Endoscopic surveillance finds unsuspected carcinomas in predisposed individuals

Last Updated: 2019-04-10

By Reuters Staff

NEW YORK (Reuters Health) - Endoscopic surveillance can identify unsuspected signet-ring-cell carcinoma in individuals predisposed to hereditary diffuse gastric cancer (HDGC) by virtue of pathogenic variants in CDH1, researchers report.

Pathogenic germline variants in the epithelial cadherin gene (CDH1) result in uncontrolled cell growth and division and an increased risk of specific cancers, including diffuse gastric cancer, lobular breast cancer and signet-ring-cell colon cancer.

The lifetime risk for diffuse gastric cancer (DGC) in patients with such variants is estimated to be 40% to 80%, but the optimal clinical management of patients with pathogenic CDH1 germline variants who lack a family history of DGC remains unclear.

Dr. Elena M. Stoffel of the University of Michigan, Ann Arbor, and colleagues investigated the outcomes of endoscopic surveillance and prophylactic gastrectomy among 20 asymptomatic CDH1 carriers with and without a family history of DGC.

None of these individuals had diagnostic findings visible during endoscopic examination, but histopathological review of pan-gastric endoscopic biopsies identified abnormal histology consistent with signet-ring-cell carcinoma (SRCC) in eight of the 20 individuals (40%).

Four of the eight individuals with abnormal endoscopic biopsies had a first-degree relative with DGC, and two additional individuals had a family history of at least one DGC in a second-degree relative, the researchers report in Gastroenterology, online March 29.

Five of the six individuals with abnormal biopsies who proceeded to total gastrectomy had SRCC identified, but one had no SRCC detected on the gastrectomy specimen. Two individuals with abnormal biopsies declined surgery.

Ten of the 12 individuals with negative biopsies chose to undergo prophylactic gastrectomy, and four of these had SRCC identified on gastrectomy specimens. All but one of these cancers were noninvasive.

Overall, fewer than half of the individuals with SRCC (five of 12) had a first-degree relative with gastric cancer.

"While some questions remain unanswered, it is clear from our and previous studies that the prevalence of CDH1 mutations is higher than appreciated based on family history of DGC alone," the researchers conclude. "Furthermore, a 'normal' endoscopy and absence of a family history cannot exclude risk for DGC."

"Until more data are available to quantify risks of DGC, the option of prophylactic gastrectomy should be discussed with patients with germline pathogenic CDH1 variants, even in the absence of a family history of DGC," they conclude.

Dr. Stoffel did not respond to a request for comments.

SOURCE: https://bit.ly/2UdbOze

Gastroenterology 2019.