Hereditary diffuse gastric cancer presenting in a young asymptomatic patient: an uncommon entity with an ominous prognosis.

Hereditary gastric cancer is a relatively uncommon entity comprising approximately 1-3% of all gastric cancers. Gastric adenocarcinoma is typically a sporadic disease with two histologic subtypes, intestinal and diffuse. The intestinal type is highly associated with Helicobacter pylori (HP) while the diffuse type is more common in younger patients, and those with blood group type A. Recently, germline mutations of the oncogene CDH1 that encodes E-cadherin, a tumor suppressing protein, were discovered in a few families with hereditary diffuse gastric carcinoma (HDGC); this condition has an autosomal dominant pattern of inheritance with variable penetrance. An asymptomatic 36-year-old gentleman was referred to WHMC after a screening esophagogastroduodenoscopy (EGD) revealed an atrophic appearing region in the antrum that was a biopsy-proven signet-ring cell adenocarcinoma. He had a strong family history of gastric cancer consistent with an autosomal dominant pattern of inheritance. A repeat EGD at WHMC revealed a 4-5 mm slightly raised plaque-like lesion in the antrum, and multiple gastric biopsies of uninvolved mucosa demonstrated gastritis and H pylori. An endoscopic ultrasound revealed no involvement of the muscularis propria or regional lymphadenopathy (T1N0). A laparoscopic total gastrectomy with esophagojejunostomy was then performed without complication. Pathology showed multifocal invasive gastric carcinoma, signet-ring cell type, confined to the submucosa (T1). Special stains for E-cadherin confirmed a germ-line mutation of the CDH1 gene. He is currently awaiting genetic counseling. The optimal management of HDGC has been controversial. Recent studies have shown that prophylactically resected stomachs from CDH1 mutation carriers that had clinically undetectable disease with endoscopy carried multifocal intramucosal signet-ring cell cancer. Patients with an autosomal dominant pattern of diffuse type gastric cancer should undergo genetic testing for a CDH1 germ-line mutation, and if present, should prompt consideration for a prophylactic total gastrectomy.

CPT Jeffery J. Blonsky (ACP Associate), LTC Kevin T. Watkins, MAJ Steven P. Bowers, and MAJ Alejandro Pruitt (ACP Member). Departments of Internal Medicine and Surgery, Wilford Hall Medical Center (WHMC), Lackland AFB, San Antonio, TX.