Composite Neuroendocrine Carcinoma with Adenocarcinoma of the Stomach Mimicking Double Primary Cancer

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(1)대한외과학회지：제 70 권 제4호 Vol. 70, No. 4, April, 2006. □ Case Report □. Composite Neuroendocrine Carcinoma with Adenocarcinoma of the Stomach Mimicking Double Primary Cancer Department of Surgery, University of Ulsan College of Medicine, Seoul Asan Hospital, Seoul, Departments of 1Surgery, 2 Diagnostic Pathology, 3Diagnostic Radiology and 4Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, Korea. Jin Young Seo, M.D., Myoung Sik Han, M.D.1, Dae Woon Eom, M.D.2, Seung Mun Jung, M.D.3, Byung Kyu Nah, M.D.4, Hyuk Jai Jang, M.D.1, Yong Ho Kim, M.D.1, Jin Ho Kwak, M.D.1, Yong Pil Cho, M.D.1 1 and Youn Baik Choi, M.D.. 원발성 중복 종양의 형태로 나타난 위선암을 동반한 혼합 신경내분비 종양 1. 2. 3. INTRODUCTION. Neuroendocrine carcinoma is occasionally accompanied by adenocarcinoma, but the relationship between these two morphologically distinct tumors is unclear.(1-12) Two hypotheses have arisen regarding the mechanism for the association of adenocarcinoma and neuroendocrine carcinoma: (1) both are derived from a common multipotential epithelial stem cell, the neuroendocrine carcinoma component resulting from differentiation from the adenocarcinoma to the neuroendocrine cell phenotype during tumor progression, (2) adenocarcinoma and neuroendocrine carcinoma arise from a multipotential epithelial stem cell and a primitive neuroendocrine cell, respectively, and they exist next to each other coincidentally.(1) We report a case of the composite neuroendocrine carcinoma with adenocarcinoma of the stomach (mixed exocrine-endocrine carcinoma), in which the preoperative diagnosis was a double primary cancer of the stomach and periampullary area by upper gastrointestinal endoscopy with biopsies and contrast-enhanced axial computed tomographic (CT) scan.. 4. 서진영․한명식 ․엄대운 ․정승문 ․나병규 ․장 1 1 1 1 1 혁재 ․김용호 ․곽진호 ․조용필 ․최윤백. A 67-year-old man presented with a 3-month history for intermittent epigastric pain and postprandial discomfort. Upper gastrointestinal endoscopy and contrast-enhanced axial computed tomographic scan demonstrated two separate tumors of the gastric antrum and the duodenal second portion, suggestive of the preoperative diagnosis of a double primary cancer. Pancreaticoduodenectomy with lymph node dissection was performed, and the microscopic features and immunohistochemical profiles of the resected specimen confirmed the diagnosis of the composite neuroendocrine carcinoma with adenocarcinoma of the stomach (mixed exocrine-endocrine carcinoma). (J Korean Surg Soc 2006; 70:321-324) Key Words: Neuroendocrine tumors, Adenocarcinoma, Stomach 중심 단어: 신경내분비 종양, 선암, 위 ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ. 울산대학교 서울아산병원 외과 및 강릉아산병원 1외과, 2 진단병리과, 3진단방사선과, 4내과. CASE REPORT. A 67-year-old man presented with a 3-month history for intermittent epigastric pain and postprandial discomfort. Laboratory findings showed no abnormalities on urine, peripheral blood, or serum examination. Upper gastrointestinal endoscopy suggested a. 책임저자：조용필, 강원도 강릉시 사천면 방통리 415번지 ꂕ 210-711, 울산대학교 의과대학 강릉아산병원 외과 Tel: 033-610-3229, Fax: 033-641-8120 E-mail: [email protected] 접수일：2005년 7월 26일, 게재승인일：2005년 11월 7일. 321.

