composed of spindle or epithelioid cells, which display a range of differentiation . Given the age distribution of occurrence, a diagnosis of gastrointestinal stromal tumor during pregnancy [6–8] or puerperium is very uncommon.
We hereby describe our experience of the case of a GIST discovered during the puerperium, in a 28-year old patient presented with acute abdomen due to spontaneous rupture of a superficial tumor vessel, an extremely rare complication and review the current literature.
The patient's postoperative course was uneventful and she was treated with oral imatinib mesylate (Gleevec) 400 mg daily for one year. Three years after surgery for the primary gastrointestinal stromal tumor, the patient is alive. A recent CT scan of the upper and lower abdomen was negative for local recurrences of the disease or secondary metastases.
GISTs occur anywhere in the intestine, with the most common site being the stomach (50-60%), followed by the small intestine (20-30%), large bowel (10%), the oesophagus (5%), and only 5% elsewhere in the abdominal cavity such as in the mesentery, omentum or retroperitoneum [2, 9].
GISTs may be detected during a gastroscopy as submucosal tumors or occasionally as incidental radiologic findings. The symptomatic GISTs of the esophagus typically present with dysphagia. Gastric and small intestinal GISTs often present with vague symptoms, but sometimes they cause upper gastrointestinal bleeding. Colorectal GISTs may manifest with lower gastrointestinal bleeding, colonic perforation, pain, obstruction or combination [4, 10, 11]. Also, fever or liver metastasis have described as first symptoms . Rarely, they can present with intraperitoneal bleeding secondary to surface tumor ulteration [9, 10]. Our patient presented clinically with pelvic pain and a pelvic mass diagnosed ultasonographically showing adequate fluid in the abdominal and pelvic cavities. The preoperative diagnosis was consistent with acute abdomen from a possible ovarian or uterine tumor. The ultrasonographic findings of GISTs are non-characteristic and therefore a preoperative presumptive diagnosis based on imaging is virtually impossible . In our patient, during the operation, on the top of the mass a ruptured superficial vessel was found to bleed actively into the abdominal cavity and no other bleeding was indentified. It seems that the hemoperitoneum resulting from a solid mass is secondary to passive blood congestion, subsequent rupture of a superficial tumoral vessel and spontaneous internal bleeding . The postpartum hyperfibrinolysis might play a role for the bleeding of the mass. A diagnosis of GIST during pregnancy is very uncommon [6–8]. Those few cases reported were symptomatic and found in the second half of the pregnancy, leading to an emergency cesarean section in one case due to fetal distress during laparotomy [6, 7]. The delay in diagnosis of GISTs during pregnancy is normally due to the clinicians' reluctance to request diagnostic examinations during pregnancy and to the non-specific symptoms of the disease . Our patient had a normal delivery at term at a Private Maternity Hospital of Athens, because no obstruction of labor had occurred obviously. Possibly, the large mass arising from the small intestine and growing exophytically out into the peritoneal cavity was removed outside the pelvis by the pregnant uterus. For the same reason the patient might have tolerated the high pressure during labor and the tumor did not stared bleeding during labor.
Macroscopically, GISTs are usually grey-white in appearance. They arise in the muscularis propria, and can grow either exophytically out into the peritoneum, or endophytically into the lumen of the gut . Microscopically, GISTs are well-circumscribed smooth lobulated, uncapsulated tumours. They are composed of spindle cells or epithelioid cells, or a mixture of both, and may show areas of cystic degeneration, necrosis or focal hemorrhage [Sanjay et al 2004]. The hypothesis that GISTs originate from the primitive stem cell that can differentiate toward the interstitial cells of Cajal, has been advocated. Interstitial cells of Cajal are autonomous nerve-related GI pacemaker cells that regulate intestinal motility and are immunoreactive for a specific immunostain (CD117) of a c-kit proto-oncogene protein (KIT), which encodes for a transmembrane tyrosine-kinase receptor [14–18]. Mutations of c-kit proto-oncogen seem to produce overexpression of the KIT protein, which is responsible for the pathogenesis of GISTs . Also, GISTs are often positive for CD34 and variably positive for smooth muscle actin . Mesenchymal tumors of the uterus and ovaries are thought to rarely express c-kit, but if they do, the staining is usually focal, with fewer than 5% of cells been positive [9, 20, 12]. The final diagnosis of our patient was established based on the intestinal origin of the neoplasm and its histopathologic and immunohistochemical findings. The immunohistochemical analysis showed positive reactivity to the c-kit gene, CD34, a-smooth muscle actin, but no reactivity to S-100 protein.
