Prophylactic Gastrectomy in Hereditary Diffuse Gastric Cancer

Abstract

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. It is classified as intestinal and diffuse. Only 1-3% of all cases are inherited and include hereditary diffuse gastric cancer (HDGC). It has an autosomal dominant inheritance with poor prognosis. The risk for developing gastric cancer in people with E. cadherin1 encoding gene (CDH1) mutations is estimated to be 70% for men and 83% for women at an average age of 38. We present a case of a patient with HDGC, who underwent prophylactic gastrectomy with a prior negative EGD. A 38-year-old woman with CDH1 mutation and a family history of colon, gastric, and breast malignancies in first and second-degree relatives, presented for endoscopic surveillance of gastric cancer. EGD was unremarkable and she was scheduled for a 1-year follow-up. One year later, after further evaluation, she was recommended to undergo prophylactic gastrectomy. She underwent an exploratory laparotomy with subtotal gastrectomy and jejunal pouch creation. Biopsy revealed poorly differentiated adenocarcinoma of the stomach, penetrating the serosa, stage T4aN1M0. Due to family history, CDH1 mutation and a personal history of gastric cancer, the patient was diagnosed with HDGC. She was started on chemotherapy with future plans for radiation. Patients with GC are usually asymptomatic or have nonspecific symptoms. Breast cancer might be the only presenting pathology because of its association with CDH1. A gastric tumor may be the initial presentation of HDGC syndrome in CDH1 positive individuals without a positive family history. CDH1 gene is found in only 30-50% of all HDGC cases, suggesting a potential for additional gene involvement. Current guidelines recommend prophylactic total gastrectomy without D2 node dissection in all confirmed CDH1 mutation carriers between ages 18-40 years. A baseline endoscopy is indicated prior to gastrectomy to map gastric margins, identify any macroscopic tumors, and to rule out Barrett's esophagus. EGD with mapping biopsies can detect 9% of patients with microscopic foci of adenocarcinoma with one study showing 65%. Women with CDH1 mutations should undergo annual mammogram and should consider breast MRI at age 30, or 5-10 years earlier than the youngest diagnosis in the family. Patients with an incidental finding of CDH1 mutations during multi-genetic testing or those without a family history of HDGC should at least undergo screening EGD and be referred to HDGC specialist.2718_A Figure 1. CK7 stain highlighting tumor cells.2718_B Figure 2. Tumor cells at serosal edge.