Case Report
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2020; 26(42): 6689-6697
Published online Nov 14, 2020. doi: 10.3748/wjg.v26.i42.6689
Case series of three patients with hereditary diffuse gastric cancer in a single family: Three case reports and review of literature
Masahiro Hirakawa, Kohichi Takada, Masanori Sato, Chisa Fujita, Naotaka Hayasaka, Takayuki Nobuoka, Shintaro Sugita, Aki Ishikawa, Miyako Mizukami, Hiroyuki Ohnuma, Kazuyuki Murase, Koji Miyanishi, Masayoshi Kobune, Ichiro Takemasa, Tadashi Hasegawa, Akihiro Sakurai, Junji Kato
Masahiro Hirakawa, Kohichi Takada, Masanori Sato, Chisa Fujita, Naotaka Hayasaka, Hiroyuki Ohnuma, Kazuyuki Murase, Koji Miyanishi, Junji Kato, Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan
Masahiro Hirakawa, Department of Gastroenterology, National Hospital Organization Hokkaido Cancer Center, Sapporo 003-0804, Hokkaido, Japan
Takayuki Nobuoka, Ichiro Takemasa, Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan
Shintaro Sugita, Tadashi Hasegawa, Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan
Aki Ishikawa, Miyako Mizukami, Akihiro Sakurai, Department of Medical Genetics, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan
Masayoshi Kobune, Department of Hematology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan
Author contributions: Hirakawa M, Takada K, Sato M, Fujita C, Hayasaka N, Ohnuma H, Murase K, Miyanishi K, Kobune M and Kato J were the patients’ physicians, reviewed the literature and contributed to manuscript drafting; Nobuoka T and Takemasa I were the patients’ surgeons, reviewed the literature and contributed to manuscript drafting; Sugita S and Hasegawa T performed the pathological examination; Ishikawa A, Mizukami M and Sakurai A performed genetic counselling, genetic testing and contributed to manuscript drafting; all authors issued final approval for the version to be submitted.
Informed consent statement: The patients provided informed written consent for all aspects of care described in this manuscript.
Conflict-of-interest statement: The authors have no conflicts to declare.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Masahiro Hirakawa, MD, PhD, Doctor, Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1 West 17, Chuo-ku, Sapporo 060-8556, Hokkaido, Japan. mhirakawa@sapmed.ac.jp
Received: August 28, 2020
Peer-review started: August 28, 2020
First decision: September 30, 2020
Revised: October 11, 2020
Accepted: October 26, 2020
Article in press: October 26, 2020
Published online: November 14, 2020
Processing time: 76 Days and 15.1 Hours
Abstract
BACKGROUND

Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome often associated with germline mutations in the CDH1 gene. However, the frequency of CDH1 mutations is low in patients with HDGC in East Asian countries. Herein, we report three cases of HDGC harboring a missense CDH1 variant, c.1679C>G, from a single Japanese family.

CASE SUMMARY

A 26-year-old female (Case 1) and a 51-year-old male (father of Case 1), who had a strong family history of gastric cancer, were diagnosed with advanced diffuse gastric cancer. After genetic counselling, a 25-year-old younger brother of Case 1 underwent surveillance esophagogastroduodenoscopy that detected small signet ring cell carcinoma foci as multiple pale lesions in the gastric mucosa. Genetic analysis revealed a CDH1 c.1679C>G variant in all three patients.

CONCLUSION

It is important for individuals suspected of having HDGC to be actively offered genetics evaluation. This report will contribute to an increased awareness of HDGC.

Keywords: Hereditary diffuse gastric cancer; Signet ring cell carcinoma; CDH1; E-cadherin; Endoscopic findings; Case report

Core Tip: Hereditary diffuse gastric cancer (HDGC) has rarely been reported in East Asian countries. We report a Japanese HDGC family with a missense CDH1 variant, c.1679C>G (p.T560R). We clearly detected early signet ring cell carcinoma foci by esophagogastroduodenoscopy with white light imaging, non-magnifying narrow band imaging (NBI) and magnifying NBI. In this family, active genetics evaluation and intensive endoscopic surveillance resulted in early diagnosis and treatment of HDGC.