Role of pathology in the identification of hereditary diffuse gastric cancer: report of a Portuguese family

Mutations in E-cadherin gene are the underlying genetic defect in approximately one-third of the hereditary diffuse gastric cancer (HDGC) families described to date. Positive family history of diffuse gastric cancer and early age of onset of gastric tumours are the clinical criteria currently used to qualify for HDGC. In the present study, we describe a Portuguese family with HDGC that was selected for CDH1 mutation screening after histological observation of the gastrectomy specimen of one member, who died at the age of 23 years from widely invasive diffuse gastric carcinoma. The detection in the surgical specimen of tiny foci of intramucosal diffuse carcinoma as well as in situ carcinoma lesions and pagetoid spread of signet ring cells raised the hypothesis of HDGC, which was confirmed by pedigree analysis of the family and detection of CDH1 germline mutation. We conclude that there are morphological hints that may help in the identification of HDGC.