Helicobacter pylori-negative Gastric Cancer

Abstract

<i>Helicobacter pylori (H. pylori)</i>-negative gastric cancer is diagnosed when gastric malignancies are found in patients in <i>H. pylori</i>-naïve stomachs. There are four types of noncardiac <i>H. pylori</i>-negative gastric cancers. The signet ring cell-type poorly cohesive carcinoma is most common, followed by the chief cell-predominant type gastric adenocarcinoma of the fundic gland. Extremely well-differentiated adenocarcinoma of the corpus and well-differentiated pyloric gland cancers are rare outside Japan because of country-specific differences in diagnostic criteria. In endemic areas of <i>H. pylori</i> infection, strict criteria are required for diagnosing an <i>H. pylori</i>-naïve stomach. Both invasive and noninvasive <i>H. pylori</i> tests should show negative results in a subject without a history of <i>H. pylori</i> infection. Furthermore, the serum pepsinogen (PG) assay and endoscopic findings of the background gastric mucosa are required to discriminate subjects with past infections owing to spontaneous regression or unintended eradication of <i>H. pylori</i>. There should be no gastric corpus atrophy (PG I ≤70 ng/mL and PG I/II ≤3.0). Gastroscopy should reveal a regular arrangement of collecting venules without gastric xanthoma, metaplastic gastritis, or advanced atrophy over the angle. On biopsy, there should be no gastric atrophy, intestinal metaplasia, neutrophils, or <i>H. pylori</i> infiltration, and only a mild degree of mononuclear cell infiltration is permitted. The types and characteristics of noncardiac <i>H. pylori</i>-negative gastric cancers are summarized in this review, along with current diagnostic challenges found in Korea.