Characterization of Chronic Gastritis in Lynch Syndrome Patients With Gastric Adenocarcinoma

Abstract

Background: Gastric cancer is one of the Lynch syndrome (LS)-associated malignancies. Previous studies have suggested that LS patients with gastric cancer also had chronic atrophic gastritis in the background mucosa, but further histologic characterization was not attempted. This study aims to understand the histologic features of background chronic gastritis in LS patients with gastric adenocarcinoma.

Methods: Eleven LS-associated gastric cancer cases were collected from five institutions. Demographics and clinical features were retrieved by review of medical charts. Pathological material was reviewed for tumor location and histologic type. In addition, non-neoplastic gastric mucosa was assessed for inflammation (chronic and active), atrophy, intestinal metaplasia (IM) in the antrum and body, as well as pyloric gland metaplasia and enterochromaffin-like (ECL) cell hyperplasia in the body.

Results: Eleven LS patients with gastric cancer (four male and seven female) with a mean age of 63 years (range: 23 - 83) were included. Ten (90.9%) had personal cancer histories; however none of the patients had family history of gastric cancer. Eight (72.7%) patients underwent gastrectomy and three had endoscopic resection. Nine (81.8%) patients had tumor in the fundus and/or body and two had tumor present in the antrum. Seven (63.6%) cases were intestinal type or mixed type carcinoma, and the remaining four were signet ring cell carcinoma. Eight (of 11, 72.7%) patients had chronic gastritis, five (45.4%) had atrophy, and four (36.3%) had intestinal metaplasia. Four of five patients with both antrum and body mucosa available for evaluation (80%), demonstrated body-predominant chronic gastritis. Four patients had germline MLH1 alterations and all of these patients had chronic gastritis, including one Helicobacter pylori (H. pylori) gastritis and three H. pylori-negative gastritis.

Conclusions: None of LS patients with gastric cancer in our cohort had a family history of gastric cancer. Gastric adenocarcinomas in LS patients were primarily located in the fundus and/or body. Two-thirds of these tumors were of intestinal type and had a background chronic, H. pylori-negative gastritis. These results support a chronic atrophic gastritis with intestinal metaplasia-dysplasia-carcinoma sequence in LS-related gastric tumorigenesis, particularly in MLH1-mutated LS patients.