Hereditary diffuse gastric cancer with carcinogenesis from ectopic gastric mucosa in the duodenum

Sep 22, 2026

Uploaded by Kyle

A 43-year-old man with a family history of gastric cancer had signet-ring cell carcinoma treated twice by endoscopic submucosal dissection (ESD). After recurrent mucosal lesions, immunohistochemistry showed reduced E-cadherin and CDH1 testing identified the R732Q missense mutation. Total gastrectomy revealed 22 intramucosal signet-ring cell carcinoma foci. The most distal carcinoma was in the duodenal bulb and was consistent with origin from ectopic gastric mucosa, suggesting CDH1-related carcinogenesis beyond the stomach. The authors recommend screening for ectopic gastric mucosa in CDH1 mutation carriers.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Case report

Background and diagnosis

CDH1 mutation and treatment

Surgical findings and ectopic mucosa origin

Implications for screening

Clinical Journal of Gastroenterology (2026) 19:388–394 [https://doi.org/10.1007/s12328-025-02279-9](https://doi.org/10.1007/s12328-025-02279-9) CASE REPORT Hereditary diffuse gastric cancer with carcinogenesis from ectopic gastric mucosa in the duodenum Kazuki Horiuchi1 · Yusuke Ishibashi2 · Akira Tomioka3 · Kazuyuki Narimatsu3 · Hironori Tsujimoto4 · Ryota Hokari3 · Kei Kato5 Received: 24 September 2025 / Accepted: 26 December 2025 / Published online: 27 January 2026 © The Author(s) 2026, modified publication 2026 Abstract A 43-year-old man with a family history of gastric cancer had undergone endoscopic submucosal dissection (ESD) fora signet-ring cell carcinoma (SRCC) lesion. Five years later, a recurrent SRCC lesion was treated with a second ESD. Two months later, multiple recurrent SRCC lesions were again detected. Immunohistochemical staining revealed reduced E-cadherin expression. Genetic testing for CDH1 identified an R732Q missense mutation. The patient subsequently underwent total gastrectomy, which identified 22 intramucosal SRCC lesions. Notably, the most distal carcinoma was located in the duodenal bulb and appeared to arise from mucosa containing gastric fundic glands, gastric foveolar epithelium, CD10-positive cells, MUC2-positive cells, and Brunner’s glands, suggesting origin from ectopic gastric mucosa in the duodenum. To our knowledge, this is the first reported case of SRCC arising from ectopic gastric mucosa in patients with hereditary diffuse gastric cancer. Screening for ectopic gastric mucosa may be warranted in patients with CDH1 mutations. Keywords Hereditary diffuse gastric cancer · R732Q · Ectopic gastric mucosa Introduction Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant inherited disease caused by CDH1 mutations, leading to diffuse gastric cancer (DGC) due to abnormal expression of E-cadherin, a key cell adhesion protein [1] . According to the International Gastric Cancer Linkage Consortium (IGCLC) guidelines [2], total gastrectomy is the only curative treatment following a definitive diagnosis, as 􀀍 Kazuki Horiuchi [hkazuki@ndmc.ac.jp](hkazuki@ndmc.ac.jp) 1 Department of Internal Medicine, Japan Self-Defense Force Iruma Hospital, 2-1-4, Koyodai, Iruma, Saitama 358-0001, Japan 2 Department of Surgery, Japan Self-Defense Force Iruma Hospital, 2-1-4, Koyodai, Iruma, Saitama 358-0001, Japan 3 Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan 4 Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan 5 Department of Pathology, Japan Self-Defense Force Iruma Hospital, 2-1-4, Koyodai, Iruma, Saitama 358-0001, Japan complete removal of the gastric mucosa is essential. Here, we report a case in which a patient underwent total gastrectomy after the identification of a CDH1 mutation, with additional consideration of carcinogenesis arising from ectopic gastric mucosa in the duodenum. Case report A 43-year-old man underwent endoscopic submucosal dissection (ESD) after a 0–IIc lesion was incidentally identified on the anterior wall of the lower gastric body during esophagogastroduodenoscopy (EGD) at a routine medical checkup. Histological examination revealed signet-ring cell carcinoma (SRCC) confined to the mucosa. The patient underwent EGD follow-up every six months and showed no recurrence after ESD. At the age of 48, the patient began follow-up at our hospital. Initial EGD revealed a 0–IIclesion in the fornix, which was biopsied and diagnosed as SRCC. The patient underwent ESD again, and pathological examination confirmed intramucosal carcinoma. Two months later, follow-up EGD revealed four whitish areas in the gastric antrum (Fig. 1), all of which were diagnosed as SRCC, and showing reduced E-cadherin expression and no Fig. 1 Representative images of esophagogastroduodenoscopy. Flat, whitish areas were observed on the anterior wall a, pos

FAQs

What genetic change was identified in this case of hereditary diffuse gastric cancer?

Genetic testing for CDH1 identified an R732Q missense mutation.

How were recurrent signet-ring cell carcinoma lesions managed before surgery?

The patient underwent endoscopic submucosal dissection (ESD) twice for recurrent mucosal signet-ring cell carcinoma lesions, followed by surveillance endoscopy.

What evidence suggested carcinogenesis arose from ectopic gastric mucosa in the duodenum?

The most distal carcinoma was located in the duodenal bulb and the surrounding mucosa showed gastric-type components including gastric fundic glands, gastric foveolar epithelium, CD10-positive cells, MUC2-positive cells, and Brunner’s glands.

Sep 22, 2026

Uploaded by Kyle