Clinical quiz. Gastric adenocarcinoma.

Abstract

A 16-year-old African-American boy was referred to the Pediatric Gastroenterology Service at the Children's Hospital of Michigan, Wayne State University, Detroit, for evaluation of asymptomatic anemia (hemoglobin 8.1 g/dl and mean corpuscular volume 64/μl). He had no history of abdominal pain, vomiting, heartburn, weight loss or dyspepsia. Physical examination was unremarkable except for guaiac-positive stools. He underwent esophagogastroduodenoscopy (EGD). The endoscopic findings in the stomach are shown in Figure 1. A CLO test for Helicobacter pylori was positive. Histopathology of the gastric mucosal biopsy specimen is shown in Figure 2. The esophagus and duodenum were normal on endoscopy and histology. Pancolonoscopy with surveillance biopsy was then performed, and results were entirely normal. What is the most likely diagnosis? Peutz-Jeghers syndrome Familial polyposis coli/Gardner's syndrome Gastric adenocarcinoma Gastric lymphoma Gastric hyperplastic polyps FIG. 1FIG. 2ANSWER: See page 629. Answer: Gastric adenocarcinoma. Analysis of the gastric mucosal specimen (Fig. 2) revealed high-grade dysplasia with full-thickness stratification and nuclear atypia of surface and glandular epithelium, suggestive of a malignant process. The patient's family history was significant for the deaths of his identical twin brother in the previous month and his mother 1 year earlier from metastatic gastric adenocarcinomas which manifested as large gastric ulcers. He was living with his grandparents and a 12-year-old half-brother. Initial abdominal computed tomographic (CT) examination revealed multiple gastric polyps and diffuse thickening of the stomach wall, but no metastases. Treatment of the H. pylori using triple therapy with lansoprazole, amoxicillin, and clarithromycin for 2 weeks was found to be unsuccessful during follow-up EGD. The patient and his family refused gastrectomy. He was admitted 5 months later with a short history of back and abdominal pain, vomiting, jaundice, and hepatomegaly. A second abdominal CT scan revealed large gastric masses, interval development of multiple lesions in the liver and porta hepatis, and vertebral and paravertebral masses, consistent with metastatic disease. A CT-guided needle biopsy of a right paravertebral mass confirmed the presence of metastatic gastric adenocarcinoma (Fig. 3). He died 2 weeks later. The family refused autopsy and surveillance testing of other family members. Blood samples and gastric biopsy tissue sent to the Familial Gastrointestinal Cancer Registry (Toronto, Canada) for APC germline mutation studies tested negative.FigureComment: Although H. pylori has been associated with the occurrence of gastric mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas, we could not prove any such association in this case. Familial genetic mechanisms seem to play a role in certain occurrences of gastric adenocarcinoma (1), although it is much less recognized than in colorectal cancer. The APC gene responsible for familial adenomatous polyposis is mutated in some cases of gastric adenocarcinoma (2). Familial occurrence of gastric cancer is seen in 10% to 15% of patients. Recently, a gene responsible for early-onset, poorly differentiated, high-grade, diffuse gastric cancer has been identified in a large kindred in New Zealand. The gene has been shown to be strongly linked to markers flanking the gene for the calcium-dependent, cell-adhesion protein E-cadherin. Underexpression of E-cadherin is associated with aggressive carcinomas. This may be the molecular basis of familial gastric cancer (3).