Hereditary Diffuse Gastric Cancer With Poorly Differentiated Gallbladder Adenocarcinoma: A Case Report Suggesting Carcinogenesis in the Stomach and Gallbladder Caused by a Pathogenic Germline Variant in CDH1 .
Masato Hayashi, Naoto Kubota, Makoto Abe et al.
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Case in brief
A 67-year-old woman was referred for management of gallbladder cancer after cholecystectomy for progressive gallbladder wall thickening. Pathology showed poorly differentiated adenocarcinoma invading the subserosa, with reduced E-cadherin expression. Her father and brother had died of gastric cancer at young ages, prompting gastric endoscopy; biopsies of multiple faded mucosal lesions showed signet-ring cell carcinoma. Gastrectomy and gallbladder bed resection revealed 22 gastric malignancies, predominantly pT1a signet-ring cell carcinomas, with variable or absent E-cadherin expression. Germline testing identified a pathogenic CDH1 frameshift variant.
What made this case unusual
The case combined hereditary diffuse gastric cancer with a primary, poorly differentiated gallbladder adenocarcinoma, both in the setting of a pathogenic germline CDH1 variant. The authors suggest a possible contribution of the variant to gallbladder carcinogenesis.
Diagnostic / clinical pearl
Poorly differentiated gallbladder adenocarcinoma with reduced E-cadherin expression, particularly alongside a strong family history of gastric cancer, may warrant evaluation for hereditary diffuse gastric cancer.