Carcinoid liver cancer

We report a rare case of gastric collision tumor composed of moderately differentiated tubular adenocarcinoma and carcinoid in an 84-year-old woman. On endoscopic examination, an invasive tumor was noted at the cardia of the stomach, and a pathologic examination of the biopsy specimen revealed adenocarcinoma. After total gastrectomy, a thorough histopathologic examination of the resected tumor revealed the concurrent presence of moderately differentiated adenocarcinoma and a typical carcinoid tumor, which had a colliding pattern of tissue proliferation. There was no intermixing or transition area between the 2 components. The final pathologic diagnosis was collision tumor of the adenocarcinoma and carcinoid tumor. The presence of either tumor individually would not be especially noteworthy, but this collision-type tumor of both histopathologic types in the stomach is, to our knowledge, only the sixth such case in the literature.

(Arch Pathol Lab Med. 2005;129:407-409)

Adenocarcinoma is the most common malignant gastric neoplasm, whereas a gastric carcinoid is relatively uncommon, and the coexistence of adenocarcinoma and a typical carcinoid tumor is rare. For such lesions, the tissue morphologic features have been distinguished according to the patterns found in the coexisting components. In the case of an endocrine component, 4 distinct tissue types have been recognized: mixed endocrine and nonendocrine tumor, composite glandular-endocrine cell carcinoma, collision tumor, and amphicrine tumor.1 Furthermore, the first group of mixed endocrine and nonendocrine tumors has been further classified into epithelial tumors, carcinoma with interspersed endocrine cells, and carcinoid with interspersed nonendocrine epithelial cells. Among these groups, composite glandular-endocrine cell carcinoma, collision tumor, and amphicrine tumor have been reported rarely in the stomach, with collision tumor being extremely rare.- Herein, we describe a case with features of adenocarcinoma colliding with a typical carcinoid component.

REPORT OF A case

An 84-year-old Japanese woman with a history of hypertension and complaints of melena and rapid weight loss (10 kg in 3 months) was admitted to the Division of Digestive Surgery, Department of Surgery, Nihon University Itabashi Hospital, Tokyo, Japan, in October 2001. On admission, marked anemia was noted, and her red blood cell count was 1.47 ?? 10^sup 6^/??L. Blood transfusion was started immediately. Other than anemia, the results of a biochemical analysis of her blood and urine were within reference ranges. The carcinoembryonic antigen tumor marker was within the normal limit (2.5 ng/mL; reference range, 0-5.0 ng/ mL), whereas the CA 19-9 marker was 2-fold higher than the normal titer value (94 U/mL; reference range, 0-40 U/mL). Although physical examination did not provide additional information, further endoscopie exploration regarding the cause of the anemia revealed a type 3 ulcer in the cardia of the stomach. CoIonic endoscopy revealed multiple diverticula in the ascending, descending, and sigmoid regions of the colon. Other than the lesion in the stomach, computed tomography and ultrasound sonography revealed no other growths. A gastric biopsy specimen taken from the gastric ulcerative lesion was diagnosed to be adenocarcinoma.

Surgery was the choice of treatment, and the patient underwent total gastrectomy with Roux-en-Y anastomosis. Postoperative recovery was uneventful in the first week. In the second week, she complained of abdominal distension after meals. Stenosis of the anastomosis site was subsequently diagnosed on the third postoperative week after gastroendoscopy, which was dilated by balloon insertion. On the 38th postoperative day, she was discharged from the hospital, and her recovery has been uneventful during a follow-up period of 2 years 9 months.

PATHOLOGIC FINDINGS

Macroscopically, the gastric cardia showed a Borrmann type 3 ulcer with a blunt edge that measured 6 ?? 4 cm (Figure 1). The cut surface (Figure 2) showed a yellowish white tumor at the base and surrounding area of the ulcer, with invasion up to the subserosa. Along with the stomach specimen, 27 resected lymph nodes were submitted.

