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Synchronous Large Gastrointestinal Stromal Tumor and Adenocarcinoma in the Stomach Treated with Imatinib Mesylate Followed by Total Gastrectomy

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Synchronous Large Gastrointestinal Stromal Tumor and Adenocarcinoma in the Stomach Treated with Imatinib Mesylate Followed by Total Gastrectomy ANTICANCER RESEARCH 36: 1855-1860 (2016) Synchronous Large Gastrointestinal Stromal Tumor and Adenocarcinoma in the Stomach Treated with Imatinib Mesylate Followed by Total Gastrectomy TSUTOMU NAMIKAWA1, ERI MUNEKAGE1, MASAYA MUNEKAGE1, MICHIHIRO MAEDA2, TOMOAKI YATABE3, HIROYUKI KITAGAWA1, KOUICHI SAKAMOTO1, MASAYUKI OBATAKE1, MICHIYA KOBAYASHI2,4 and KAZUHIRO HANAZAKI1 Departments of 1Surgery, 3Anesthesiology, and 4Human Health and Medical Sciences, Kochi Medical School, Kochi, Japan; 2Cancer Treatment Center, Kochi Medical School Hospital, Kochi, Japan Abstract. Herein we report on a case of synchronous large Gastrointestinal stromal tumors (GISTs) are the most common gastrointestinal stromal tumor (GIST) and adenocarcinoma of mesenchymal tumor of the gastrointestinal (GI) tract and are the stomach treated with radical surgery following believed to arise from precursor interstitial cells of Cajal. neoadjuvant therapy with imatinib mesylate. A 58-year-old GISTs are most commonly found in the stomach, accounting man was referred to our hospital with a large mass in the for 0.1-3% of all GI malignancies, and can be characterized at peritoneal cavity. Abdominal computed tomography showed a the molecular level by activating mutations in the receptor large mass measuring 21×20×14 cm in the left upper tyrosine kinases KIT proto-oncogene receptor tyrosine kinase peritoneal cavity. Esophagogastroduodenoscopy revealed a (KIT) and platelet-derived growth factor receptor-α (PDGFRA) large elevated lesion in the upper body and a depressed lesion (1). Adenocarcinoma is the most common histological type of in the lower gastric body near the lesser curvature. Biopsy malignancy in the stomach. Adenocarcinoma can coexist with specimens revealed GIST in the large elevated lesion and another synchronous tumor of a different histological type in a signet-ring cell carcinoma in the depressed lesion. Because of different part of the stomach. The synchronous occurrence of the large size of the GIST, the patient was treated with tumors of different histological types in the stomach has neoadjuvant therapy with imatinib mesylate (400 mg/day) for recently become the subject of increasing interest. Synchronous 5 months. After confirmation of a marked decrease in tumor occurrence of GIST and adenocarcinoma in the stomach is size following imatinib mesylate therapy, the patient uncommon, with only a few patients with GIST and underwent total gastrectomy and regional lymph-node synchronous gastric cancer described in the literature. dissection with distal pancreatectomy and splenectomy. A novel treatment strategy for locally advanced or metastatic Pathological examination confirmed the diagnosis of high-risk GIST is the use of different tyrosine kinase inhibitors (e.g. GIST and signet-ring cell carcinoma invading the muscularis imatinib) to inhibit growth factor receptor c-KIT tyrosine propria with one lymph-node metastasis. At the time of kinase. Neoadjuvant treatment in patients who present with writing, the patient was receiving postoperative chemotherapy inoperable GISTs may enable successful and less radical using oral fluoropyrimidine (S-1) without evidence of disease surgery after cytoreduction. Herein we report a case of a patient recurrence for 4 months after surgery. In addition to the with synchronous large GIST and adenocarcinoma of the present case, we provide a retrospective review of another 15 stomach treated by surgery after 5 months of neoadjuvant patients who were diagnosed with synchronous GIST in the therapy with imatinib mesylate, a tyrosine kinase inhibitor. In stomach and primary gastric adenocarcinoma. addition, we review previously published case reports of synchronous large GIST and adenocarcinoma of the stomach. Case Report Correspondence to: Tsutomu Namikawa, Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783- A 58-year-old Japanese man visited his local doctor 8505, Japan. Tel: +81 888802370, Fax: +81 888802371, e-mail: [email protected] complaining of abdominal discomfort. Abdominal ultrasono- graphy revealed a large mass in the peritoneal cavity and the Key Words: Gastrointestinal stromal tumor, adenocarcinoma, signet patient was referred to our hospital. Until that point, the ring cell carcinoma, imatinib mesylate. patient had been well with an unremarkable history. Upon 0250-7005/2016 $2.00+.40 1855 ANTICANCER RESEARCH 36: 1855-1860 (2016) Figure 1. Computed tomographic image prior to imatinib mesylate therapy, showing a 21-cm diameter mass in the left upper peritoneal cavity. presentation, the laboratory findings were