Arch Gynecol Obstet (2008) 278:89–92 DOI 10.1007/s00404-007-0528-9
C A S E RE P O RT
Unusually large extraintestinal GIST presenting as an abdomino-pelvic tumor Diana Matteo · Vani Dandolu · Larissa Lembert · Rebecca M. Thomas · Ashwin J. Chatwani
Received: 25 September 2007 / Accepted: 20 November 2007 / Published online: 8 December 2007 © Springer-Verlag 2007
Abstract Background Gastrointestinal stromal tumor (GIST) is a rare visceral tumor that may mimic ovarian tumor. Case A 56-year-old woman presented with a large abdomino-pelvic mass and moderately elevated CA-125. A large tumor occupying the whole abdominal cavity and pelvis was noted on laparotomy. In addition, multiple tumor nodules were seen from the ligament of Treitz to the terminal ileum involving only the surface intestine. The ovaries appeared normal. The tumor demonstrated spindle and epithelioid components and was found to be morphologically and immunohistochemically consistent with GIST. Conclusion Gynecologists need to be cognizant of extraovarian pathology in the atypical presentation of a pelvic mass. Correct diagnosis is essential for proper management since GISTs speciWcally respond to the c-kit selective tyrosine kinase inhibitor, Imatinib mesylate. Keywords GIST · Gastrointestinal stromal tumor · Extraintestinal GIST
Background Gastrointestinal stromal tumors (GISTs) are rare visceral neoplasms that arise from the gastrointestinal (GI) tract and most often express immunoreactivity for CD117, a c-kit proto-oncogene protein [1]. Although rare, they are the most common mesenchymal neoplasms of the GI tract [2].
D. Matteo · V. Dandolu (&) · L. Lembert · R. M. Thomas · A. J. Chatwani Temple University School of Medicine, Philadelphia, PA 19140, USA e-mail:
[email protected]
The primary site is usually the stomach or small intestine, with a smaller percentage of tumors originating in the colon, rectum, appendix, esophagus, and other locations [3]. Many of these tumors are found in patients in their Wfth or sixth decade of life [4]. The cell of origin of GIST is thought to be the interstitial cell of Cajal (ICC), the pacemaker cell that controls GI peristalsis. ICC is the only known CD117/CD34/vimentin-positive cell in the GI tract; since GISTs are almost always CD117/CD34/vimentinpositive, it has been proposed that GISTs originate from the ICC [5]. Extraintestinal GISTs have been reported rarely [7], and the cell of origin in these locations is uncertain. Surgical resection is the treatment of choice for tumors that can be completely resected because GISTs are typically resistant to standard chemotherapy and radiation treatment [6]. Imatinib mesylate, a drug which was approved for use in 2001, is a tyrosine kinase inhibitor that has been shown to shrink tumor size and is used in cases where surgery is not a feasible option or following surgery in patients with high-risk GIST [6]. Another breakthrough in GIST therapy is sunitinib malate, which was approved by the U.S. Food and Drug Administration in 2006 for the treatment of GIST in those patients resistant to imatinib mesylate [6]. Large tumor size, increased mitotic rate, tumor necrosis, and a high Ki-67 index have been associated with malignancy and are accepted as the main prognostic features to predict the risk of metastasis and mortality [1]. The majority of GISTs are less than 10 cm in size. We report the case of an unusually large tumor with characteristics of GIST presenting as a pelvic tumor.
Case A 56 years old, African American woman, gravida 7 para 5, presented with shortness of breath and abdominal distension.
