Hereditary diffuse gastric cancer with a CDH1 mutation and a separate gallbladder cancer

What happened, in summary

A 67-year-old woman was being evaluated for a separate gallbladder cancer when endoscopy found several flat white lesions in the lower stomach. Biopsies confirmed signet-ring cell carcinoma. Her family history was notable for gastric cancer in her father and older brother, both of whom died before age 40, raising concern for hereditary diffuse gastric cancer.

She underwent total gastrectomy for the gastric cancer while also receiving separate surgery for the gallbladder cancer. Examination of the stomach found 22 malignant lesions scattered throughout the stomach, far more than had been visible on endoscopy. Twenty-one were signet-ring cell carcinomas and one was a poorly differentiated adenocarcinoma. All of the gastric lesions were limited to the inner stomach lining, with no regional lymph-node involvement. The gastric cancer was classified as Stage I.

Because of the pattern of multiple diffuse gastric cancers and her family history, she received genetic counseling and germline testing. Testing identified a pathogenic CDH1 mutation, supporting the diagnosis of hereditary diffuse gastric cancer. The gallbladder cancer was a separate primary cancer rather than spread from the stomach. The combination of multifocal signet-ring cancers and the pathogenic CDH1 finding established a hereditary gastric-cancer syndrome that also has implications for ongoing cancer surveillance.