as follows: Since it seemed unlikely that complete resection would be normal red blood cell count (400×104/mm3; normal range possible because of the large size of the tumor, the patient was 400-552×104/mm3); increased white blood cell count treated with neoadjuvant therapy of imatinib mesylate (400 (14.4×103 /mm3; normal range 3.6-9.6×103/mm3); normal mg/day) for 5 months. After treatment, a CT scan confirmed a platelet count (33.6×104/mm3; normal range 14.8-33.9×104 partial response, with a decrease in tumor dimensions to /mm3); low total protein (6.4 g/dl; normal range 6.7-8.1 9.1×8.3×7.5 cm, without any evidence of metastases (Figure g/dl), low albumin (3.5 g/dl; normal range 3.9-4.9 g/dl); 3). The patient then underwent a total gastrectomy and high lactate dehydrogenase (314 U/l; normal range 119-229 regional lymph-node dissection with distal pancreatectomy U/l); and high C-reactive protein (10.5 mg/dl; normal value, and splenectomy. Intraoperatively, there was no peritoneal <0.30 mg/dl). However, levels of alanine aminotransferase, dissemination and a complete resection was performed by aspartate aminotransferase, total bilirubin, and serum partial resection of the diaphragm because of tumor invasion. creatinine were within normal limits, as were serum Gross examination of the resected specimen showed a well- carcinoembryonic antigen and cancer antigen 19-9. The circumscribed, elevated lesion in the posterior wall of the patient was subsequently admitted to our hospital fornix (Figure 4, arrow) and a depressed lesion measuring complaining of right epigastric pain. 9.0×7.5 cm (Figure 4, arrowhead). Pathological examination Abdominal contrast-enhanced computed tomography (CT) confirmed the diagnosis of high risk GIST for the elevated showed a large, well-defined mass measuring 21×20×14 cm, lesion and SRCC for the depressed lesion, which had invaded with a heterogeneous component occupying the left upper the muscularis propria with one lymph node metastasis. peritoneal cavity, compressing the liver and pancreas (Figure During the postoperative course, the patient developed a 1). Esophagogastroduodenoscopy (EGD) revealed a large minor pancreatic fistula that was treated conservatively using elevated lesion with a deep central ulcer in the upper body tube drainage. In addition, the patient has been receiving (Figure 2A) and a depressed lesion with an indistinct margin postoperative chemotherapy with oral fluoropyrimidine (S- on the lower gastric body near the lesser curvature (Figure 1) without evidence of disease recurrence for 4 months after 2B). Histopathological analysis of an endoscopic biopsy surgery. sample from the large elevated lesion revealed GIST, whereas a biopsy sample from the depressed lesion revealed Discussion signet-ring cell carcinoma (SRCC). There was no evidence of metastatic lesions in other organs. We made a clinical Herein we describe a rare case of a patient with synchronous diagnosis of synchronous large GIST and adenocarcinoma in development of adenocarcinoma and GIST in the stomach the stomach. treated by radical resection following neoadjuvant imatinib 1856 Namikawa et al: GIST with Gastric Cancer Figure 2. Esophagogastroduodenoscopy prior to imatinib mesylate therapy, showing gastrointestinal stromal tumor (A) and adenocarcinoma (B) in the stomach. Figure 3. Computed tomographic image after 5 months of neoadjuvant imatinib mesylate therapy, showing a marked decrease in the size of the tumor. Figure 4. Macroscopic appearance of the resected specimen showing the gastrointestinal tumor (arrow) and the adenocarcinoma (arrowheads). 1857 ANTICANCER RESEARCH 36: 1855-1860 (2016) mesylate, administered because of the large size of the tumor. A search of the English language literature published between 2000 and 2016 was conducted using the Medline and PubMed databases for articles on the synchronous occurrence of GIST in the stomach and primary gastric adenocarcinoma with the key words “gastrointestinal stromal tumor”, “adenocarcinoma”, and “treatment”. Data on age, gender, tumor location, tumor size, depth of invasion, histological type, staging, treatment, and outcome for each ; se, serosa; si, invasion of adjacent ; se, serosa; si, invasion patient were obtained. The clinicopathological features of the 15 previously reported cases (2-13) and the present case are listed in Table I. The median age of patients was 70 years (range=52-80 years) and there was a male predominance, with a male to female ratio of 11:5. muscularis propria GIST lesions in the upper one-third of the stomach were reported in five cases, four patients had lesions in the middle one-third of the stomach, and three had lesions in the lower osa; mp, one-third of the stomach. The median tumor size for GIST was 1.4 cm (range=0.3-21 cm), and this was smaller than the median tumor size of the gastric adenocarcinoma (4.9 cm; range=1.0-10.2 cm). Only three patients had a larger
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