Gastric Adenocarcinoma in Helicobacter pylori-Negative Autoimmune Gastritis: A Case Report and Literature Review

Abstract

Recent studies have suggested that gastric cancer does not occur in patients with Helicobacter pylori-negative autoimmune gastritis (AIG); however, this notion is controversial. We encountered a case of gastric cancer associated with AIG in which H. pylori infection was excluded. A woman in her 70s was referred to our hospital for endoscopic resection of an antral adenoma. An H. pylori antibodies test, stool antigens test, H. pylori culture, and histological analysis using Giemsa staining yielded negative results. AIG was suspected because the antrum was endoscopically normal but the body was severely atrophic, which are typical findings of AIG. Anti-parietal cell antibodies were 40-fold positive, the gastrin level was 2950 pg/ml, and the pepsinogen I level, pepsinogen II level, and pepsinogen I/II ratio were 6.3 ng/ml, 5.7 ng/ml, and 1.1, respectively. A pathological examination of the gastric body revealed severe oxyntic atrophy with hyperplasia of enterochromaffin-like cells, whereas the antrum showed no pyloric gland atrophy or inflammation. These findings indicated that the patient had H. pylori-negative AIG. Four years later, a depressed lesion in the lower body and a flat lesion at the angle were observed; the former was a poorly cohesive carcinoma, and the latter was a differentiated adenocarcinoma. Surgical resection revealed that the lesion in the lower body was a poorly cohesive carcinoma invading the submucosa with vascular involvement, whereas the lesion in the angle was an intramucosal differentiated adenocarcinoma. A review of previous studies of gastric cancer with H. pylori-negative AIG suggested that patients with histologically and serologically advanced gastritis are at high risk for carcinogenesis. Even in H. pylori-negative cases, severe gastric mucosal atrophy in AIG cases may indicate a carcinogenic risk; therefore, surveillance for gastric cancer is especially recommended for these cases. Large cohort studies on the association between H. pylori-negative AIG and gastric cancer are warranted.

Keywords: autoimmune gastritis; endoscopy; gastric cancer; helicobacter pylori; histology; pepsinogen.

Figure 1. Endoscopic and histologic findings of intestinal-type adenoma in the gastric antrum

A) White light endoscopy reveals an elevated round lesion in the gastric antrum adjacent to the pylorus ring. B) Histological findings of the endoscopically resected specimen. The pyloric mucosa surrounding the intestinal-type adenoma with low-grade dysplasia shows no atrophy or intestinal metaplasia with corkscrew-like foveolar hyperplasia, suggesting reactive gastropathy (hematoxylin and eosin staining; magnification, ×40).

Figure 2. Endoscopic findings of background mucosa suggestive of autoimmune gastritis

A) Conventional white light endoscopic findings of the gastric antrum showing no atrophy. B) Conventional white light endoscopic findings of the gastric body showing severe atrophy with marked vascular visibility on the entire great curvature of the gastric body and scattered hyperplastic polyps. Endoscopy of the gastric antrum and body reveals “corpus-dominant advanced atrophy,” which is a typical feature of autoimmune gastritis (AIG).

Figure 3. Histological findings of background mucosa compatible with autoimmune gastritis (AIG) without current and past H. pylori infection

A) Histological findings of the oxyntic mucosa biopsy reveal a marked reduction in the oxyntic gland, including the absence of parietal cells, intestinal metaplasia, pseudopyloric metaplasia, and thickened muscularis mucosae (hematoxylin and eosin staining; magnification, ×100). B) Immunohistochemical staining with chromogranin A identifies enterochromaffin-like cells that line the long portion of the gastric pit, indicating “linear hyperplasia,” and form small clusters, indicating an endocrine cell micronest (arrowhead) (Chromogranin A staining; magnification, ×100). C) Histological findings of the pyloric mucosa biopsy reveal no pyloric gland atrophy or intestinal metaplasia with foveolar hyperplasia, suggesting reactive gastropathy. Histological findings in the body and antrum are typical of end-stage AIG (hematoxylin and eosin staining; magnification, ×100). D) Complete intestinal metaplasia is recognized in the background mucosa of the corpus (hematoxylin and eosin staining; magnification, ×200).

Figure 4. Endoscopic findings of gastric cancers in the angle and body

A) Conventional white light endoscopy of the gastric angle. A whitish-raised lesion is observed in the angle. The biopsy results indicate differentiated adenocarcinoma. B) Conventional white light endoscopy of the gastric body. An erythematous depressed lesion with a nodule at the margins is observed in the lower corpus of the greater curvature, where a poorly cohesive carcinoma is detected (arrowhead). At this angle, a whitish-raised lesion (A) is observed (arrow).

Figure 5. Histological findings of the resected specimen of gastric cancer in the angle

A)  Microscopic findings of the resected specimen of the lesion in the gastric angle. Differentiated adenocarcinoma localized in the mucosa without invasion into the submucosal layer is observed (hematoxylin and eosin staining; magnification, ×40). B) Highly magnified image. The right side of the specimen shows a well-differentiated adenocarcinoma with minimal glandular alterations, whereas the left side shows severe glandular alterations (hematoxylin and eosin staining; magnification, ×200).

Figure 6. Histological findings of the resected specimen of gastric cancer in the body

A) Microscopic findings of the resected specimen of the lesion in the gastric body. Poorly cohesive carcinoma invading the submucosal layer is observed (hematoxylin and eosin staining; magnification, ×40). B) Highly magnified image. Classic signet ring cell carcinoma is observed in the superficial layer. Poorly cohesive carcinoma is observed in the deep layer (hematoxylin and eosin staining; magnification, ×200). C) Cytokeratin AE1/AE3 staining indicates that the tumor has invaded the deeper submucosal layers just above the muscle layer (arrowhead) (Cytokeratin AE1/AE3 staining; magnification, ×12.5). D) Elastica van Gieson staining of the vein reveals intravascular invasion of tumor cells, suggesting positive lymphovascular invasion (Elastica van Gieson staining; magnification, ×200).