V08_No_2_Final.pdf Case Report 165Urology Journal Vol 8 No 2 Spring 2011 Extragastrointestinal Stromal Tumor of the Urinary Bladder A Case Report Hong-Seok Shin,1 Chang-Ho Cho,2 Yoon-Seup Kum2 Urol J. 2011;8:165-7. www.uj.unrc.ir Keywords: gastrointestinal stromal tumor, urinary bladder, cystoscopy 1Department of Urology, School of Medicine, Catholic University of Daegu, Korea 2Department of Pathology, School of Medicine, Catholic University of Daegu, Korea Corresponding Author: Yoon-Seup Kum, MD Department of Pathology, School of Medicine, Catholic University of Daegu, 3056-6, Daemyung-dong, Nam-gu, Daegu, 705-718, Korea Tel: +82 536 504 159 Fax: +82 536 503 050 E-mail: yskum@cu.ac.kr Received October 2009 Accepted November 2009 INTRODUCTION A gastrointestinal stromal tumor (GIST) is primarily located in the gastrointestinal tract. It is classified as a mesenchymal tumor that shows a CD117 (c-KIT)-positive mesenchymal spindle or epithelioid neoplasm. Tumors outside the gastrointestinal tract that were histologically similar to GISTs and showed immunopositivity for CD117 were classified as extragastrointestinal stromal tumors. Although there were several reports of tumors outside the gastrointestinal tract, only a case of extragastrointestinal stromal tumor in the urinary bladder was reported.(1,2) Herein, we report another case arising in the urinary bladder presenting with submucosal polypoid mass. CASE REPORT A 42-year-old man presented with hematuria since three weeks ago. He had no irritative or obstructive urinary symptoms. Urine analysis was normal and other laboratory studies were within normal limits. Computed tomography scan revealed an intravesical solid polypoid mass measuring 2.6 × 2.4 cm and multiple small calcified spots in the bladder base (Figure 1). No no evidence of an intra or extraluminal mass was observed in the gastrointestinal tract. The patient was taken to the operating room for a cystoscopic examination. A thumb tip-adult size polypoid submucosal mass with a smooth surface mucosa and a broad base was detected in the bladder dome. Thereafter, the mass was cystoscopically removed. The cystoscopically resected specimen consisted of multiple chips of yellow, pink, and gray, soft rubbery tissue, measuring 3.0 × 2.0 × 2.0 cm in aggregate. Tumor cells were found to be scattered in Figure 1. Computed tomography scan revealed an intravesical polypoid mass with small multiple calcified spots within the contrast-filled urinary bladder lumen. Extragastrointestinal Stromal Tumor—Shin et al 166 Urology Journal Vol 8 No 2 Spring 2011 the submucosa, and the overlying transitional epithelium was intact without ulceration. It was composed of sheets or nests of eosinophilic cells without any organoid features and loose edematous well-vascularized stroma, and with varied cellularity (Figure 2). In some areas, the tumor cells proliferated along the abundant vascular structures, and were arranged in a perithelial pattern. Occasionally, individually- scattered tumor cells were noted in the edematous stroma. The tumor cells were chiefly composed of polygonal epithelioid cells and were rarely composed of little spindle cells. The nuclei were ovoid or round and often centrally located. Some had bland or hyperchromatic nuclei. Occasionally, intranuclear inclusion bodies were noted. The cytoplasms were bright plump eosinophilic with relatively distinct cytoplasmic margins; occasionally, irregular margins were observed. Furthermore, eosinophilic cytoplasms were not stained by periodic acid-Schiff staining. Neither mitosis nor necrosis was observed. The stroma had a loose edematous myxoid or a focally liquefied appearance with high vascularity. Immunohistochemically, the tumor cells strongly expressed CD117 (Figure 3) and weakly expressed CD34, but they were negative for smooth muscle actin, pan-cytokeratin, and S-100 protein. During 20-month follow-up, using transabdominal ultrasonography and cystoscopic examination, no recurrence of tumor growth was noted. DISCUSSION Most of the GISTs were previously classified as leiomyoma or neurogenic tumors because of similar histologic and immunophenotypic features of smooth muscle or neurogenic differentiation.