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Fig. 3 Epithelioid tumor cells with mitotic Wgures (hematoxylin and eosin stain; magniWcation £200) Fig. 1 Spindled tumor cells in fascicles (hematoxylin and eosin stain; magniWcation £100)
Fig. 2 Spindled tumor cells with atypical, pleomorphic nuclei (hematoxylin and eosin stain; magniWcation £400)
Fig. 4 c-kit positive immunostaining in the spindled areas (magniWcation £200)
A CAT scan done a month prior demonstrated a large, heterogeneously enhancing mass measuring 31 £ 24 £ 21 cm, with both cystic and solid components, arising from the pelvis. The patient had had an abdominal hysterectomy in the past. A transvaginal ultrasound conWrmed the lower end of the very large abdominal pelvic mass, but the ovaries could not be visualized. CA 125 was moderately elevated at 55 units/ml. The patient underwent an exploratory laparotomy for a presumed ovarian tumor. There was a large mass 30 £ 30 cm, occupying the whole of the abdominal cavity. There was another large mass of approximately 15 cm in the right upper quadrant, just posterior to the hepatic Xexure, abutting the distal stomach, Wrmly attached to the superior portion of the hepatic Xexure and extending from the
pelvis to the undersurface of the liver; this did not appear to arise from the liver, gallbladder, or biliary structures. The mass was resected by dissecting in a circumferential fashion around the tumor. Normal ovaries were noted bilaterally after the removal of the mass; however, a left oophorectomy was performed because of initial suspicion of a primary ovarian carcinoma. The right ovary was noted to be atrophic and was not removed. An appendectomy was performed to rule out appendiceal primary. Total infracolic omentectomy was also performed. There was another 6–7 cm mass beneath the right lobe of the liver in the lesser sac. The lesser sac was opened and the tumor was sharply and bluntly dissected oV from the surrounding tissue. The tumor was adherent to the stomach, but did not seem to arise from the stomach or colon. The liver, spleen, kidneys, and bladder appeared normal. In addition, multiple tumor
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Microscopically, the tumor was composed of fascicles with spindled and epithelioid morphology. The spindled areas ranged in cellularity from moderate to extremely cellular with scattered areas of necrosis; the atypia ranged from mild to severe with some bizarre, large pleomorphic cells. The mitotic activity was most in the epithelioid areas, with mitotic counts of up to 18 per high power Weld (HPF). Immunohistochemical studies were performed; vimentin, CD34 and c-kit (CD117) were positive on both the spindled and epithelioid areas; AE1/3, desmin, myoglobin and smooth muscle actin (SMA) were negative. The morphology and immunohistochemical proWle of this tumor was therefore diagnostic of a malignant GIST (Figs. 1, 2, 3)
Comment Fig. 5 c-kit postitive immunostaining in the epithelioid areas (magniWcation £200)
nodules were seen throughout the peritoneal cavity including the surface of the small and large intestine, stomach and mesentery. The nodules were 1–2 cm in size and were observed from the ligament of Treitz to the terminal ileum. The pancreatic head was normal, and there was no tumor seen in the proximal stomach or in the left upper quadrant. There was no bowel obstruction. Because there were extensive metastatic deposits throughout the abdominal cavity, radical debulking was avoided. The patient’s abdomen and pelvis were irrigated and closed and the patient was transferred to the surgical intensive care unit where she was closely monitored. Her recovery was uneventful and she was discharged home on the ninth postoperative day. Prior to discharge, patient was seen by a medical oncologist and started on Imatinib mesylate (Gleevec® or STI571 from Novartis). Now, she is 6-month post-surgery and symptom free on 400 mg once daily dose of Gleevec®. CT scan 4-month post-surgery did not show residual tumor and again ovaries were not visualized. Plan is to continue Gleevec® indeWnitely. The tumor was submitted to Pathology as multiple specimens. The Wrst specimen measured 15 £ 14 cm and weighed 903 g, and the second measured 30 £ 30 cm and weighed 5,700 g; intraoperative consultations were performed in the Pathology Laboratory on both. These specimens were yellow-tan, Wrm and lobulated with cystic and hemorrhagic areas; the omentum had multiple yellow-tan nodules, measuring up to 6 cm in greatest dimension; the mesenteric mass was 9.5 cm in greatest dimension; the remainder of specimens (ovaries, appendix, abdominal wall and peritoneal implants, and mesenteric nodule) showed tumor of similar gross appearance, ranging from 0.5 to 5 cm.
