Cold snaring biopsies to increase screening efficacy during endoscopic surveillance of patients at high risk of diffuse gastric cancer

Diffuse gastric cancer (DGC) is a poorly differentiated adenocarcinoma of the stomach characterized by independent “signet-ring” cells that invade the gastric wall with mainly submucosal infiltration resulting in delayed diagnosis [1]. Mutations in the CDH1 gene, encoding E-cadherin, have been identified in families with multiple cases of gastric cancer, with a 50%–80% increased risk of DGC in carriers [2]. In cases with a proven constitutional CDH1 mutation, guidelines recommend prophylactic total gastrectomy between the ages of 20 and 30 years, or endoscopic surveillance if surgery is refused or postponed [3].

Given the multiple possible localizations and frequency of small carcinomatous foci, a minimum of 30 biopsies divided into six zones using standard forceps is recommended [3] [4]. However, multiple sampling of the gastric mucosa using conventional biopsy forceps still represents a limited surface area that can be analyzed. Increasing the size of the biopsy sample using cold snaring may increase diagnostic sensitivity.

We report here the case of a 33-year-old patient with regular endoscopic surveillance after identification of a CDH1 mutation in a familial context.

Gastroscopy and endoscopic ultrasound were performed, with no findings of macroscopic abnormalities, parietal thickening, or suspicious adenopathy ([Video 1]). To increase the size of the tissue sampled for histological analysis, 24 cold snaring biopsies (6 upper fundus, 6 body, 6 lower body, and 6 antrum) were performed. Pathological analysis revealed a single focal area of independent cell adenocarcinoma in the chorion (pTis) seen only in one sample. A gastrectomy was then performed, with a millimetric focal adenocarcinoma with signet-ring cells on the surgical specimens.

Gastric sampling using random cold snaring of the whole stomach with visualization of the corresponding resected area.Video 1

Histopathological analysis was improved, with the average size of biopsy fragments being significantly larger with cold snaring than with standard forceps, and with a reduction in crush artifacts ([Fig. 1]).

Fig. 1 Histopathological characterization (hematoxylin and eosin) of specimens from patients followed endoscopically due to familial predisposition for CDH1 mutation-related gastric adenocarcinoma. a Cold snaring biopsy. b Standard forceps biopsy. c The mean size of biopsy fragment was significantly increased with cold snaring (patient A) compared with standard forceps (patients B and C), based on the examination of three patients with 18, 30, and 28 fragments biopsied, respectively (one-way analysis of variance with Dunnett’s multiple comparisons, ****P < 0.0001; GraphPad Prism v10.0.0). d Cold snaring sample: the crushing artifacts often observed with standard forceps were not seen in the cold snaring biopsies (×20 magnification; e ×40 magnification).

In conclusion, this case suggests that large samples obtained with cold snaring could potentially decrease the focal adenocarcinoma miss rate in CDH1 mutation carriers.

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Conflict of Interest

The authors declare that they have no conflict of interest.

• References

• 1 Ikoma N, Agnes A, Chen H-C. et al. Linitis plastica: a distinct type of gastric cancer. J Gastrointest Surg 2020; 24: 1018-1025
• 2 Hansford S, Kaurah P, Li-Chang H. et al. Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol 2015; 1: 23-32
• 3 Fitzgerald RC, Hardwick R, Huntsman D. et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 2010; 47: 436-444
• 4 van der Post RS, Vogelaar IP, Carneiro F. et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet 2015; 52: 361-374

Publication History

Article published online:
01 March 2024