Helicobacter pylori-negative Gastric Cancer

ABSTRACT

Helicobacter pylori (H. pylori)-negative gastric cancer is diagnosed when gastric malignancies are found in patients in H. pylori-naïve stomachs. There are four types of noncardiac H. pylori-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 H. pylori infection, strict criteria are required for diagnosing an H. pylori-naïve stomach. Both invasive and noninvasive H. pylori tests should show negative results in a subject without a history of H. pylori 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 H. pylori. 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 H. pylori infiltration, and only a mild degree of mononuclear cell infiltration is permitted. The types and characteristics of noncardiac H. pylori-negative gastric cancers are summarized in this review, along with current diagnostic challenges found in Korea.