(2) 322. 대한외과학회지：제 70 권 제 4 호 2006. ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ. A. B. Fig. 1. Preoperative contrast-enhanced axial CT scan demonstrated (A) a huge, exophytic mass in the prepyloric antrum of the stomach (open arrow) and (B) a 4×3 cm sized, ovoid mass just distal to the ampulla of Vater (white arrow).. huge ulcerofungating and infiltrative lesion in the gastric antrum and an ulcerative lesion in the duodenal second portion. Biopsy from the gastric portion of the tumor revealed adenocarcinoma whereas that from the duodenal portion revealed neuroendocrine carcinoma. Contrast-enhanced axial CT scan demonstrated a huge, exophytic mass in the prepyloric antrum of the stomach and a 4×3 cm sized, ovoid mass just distal to the ampulla of Vater (Fig. 1). Following a diagnosis of a double primary cancer of the stomach and periampullary area, pancreaticoduodenectomy with lymph node dissection was performed. Gross examination of the surgical specimen showed an ulcerofungating tumor, measuring 8.5×7.5×4.5 cm to be present in the antrum of the stomach (Fig. 2). The tumor extended to the serosa with bulging out appearance. A well-demarcated ovoid mass was noted in the peripancreatic area, measuring 4×3×3 cm. The overlying duodenal mucosa was ulcerated, and the tumor involved duodenal wall and pancreatic parenchyma. Microscopically, the gastric tumor was composed of well to moderately differentiated adenocarcinoma (CEA; positive, cytokeratin; strong positive, CD56, chromogranin and synapatophysin; negative) and solid sheets of poorly differentiated neuroendocrine carcinoma (cytokeratin; dot-like focal positive, CD56, chromogranin and synapatophysin; strong positive, CEA; negative) (Fig. 3). The Ki67 labeling index (MIB-1) of the small cell carcinoma-. Fig. 2. The cut surface of the primary tumor of the stomach showed an ulcerofungating, huge tumor with exophytic growth to be present in the gastric antrum.. tous components was higher (24.5%) rather than that of adenocarcinomatous components (8.5%). Intermingled or transitional areas of the two tumor components were noted, supporting the diagnosis of composite neuroendocrine carcinoma with adenocarcinoma (mixed exocrine-endocrine carcinoma), with extension to serosa, no vascular tumor emboli, no lymph nodes metastasis (0/29), and clear resection margins. The microscopic features and immunohistochemical profiles of the peripancreatic mass were similar to those of the neuroendocrine carcinoma of the stomach, confirming the diagnosis of a metastatic tumor of neuroendocrine carcinoma component of.

(3) Jin Young Seo, et al：Composite Neuroendocrine Carcinoma with Adenocarcinoma of the Stomach Mimicking Double Primary Cancer. 323. ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ. A. C. the stomach, with involvement of duodenal wall and pancreatic parenchyma. The postoperative course was uneventful and the patient was discharged without complications. DISCUSSION. It is well known that neuroendocrine carcinomas are occasionally accompanied by adenocarcinomas in the gastrointestinal tract.(1-12) Morphologically, such lesions are classified into two subgroups: compositetype tumors, in which both components appear to be mixed haphazardly,(1-5) and collision-type tumors, which are considered as double tumors with a “side by side” or “one upon another” pattern.(5,6) In this case, the gastric tumor consisted of two different components, one being a well to moderately differentiated adenocarcinomatous area, and the other being a small cell endocrine carcinomatous area composed of a diffuse proliferation of atypical. B Fig. 3. The microscopic features and immunohistochemical profiles of the gastric tumor confirmed the diagnosis of composite neuroendocrine cell carcinoma with adenocarcinoma. (A) The gastric tumor was composed of well to moderately differentiated glandular component and solid sheet of poorly differentiated carcinoma component (×40, hematoxylin and eosin staining). (B) Cytokeratin staining demonstrated diffusely positive in the cytoplasm of the glandular component and focally positive in the solid component with dot-like appearance (×200). (C) Chromogranin and synapatophysin staining showed diffusely positive in the cytoplasm of the solid component, but negative in the glandular component (×200).. round-to-oval cells in a sheet fashion. The tumor cells in the small cell carcinomatous component were immunoreactive to chromogranin and synaptophysin, which indicated that the tumors were neuroendocrine in nature. Furthermore, a histological gradual transition was also observed between the adenocarcinomatous area and the neuroendocrine carcinomatous area. These findings thus indicated the present tumor to be a composite glandular-neuroendocrine carcinoma of the stomach. The microscopic features and immunohistochemical profiles of the peripancreatic mass were similar to those of the neuroendocrine carcinoma of the stomach. Therefore, this should be diagnosed as a metastatic tumor of neuroendocrine carcinoma component of the stomach. Composite glandular-endocrine tumors are rare and are evenly divided between well-differentiated and poorly-differentiated types.(1-5) Composite tumors occur in patients from 32 to 74 years of age and.