Microscopically, routine hematoxylin-eosin-stained sections from the tumor showed 2 different types of tissue proliferation. One was moderately differentiated adenocarcinoma, mainly composed of tubules with an occasional papillary pattern and mucinous deposit. The other component was nonadenocarcinoma; it was composed of relatively smaller tumor cells with granular cytoplasm, centrally located nuclei, and an indistinct cytoplasmic border. A trabecular, solid, or sheetlike pattern of tissue proliferation was also noted. The cytoplasmic granules showed argyrophilia on Grimelius staining. On immunohistochemical analysis, a positive response was noted for synaptophysin (DakoCytomation, Glostrup, Denmark) and chromogranin A (DakoCytomation). Accordingly, this component of the tumor was diagnosed as a typical carcinoid tumor. No intermingling or merging of tissue components was noted at the interface of the growth. We diagnosed it as a collision tumor composed of adenocarcinoma and a carcinoid tumor of the stomach (Figures 3 and 4). Both components of the tumor tissue invaded the subserosal layer. Lymphatic permeation by the adenocarcinoma was noted, but there was no vascular invasion. The carcinoid component was negative for both lymphatic and vascular permeations. Metastatic adenocarcinoma was found in the subserosal lymph nodes.

COMMENT

In the present case, the concurrent presence of adenocarcinoma and a typical carcinoid tumor was found in a gastric tumor. In general, a carcinoid tumor of the stomach is rare and constitutes approximately 2% of all gastrointestinal carcinoid tumors.3 The prevalence of a gastrointestinal carcinoid tumor based on the original site differs in Japan and Western countries.4 In Japan, the involvement of the rectum (36.2%), stomach (27.3%), or duodenum (14.9%) as the original site of a gastrointestinal carcinoid is much more frequent than that of the small intestine (3.2%) or appendix (6.6%).5 In contrast, in Europe and the United States, the involvement of the small intestine (36%), appendix (26%>), or rectum (17%) is more common than that of the stomach (4%) or duodenum (3%).3 Only the rectum is commonly involved as the original site of a gastrointestinal carcinoid tumor in both Japan and Western countries.

To our knowledge, there are 32 cases of gastric collision tumor composed of epithelial and nonepithelial malignant neoplasm reported in the literature. A summary of those 32 cases showed a male-female ratio of 2.5:1 and an average age of incidence of 61 years (range, 42-80 years). Most tumors were found in the body of the stomach. In those cases, a simultaneous incidence of adenocarcinoma and malignant lymphoma was the most frequent finding. There were only 5 cases of adenocarcinoma and carcinoid turnor.6-10 The Table gives the details of these 5 cases and our case. The age and sex incidence and the prognosis of these tumors appeared to be similar to those of other common gastric carcinomas. Our case is the sixth instance of collision tumor of adenocarcinoma and the carcinoid in the stomach and is the third such case reported in Japan.

It is noteworthy that the prevalence of gastric cancer in Japan is much higher than that of Europe or the United States. Pathogenic factors such as diet, genetics, and infection by an oncogene or with Hdicobacter pylori may contribute to the development of gastric adenocarcinoma. In addition, endocrine cell hyperplasia associated with pernicious anemia or longstanding gastric atrophy may be a sporadic or secondary contributing factor for a gastric carcinoid tumor. It has been reported that most patients with pernicious anemia develop hypergastrinemia due to proliferation of the endocrine cells.1 However, in our case, pernicious anemia or endocrine-like cell hyperplasia was not seen, and no serum gastrin value was estimated. Usually, it is not easy to morphologically distinguish a collisiontype from a composite-type tumor. Yamashina and Flinner10 reported a case where the 2 different tissue components had grown on one another, designating it a collision tumor. In the present case, the tissue components apparently grew from opposite sides with a readily identifiable line of interface. It has been reported that metastasis from a composite tumor shows both of the tissue constituents, whereas those from a collision tumor show only a single tissue component.1 Our case was compatible with such a finding, since the metastatic lymph nodes showed adenocarcinoma alone.