S3703 A Case of Hereditary Diffuse Gastric Cancer

Abstract

Introduction: Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant disorder associated with pathogenic germline variants in the cadherin 1 (CDH1) or alpha-1 catenin (CTNNA1) genes. Carriers have an 80% risk of developing stomach cancer, at an average age of 38, and 60% lifetime risk of developing lobular breast cancer. This is a case of a middle-aged female diagnosed with CDH1+ HDGC. Case Description/Methods: An asymptomatic 50-year-old Bangladeshi female presented for surveillance colonoscopy given a strong family history of colon cancer in three siblings, mother and uncle and stomach cancer in her mother. She had a normal upper endoscopy three years earlier for indication of heartburn. She proceeded with colonoscopy which showed two tubular adenomas measuring 7-8 mm. Due to concern of a hereditary syndrome, she was referred to a genetics counselor and an Ambry Colonext Panel with RNA Analysis was conducted. Results were positive for pathogenic heterozygous c.1137G >A mutation in the CDH1 gene raising concern for HDGC. At the time, she opted for surveillance instead of prophylactic gastrectomy. A follow up upper endoscopy showed a few, minute pale regions on close inspection, but no masses, ulcerations or other features suggestive of malignancy. Per Cambridge protocol, 34 biopsies were collected and one gastric body biopsy returned positive for gastric adenocarcinoma with signet ring cell features and weak E-Cadherin expression. Cross sectional imaging was negative for metastatic disease. She met with oncology and surgery teams and underwent laparotomy with total gastrectomy and Roux-en-Y esophagojejunostomy. Gastrectomy biopsy confirmed a single microscopic focus of diffuse adenocarcinoma. Discussion: Diagnosis of HDGC-associated signet ring cancers is especially difficult because they are only visible on direct mucosal evaluation late in the disease process. Genetic testing is recommended for those meeting family or individual criteria. Prophylactic gastrectomy, as early as age 20, is recommended for pathogenic mutation carriers with an appropriate pedigree. Those denying surgery can be offered annual endoscopy with the understanding that frequent surveillance has not been proven to be effective in early gastric cancer detection in HDGC. During endoscopy, any visible lesion should be biopsied and a minimum of 30 biopsies are recommended to include all five anatomic gastric zones. H. pylori should be screened for and treated. Referral to a breast surgeon is also recommended.