ArticleFamilial cancer2026
Endoscopic detection of signet ring cell carcinoma in CDH1 carriers: a 15-year single-centre experience.
Article in Familial cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
CDH1 pathogenic variant carriers are at high lifetime risk of hereditary diffuse gastric cancer (HDGC). Endoscopic surveillance is recommended for individuals who delay risk-reducing total gastrectomy, although detection of signet ring cell carcinoma (SRCC) remains challenging. No Australian cohort has reported real-world endoscopic performance with surgical correlation in this population. We performed a 15-year retrospective cohort study of adult CDH1 carriers undergoing esophagogastroduodenoscopy (EGD) at a tertiary familial cancer centre (2008-2023). Patients presenting with symptomatic invasive gastric cancer at initial endoscopy were excluded. Most EGDs were conducted as preoperative assessments prior to risk-reducing total gastrectomy, with a minority undertaken as longitudinal surveillance. Endoscopic findings, biopsy performance, surgical pathology, and postoperative outcomes were analysed. Eighty-two CDH1 carriers from 31 families underwent 136 EGDs (median 1 per patient). SRCC was detected endoscopically in 38 patients (46.3%), predominantly via random biopsies. Overall sensitivity for SRCC detection was 67.9%, with random biopsies outperforming targeted sampling. Most lesions were identified at the initial EGD. Sixty-nine patients (84.1%) proceeded to total gastrectomy; SRCC was confirmed in 56 (81.2%), with variable tumour burden (1-73 foci). Invasive disease beyond pT1a was uncommon (2.9%). Postoperative complications occurred in 43.5%, most frequently anastomotic strictures requiring dilatation; there were no procedure-related deaths. Although occult SRCC was common, invasive malignancy beyond pT1a was infrequent, suggesting that many intramucosal lesions may have a more indolent course than previously assumed. Detection of SRCC at endoscopy remains challenging; however, these findings support a more individualized, risk-adapted approach to CDH1 management. Longer-term prospective data are required to better define SRCC progression risk and guide decisions regarding surveillance and risk-reducing surgery.
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