(4) 324. 대한외과학회지：제 70 권 제 4 호 2006. ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ. involve the gastric antrum and body to an equal extent. The histogenesis of composite tumors is unclear, but both types of carcinoma may be derived from the same cell, most likely a pluripotent stem cell or an adenocarcinoma precursor cell as opposed to a preexisting neuroectodermal cell.(1-5) In this case, two possible mechanisms might account for the mixed histologic character of the present tumor. A malignant transformation of a common dysplastic epithelial cell could have produced both adenocarcinoma and neuroendocrine carcinoma. Alternatively, a malignant transormation of dysplastic epithelial cells may have resulted in adenocarcinoma, a part of which then further differentiated into neuroendocrine cell component. The preoperative diagnosis of this case was a double primary cancer of the stomach and periampullary area; upper gastrointestinal endoscopy and contrastenhanced axial CT scan demonstrated two separate tumors in the gastric antrum and the duodenal second portion. Furthermore, biopsies from these two separate tumors revealed adenocarcinoma and neuroendocrine carcinoma, respectively. However, the microscopic features and immunohistochemical profiles of the resected specimen confirmed the diagnosis of the composite neuroendocrine carcinoma with adenocarcinoma of the stomach (mixed exocrine-endocrine carcinoma) and a metastatic tumor of neuroendocrine carcinoma component of the stomach in the duodenal area and pancreatic parenchyma. We report a case of the composite neuroendocrine carcinoma with adenocarcinoma of the stomach (mixed exocrine-endocrine carcinoma), in which upper gastrointestinal endoscopy with biopsies and contrastenhanced axial CT scan suggested the diagnosis of a double primary cancer, preoperatively.. REFERENCES 1) Fukui H, Takada M, Chiba T, Kashiwagi R, Sakane M,. 2). 3) 4). 5). 6). 7) 8). 9). 10). 11). 12). Tabata F, et al. Concurrent occurrence of gastric adenocarcinoma and duodenal neuroendocrine cell carcinoma: a composite tumour or collision tumours? Gut 2001;48: 853-6. Roger LW, Murphy RC. Gastric carcinoids and carcino-mas: morphologic correlates of survival. Am J Surg Pathol 1979; 3:195-202. Ulich TR, Kollin M, Lewin KJ. Composite gastric carcinoma. Arch Pathol Lab Med 1988;112:91-3. Levendoglu H, Cox CA, Nadimpalli V. Composite (adenocarcinoid) tumors of the gastrointestinal tract. Dig Dis Sci 1990;35:519-25. Yamashina M, Flinner RA. Concurrent occurrence of adenocarcinoma and carcinoid tumor in the stomach: a composite tumor or collision tumors? Am J Clin Pathol 1985;83: 233-6. Corsi A, Bosman C. Adenocarcinoma and atypical carcinoid: morphological study of a gastric collision-type tumour in the carcinoma-carcinoid spectrum. Ital J Gastroenterol 1995;27:303-8. Lattes R, Grossi C. Carcinoid tumors of the stomach. Cancer 1956;9:698-711. Baudin E, Gigliotti A, Ducreux M, Ropers J, Comoy E, Sabourin JC, et al. Neuron-specific enolase and chromogranin A as markers of neuroendocrine tumours. Br J Cancer 1998; 78:1102-7. Yamamoto J, Abe Y, Nishihara K, Katsumoto F, Takeda S, Abe R, et al. Composite glandular-neuroendocrine carcinoma of the hilar bile duct: report of a case. Surg Today 1998; 28:758-62. Tsujii T, Kambara T, Shimizu K, Tsubaki M, Kamai T, Abe H, et al. Adenocarcinoma with extensive neuroendocrine differentiation arising in an ileal diverticulum: report of a case. Surg Today 2002;32:439-42. Owen NJ, Sohaib SA, Peppercorn PD, Monson JP, Grossman AB, Besser GM, et al. MRI of pancreatic neuroendocrine tumours. Br J Radiol 2001;74:968-73. Kim YH, Oh ST, Jung DH, Yook JH, Kim BS, Park GC. Clinicopathologic characteristics of neuroendocrine tumor of the stomach. J Korean Surg Soc 2000;58:650-5..

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