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Review
. 2020 Nov 14;26(42):6689-6697.
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  1 , Kohichi Takada  1 , Masanori Sato  1 , Chisa Fujita  1 , Naotaka Hayasaka  1 , Takayuki Nobuoka  2 , Shintaro Sugita  3 , Aki Ishikawa  4 , Miyako Mizukami  4 , Hiroyuki Ohnuma  1 , Kazuyuki Murase  1 , Koji Miyanishi  1 , Masayoshi Kobune  5 , Ichiro Takemasa  2 , Tadashi Hasegawa  3 , Akihiro Sakurai  4 , Junji Kato  1
Affiliations
Review

Case series of three patients with hereditary diffuse gastric cancer in a single family: Three case reports and review of literature

Masahiro Hirakawa et al. World J Gastroenterol. .

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

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Conflict of interest statement

Conflict-of-interest statement: The authors have no conflicts to declare.

Figures

Figure 1
Figure 1
Pedigree of this family. Several individuals with gastric cancer were confirmed in this family. In addition to Cases 1, 2 and 3, the CDH1 c.1679C>G variant was detected in II-4 and III-15 by further genetic analysis. GC: Gastric cancer; BC: Breast cancer; HCC: Hepatocellular carcinoma.
Figure 2
Figure 2
Representative images obtained from esophagogastroduodenoscopy and computed tomography in Case 1. A and B: Advanced gastric cancer was observed at the posterior wall of the lower gastric body (A) and at the lesser curvature of the middle body (B) in esophagogastroduodenoscopy; C: Metastatic lymph nodes were detected at the lesser curvature of the proximal stomach by abdominal computed tomography (CT) (orange arrows); D: Abdominal CT showed ovarian metastasis during adjuvant chemotherapy (orange arrow).
Figure 3
Figure 3
Representative images obtained from esophagogastroduodenoscopy, colonoscopy and computed tomography in Case 2. A: Advanced gastric cancer was observed at the fundus in esophagogastroduodenoscopy; B: Colonoscopy showed advanced colon cancer at the ascending colon; C: Metastatic lymph nodes at the lesser curvature of the proximal stomach without distant metastasis were identified by abdominal computed tomography (CT) (orange arrow); D: Peritoneal dissemination were observed by abdominal CT during the adjuvant chemotherapy (orange arrow).
Figure 4
Figure 4
Representative images obtained from esophagogastroduodenoscopy and pathological findings in Case 3. A: Multiple small pale lesions were observed mainly at the greater curvature of the gastric body in esophagogastroduodenoscopy (white and black arrows); B: Clearly isolated whitish areas were detected by non-magnifying narrow band imaging (NBI). The image is the lesion indicated by the black arrow in (A); C: Magnifying NBI detected wavy microvessels inside the lesions; D: A gastrectomy mapping study revealed 36 signet ring cell carcinoma (SRCC) foci in the entire gastric mucosa. Red lines indicate SRCC foci; E: Hematoxylin and eosin staining (upper panel) and immunohistochemistry for E-cadherin (lower panel) of the lesion. Loss of immunoreactivity at SRCC foci was confirmed.
See this image and copyright information in PMC

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