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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.
Summary
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.
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  • Summary
  • Introduction
  • Case Presentation
  • Discussion
  • References
  • Introduction
    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.
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  • Summary
  • Introduction
  • Case Presentation
  • Discussion
  • References
  • Case Presentation
    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 general condition.
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  • Case Presentation
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  • Discussion
    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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  • Summary
  • Introduction
  • Case Presentation
  • Discussion
  • References
  • References
    1. Loong HH. Gastro-intestinal stromal tumours: a review of current management options. Hong Kong Med J 2007; 13: 61-5.

    2. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagno Pathol 2006; 23: 70-83.

    3. Rubin BP, Heinrich MC, Corless CL. Gastrointestinal stromal tumour. Lancet 2007; 369: 1731-41.

    4. 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: 1109-18.

    5. Reith JD, Goldblum JR, Lyles RH, Weiss SW. Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol 2000; 13: 577-85.

    6. Yamamoto H, Oda Y, Kawaguchi K, et al. c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue). Am J Surg Pathol 2004; 28: 479-88.

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    10. Yamaura K, Kato K, Miyazawa M, et al. Stromal tumor of the pancreas with expression of c-kit protein: report of a case. J Gastroenterol Hepatol 2004; 19: 467-70.

    11. Krokowski M, Jocham D, Choi H, et al. Malignant extragastrointestinal stromal tumor of bladder. J Urol 2003; 169: 1790- 1.

    12. Goyal A, Mansel RE, Goyal S. Gastrointestinal stromal tumour in an inguinal hernia sac: an unusual presentation. Postgrad Med J 2003; 79: 707-8.

    13. Kang SH, Kim MJ, Park MG, et al. Extragastrointestinal stromal tumor presenting as a scrotal mass: an unusual case. Asian J Androl 2007; 9(2): 275-9.

    14. Wingen CBM, Pauwels PAA, Debiec-Rychter M, et al. Uterine gastrointestinal stromal tumour (GIST). Gynaecol Oncol 2005; 97: 970-2.

    15. Foster R, Solano S, Mahoney J, et al. Reclassification of a tubal leiomyosarcoma as an eGIST by molecular evaluation of c-KIT. Gynaecol Oncol 2006; 101: 363-6.

    16. Nasu K, Ueda T, Kai S, et al. Gastrointestinal stromal tumor arising in the rectovaginal septum. Int J Gynecol Cancer 2004; 14: 373-7.

    17. Ceballos KM, Francis JA, Mazurka JL. Gastrointestinal stromal tumor presenting as a recurrent vaginal mass. Arch Pathol Lab Med 2004; 128: 1442-4.

    18. Agaimy A, Wunsch PH. Gastrointestinal stromal tumors: a regular origin in the muscularis propria, but an extremely diverse gross presentation: a review of 200 cases to critically re-evaluate the concept of so-called extra-gastrointestinal stromal tumors. Langenbecks Arch Surg 2006; 319(4): 322-9.

    19. Ortiz-Rey JA, Fernandez GC, Magdalena CJ, et al. Fine needle aspiration appearance of extragastrointestinal stromal tumor. A case report. Acta Cytol 2003; 47: 490-4.

    20. De Matteo RP, Lewis JJ, Leung D, et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 2000; 231: 51-8.

    21. Bray JY, Bonvalot S, Casali P, et al. Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST consensus conference of 20-21 March 2004, under the auspices of ESMO. Ann Oncol 2005; 16: 566-78.

    22. Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 2001; 344: 1052-6.
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  • Summary
  • Introduction
  • Case Presentation
  • Discussion
  • References
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