(3) Recently, however, they expressed a growth factor receptor with tyrosine kinase activity, known as KIT, which appeared to play a key role in committing primitive mesenchymal cells towards interstitial cells of Cajal differentiation.(3,4) True neural and smooth muscle neoplasms of the gastrointestinal tract entirely lack KIT mutations. Some GISTs contain activating mutations in the KIT proto-oncogene, which appears to be a strong candidate for the molecular pathogenesis of GISTs.(5) Therefore, KIT expression was proposed to be both the most sensitive and specific phenotypic marker of GISTs showing differentiation towards the interstitial cell of Cajal.(4) Extragastrointestinal stromal tumors are relatively rare compared with their gastrointestinal counterpart. Approximately, 7% of the tumors occurred in the soft tissues of the peritoneum, omentum, and mesentery.(6) Extragastrointestinal stromal tumors usually present during adult life in the form of enlarging masses with variable duration. Unlike their gastrointestinal counterparts, these lesions tend to be large when are first detected. Most of them are firm, fleshy, grey, and red masses with occasionally cystic change. Figure 2. The tumor shows sheet or nests of polygonal epithelioid cells having bland or hyperchromatic nuclei and bright eosinophilic cytoplasms with relatively distinct cytoplasmic margins (hematoxylin and eosin stain ×100). Figure 3. The stain-positive tumor cells for CD117 (Immunohistochemical stain, × 200). Extragastrointestinal Stromal Tumor—Shin et al 167Urology Journal Vol 8 No 2 Spring 2011 Histologically, there are two types; epithelioid and spindle cells. The former is noted where the tumor is composed of round cells with varying pleomorphic cell size and an eosinophilic or clear cytoplasm. The nuclei are uniform and round to ovoid, and have a vesicular chromatin. Occasionally, hyperchromatism, multinucleation, a prominent cytoplasmic vacuole, and a peripherally located nucleus are also seen. The epithelioid type was previously classified as leiomyoblastoma. The spindle pattern more closely resembles the conventional smooth muscle tumors, which are short and fusiform in contrast to the smooth muscle cells that show short fascicles and whorls, and their nuclei tend to be uniform and round.(3) In addition to the fact that the cells were consistent positive for KIT (CD117), some GISTs showed immunopositivity for CD34 and S-100 protein and were rarely positive for smooth muscle actin and desmin. The clinical behavior of an extragastrointestinal stromal tumor is difficult to predict. However, it is well-accepted that the malignant behavior of GISTs is strongly correlated with tumor size (> 5 cm in greatest diameter) and mitotic count on this rule, our case is benign. However, it should be noted that the lesions that are very small (even < 2 cm) and have low mitotic rates (even < 5 per 50 high-power field) occasionally metastasize.(3) Therefore, a prolonged follow-up period is necessary for almost any GIST that exhibits the potential to behave in a malignant fashion. It was known that there was no effective therapy except complete surgical resection until the recent development of the KIT inhibitor imatinib mesylate. This inhibitor attacks a specific molecular target in GISTs, by employing tyrosine kinase of KIT inhibition as well as disrupting signal transduction at mitosis. It induces growth arrest and apoptosis of tumor cells.(7) CONFLICT OF INTEREST None declared. REFERENCES 1. Kobayashi T, Teruya M, Shimizu S, et al. Giant extragastrointestinal stromal tumor. Am J Surg. 2004;188:191-2. 2. Mekni A, Chelly I, Azzouz H, et al. Extragastrointestinal stromal tumor of the urinary wall bladder: case report and review of the literature. Pathologica. 2008;100:173-5. 3. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol. 2002;33:459-65. 4. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577-80. 5. Nasu K, Ueda T, Kai S, et al. Gastrointestinal stromal tumor arising in the rectovaginal septum. Int J Gynecol Cancer. 2004;14:373-7. 6. Emory TS, Sobin LH, Lukes L, Lee DH, O’Leary TJ. Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. Am J Surg Pathol. 1999;23:82-7. 7. Dematteo RP, Heinrich MC, El-Rifai WM, Demetri G. Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol. 2002;33:466-77.