Management depends on complete surgical resection, incomplete resection being associated with a median survival of less than 20 months. The wide margins of resection are not necessary as there is minimal local invasion and similarly lymphadenectomy is not routinely necessary as local lymph nodes are not usually affected . Various systemic chemotherapeutic regimes, radiation and intraperitoneal chemotherapy has been used with little success . However, Joensuu et al reported the first use of STI-571 (imatinib mesylate, Gleevec) in a case of recurrent metastatic GIST that failed extensive surgical therapy and chemotherapy . The dramatic response in their case was documented both clinically and histologically. They also documented a marked decrease in tumor activity by 18FDG-PET scanning. Shortly after reporting the case, confirmatory data were published [22, 23].
Prognostic factors indicating the possible malignant potential of gastrointestinal tumors are mitotic activity (>5 mitotic figures per 50 × high power field) and tumor size (>5-cm). Tumors that have the c-kit exon 11 mutation are also at greater risk . Tumor rupture before or during surgery has also been linked to poor prognosis [9, 4, 24]. Factors as mucosal invasion and tumor necrosis have found to be related to increased risk of aggressive behavior, but their clinical value remains uncertain . The spread pattern of gastrointestinal tumors with malignant potential shows predilection for liver metastasis and peritoneal dissemination. Therefore, the presence of hepatic or peritoneal lesions on presentation usually represents a sign of poor prognosis [4, 9]. In addition, incomplete surgical resection is associated with a reduced survival . Chemotherapy with imatinib (Gleevec, Novartis, Switzerland) was perfomed in our patient due to the large tumor size (>5-cm), and mitotic activity (>5/50 HPF). Reccurrence or metastasis after complete surgical resection may occur in more than two thirds of all gastrointestinal stromal tumors. Recurrence is usually local or peritoneal and often associated with liver metastases. Most recurrences occur within 2 years of the original tumor, although intervals of up to 10 years have been reported (2). In our case, three years after surgery, the patient was alive and the recent CT scan of the upper and lower abdomen showed no local recurrences of the disease or secondary metastases. Because of limited experience of GISTs diagnosed during pregnancy, no reference is made to the possibility of metastatic disease in the fetus or the developing of GIST in utero.
Since only few patients with gastrointestinal stromal tumors have been reported in the obstetrical and gynecological literature [6, 7, 12, 8, 25–31], the awareness of such an entity by the obstetricians-gynecologists is necessary in order to include this in the differential diagnosis of minor gastrointestinal discomfort during pregnancy and in addition to facilitate coordinated approach with the general surgeons and oncologists for the optimal care of the patients. Complete surgical resection and immediate therapy with imatinib are associated with better survival of patients with such refractory tumors for radiotherapy and conventional chemotherapy. For GISTs diagnosed during pregnancy no reference is made to the possibility of metastatic disease in the fetus or the developing of GIST in utero. For pregnant patients with suspicious tumor findings on ultrasonography, the ultrasound examination should determine the origin of the mass and its location, size and internal structure. For ovarian masses, color Doppler imaging should also be performed. Pelvic MRI with gadolinium injection can be performed after the first trimester to remove any doubt or to provide additional information if the ultrasound examination is not sufficient or as a tool for the assessment of cancer. Pelvic CT scanning is not indicated during pregnancy. Surgery should be immediate considered in cases of acute symptoms or suspicious tumors for malignancy . The best predictor of whether a uterine leiomyoma cause problem during pregnancy is its location. Submucosal leiomyomas interfere with the implantation of the placenta, subserosal feiomyomas present with infarction, while leiomyomas in the cervix or at lower uterine segment may cause obstruction of the labor. Rarely, large submucosal nonpedunculated uterine leiomyoma can interfere with puerpurium by obstructing the passage of lochia and leading to haematometra and uterine atony .
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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