The current case illustrates one of the largest reported extraintestinal GIST mimicking an ovarian tumor. GIST rarely presents as a pelvic mass and may be mistakenly diagnosed as an ovarian tumor [7]. The diagnosis of GIST was established based on morphology and immunophenotype. Histologically, there are three types of GISTs: spindle celled (70%), epithelioid (20%), and mixed [8]. The tumor in this case was mixed, exhibiting both spindle and epithelioid components and was immunopositive for c-kit. Approximately 95% of GISTs carry an activating somatic mutation of CD117 (c-kit) [5]. CD117 is the product of proto-oncogene c-kit, a tyrosine kinase transmembrane receptor located on chromosome 4 (4q11-q12) [9]. Positive immunohistochemical staining for CD117 is a deWning feature of GISTs [9]; however, there are GIST tumors that have a mutation of PDGFRA instead of c-kit and therefore do not show the characteristic CD117 positive immunostaining. c-kit positive tumors are most responsive to the treatment with the c-kit selective tyrosine kinase inhibitor, Gleevec or Imatinib mesylate; some reports support a therapeutic trial of Gleevec for all GIST patients regardless of CD117 expression [10] (Figs. 4, 5). There are other neoplasms in which CD117 expression is detected. These include melanoma, dermatoWbrosarcoma, protuberans, seminoma, liposarcoma, malignant Wbrous histiocytoma, myoWbrosarcoma, hemangiopericytoma, Wbrosarcoma, Wbromatoses, inXammatory myoWbroblastic tumors, Ewing’s sarcoma, synovial sarcoma, and others [6]. The characteristic morphology with the panel of immunohistochemical markers helps to rule out these diagnoses. Tumors with smooth muscle or neurogenic origin have a similar morphology but do not express CD117; they do express desmin and/or SMA; since this tumor was negative for desmin and SMA, the diagnosis of leiomyosarcoma was ruled out in this case.
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No characteristic biochemical markers nor typical imaging features have been described. On ultrasound, GISTs appear as well deWned or polylobulated solid tumors with occasional cystic changes, necrosis, or calciWcations. On CT studies, they are described as soft tissue masses, that are well-deWned, round or oval, exophytic, and smaller than 5 cm. Larger size, calciWcation, necrosis, and ulceration were seen in intermediate and high risk tumors. Because the terms benign and malignant do not fully describe the behavior of GIST, the National Institutes of Health (NIH) developed a new classiWcation system for risk of malignant behavior in 2001. The scale ranges from very low risk to high risk and is based on tumor size and mitotic count [6]. In general, tumors larger than 5 cm, with more than 5 mitoses/50 HPFs are considered to be high risk. This case is unique because of the extremely large tumor size which was 31 £ 24 £ 21 cm; in other studies mean tumor size has been reported to range from 6 to 10.6 cm [5, 11]; there was also a very high mitotic rate of up to 18/HPF. The presence of coagulative necrosis such as seen in this case has been found to be strongly associated with malignant behavior by many researchers [4]. GISTs are tumors with remarkable variability in diVerentiation pathways. They can diVerentiate into smooth muscle, neural elements, both (dual diVerentiation) or none (GIST per se). Although primary peritoneal tumors occur, these are more common in the setting of Type 1 neuroWbromatosis (von Recklinghausen syndrome) [12]. Additional risk factors may include familial urticaria pigmentosa and a rare instance of a familial GIST [13]. Peritoneal involvement by GIST is most often due to metastatic spread from a primary GI site, even if that primary has not been found at the time of presentation of the peritoneal tumor [14]. One study found that 69% of GISTs to be symptomatic. Smaller tumors are less likely to produce symptoms [6]. Common symptoms of GIST include pain, palpable mass, GI bleeding, and signs of bowel obstruction [1]. When present as pelvic tumors, they are often thought to be ovarian in origin, metastatic to the GI tract. When confronted with an atypical pelvic mass, the possibility of diseases other than primary ovarian tumors needs to be entertained. Metastatic tumors account for approximately 17% of ovarian malignant tumors and are of GI origin in 24–42% of cases [3]. Metastatic tumors may mimic primary ovarian neoplasms and are often unrecognized preoperatively. A diagnosis of GIST should be considered when a spindled or epithelioid morphology is encountered, particularly when there is involvement of the GI tract [7]. Appropriate
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immunohistochemical tests will help to conWrm the diagnosis and ensure proper treatment. Due to the recent advances in the treatment of GIST, making the correct diagnosis is crucial, to ensure the best prognosis.
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