A Case Report of an Extraintestinal GIST Presenting as a Giant Abdominopelvic Tumor

CASE REPORT

A 75-year-old female patient came to our hospital with a complaint about abdominal distension and dyspnea. A heterogeneous growth with dimensions of 15 × 15 × 12 cm that completely filled the pelvis and had advanced as far as the abdomen was found by abdominal ultrasound guidance (USG) and computed tomography (CT) (Figure 1). The carbohydrate antigen (CA) tumor markers were above normal, and the carcinoembryonic antigen (CEA) was above midrange (CA 12-5, 52.30 U/mL [normal range, 0–35 U/mL]; CA 15-3, 46.71 U/mL [normal range, 0–25 U/mL]; CA 19-9, 41.61 U/mL [normal range, 0–27 U/mL]; and CEA, 2.19 ng/mL [normal range, 0–4 ng/mL]).

Figure 1.

Abdominopelvic CT with contrast showing the tumor in the largest cross-section.

After completion of routine preoperative examinations, the patient was taken for surgery as an ASA level 3 because of her cardiac and respiratory problems. The exploration conducted with a median laparotomy showed that the 15-cm large growth completely filled the abdominopelvic cavity. The stomach, intestines, liver, spleen, gall bladder and other abdominal organs were of normal appearance. The tumor had a smooth surface with a fragile capsule and was of heterogeneous structure. There were adhesions that could be easily removed by blunt dissection of the omentum, sigmoid colon, uterus, and ovaries. However, the tumor had made a firm invasion into the retroperitoneum. No connection between the intestines and the gynecologic organs was observed. A complete tumor excision was made by dissecting the connections in the pelvic peritoneum. A macroscopic pathologic evaluation of the specimen showed that the lobule was solid, and the cystic areas were heterogeneous in structure and yellow-brown (Figure 2). A microscopic evaluation showed that there were areas of increased chromatin and vesicular nuclei in places and indefinite nucleoli, nuclear pleomorphism, and a large amount (>10 in 50 high-power fields [HPFs]) of mitotic area in others. In some areas there was a narrow cytoplasm, and in others there were atypical epithelioid cells that had a threadlike appearance. (Figure 3). In addition to the atypical pleomorphic and multinuclear cells, regions of necrosis were observed in some areas. Immunohistochemically, both the threadlike and epithelioid areas were c-kit (CD117) and vimentin positive (Figures 4 and 5). Desmin, CD34 and smooth muscle actin (SMA) were found to be negative. The Ki67 proliferative index was approximately 40% (Figure 6). As a result of the macroscopic, microscopic, and histopathologic findings and the immunohistochemical analyses, a diagnosis of high-risk extraintestinal gastrointestinal stromal tumor (GIST) was made. The patient experienced no complications during the postoperative period, and as a result of medical oncologic consultation, adjuvant treatment with imatinib mesylate (Glyvec, Novartis Europharm Ltd., UK) 400 mg/day was started, and the patient was sent home on postoperative day 8.

Figure 2.

Macroscopic view of the resected tumor.

Figure 3.

Epithelioid tumor tissue with nuclear pleomorphism and atypical widespread mitoses (hematoxylin & eosin, ×200).

Figure 4.

CD117 positive immunostaining in tumor cells (CD117: immunoperoxidase, ×200).

Figure 5.

Vimentin-positive immunostaining in tumor cells (vimentin: immunoperoxidase, ×100).

Figure 6.

Ki67 nuclear-positive immunostaining in tumor cells (Ki67: immunoperoxidase, ×100).

DISCUSSION

GISTs appear as CD117/CD34/vimentin-positive tumors in immunohistochemical staining. They occur in the gastrointestinal tract, and because the only CD117/CD34/vimentin-positive cell type is Cajal interstitial cells (ICCs), they are thought to derive from ICCs.^1–3 Because ICCs, which are responsible for peristalsis, are found only in the gastrointestinal system, the specific cells that extraintestinal GISTs derive from should be studied further.^2,4

The GIST has no specific clinical findings and can cause different symptoms according to its localization and tumor size. Because GISTs are resistant to standard chemotherapy and radiotherapy, the most effective current treatment is total excision of the tumor.^2,5 Imatinib mesylate, a tyrosine kinase inhibitor, is recommended in the continuing treatment of GISTs that have not had total excision or in treatment of postoperative recurrences, whereas sunitinib malate is recommended in the treatment of resistant cases.⁵ The tumor size, occurrence of necrosis, excessive mitosis, and high Ki-67 index are poor prognostic factors for GISTs.^2,6 The tumors rarely exceed a diameter of 10 cm. The current study presents a rare 15-cm extraintestinal GIST, localized in the abdominopelvic region. As the diameter of the tumor increases, the growth that occurs in the abdomen can sometimes exert pressure on the nearby organs and can cause symptoms of gastrointestinal obstruction.^2,6 Extraintestinal GISTs occur twice as frequently in female patients as they do in males.⁷ Although the histologic and immunophenotypical characteristics of extraintestinal GISTs do not differ from other GISTs, their degree of malignancy is higher.

Pelvic GISTs can generally be confused with the pelvic metastasis of stomach or colon tumors and ovarian tumors. Radiologic screening methods such as endoscopic examinations, USG, and CT are valuable. In USG and CT imaging, GISTs appear as solid, multilobular growths that are cystic and generally include calcified or necrotic areas.^7,8

Because of their differing behavior, GISTs are not described as benign or malignant, but as low- or high-risk malignancies, according to the diameter and rate of mitosis (NIH 2001).⁹ Those with a diameter smaller than 5 cm with less than 5 mitoses/50 HPFs are classified as low-risk malignancies, and those with greater values are classified as high-risk tumors.⁹ In most cases, the growths have a diameter of less than 10 cm, are round or oval, and are exophytic and soft. High-risk malignancy should be considered in rarely observed calcified or necrotic–ulcerative lesions of larger diameters. The present case was evaluated as falling in the high-risk category, according to the NIH 2001 classification, because of the macroscopic and microscopic characteristics.

A definitive diagnosis of GIST is made by looking at the morphology and the immunohistochemical characteristics, but the tumor can be typed only histopathologically. Three types of GIST have been identified according to cell type: threadlike, epithelioid, and mixed.^2,9 Positive immunohistochemical staining of the tumor is characteristic with CD117, a product of the proto-oncogene c-kit.¹⁰ CD117 is a tyrosine kinase transmembrane receptor found on chromosome 4 (4q11-q12). However, malignant melanoma, liposarcoma, fibrosarcoma, seminoma, hemangiopericytoma, fibrous histiocytoma, Ewing sarcoma, and myofibroblastic tumors can be CD117 positive. On the other hand, some GISTs can be CD117 negative due to the c-kit PDGFRA (platelet-derived growth factor receptor α) mutation.^2,5 In such cases, histopathologic differential diagnosis is carried out with tumor determiners such as desmin and smooth muscle actin (SMA).

The basic method of treatment for GISTs is surgery, and the tumor is totally excised. Standard chemotherapy and radiotherapy are not effective. The protein tyrosine kinase inhibitor imatinib mesylate (Glyvec) is the most important antineoplastic agent used in the current medical treatment of the disease. Daily doses of 400 to 800 mg imatinib mesylate yield successful treatment results and prevent recurrences. In cases that are resistant to imatinib mesylate, the use of sunitinib malate is suggested.^2,11–13