Histopathological study using computer database of 10 000 consecutive gastric specimens: (1) benign conditions

Using a computer database, the author investigated the histopathology of 10 000 consecutive gastric specimens, taken in the last 12 years (2002–2013) at the pathology laboratory of a Japanese hospital. Re-observation of the already examined histological sections was done when the histological diagnosis and findings on the computer data base were not very obvious. The gastric specimens were identified as 8579 benign conditions and 1421 malignant lesions. The 8579 benign conditions were comprised almost normal stomach in 74 cases (0.9%), chronic gastritis in 4374 (51.0%), benign gastric peptic ulcer in 2195 (25.6%), foveolar hyperplastic polyp in 1004 (11.7%), fundic gland polyp in 421 (4.9%), adenoma in 487 (5.6%), heterotopic pancreas in 9 (0.1%), pancreatic acinar metaplasia (PAM) in 8 (0.1%), and amyloidosis in 7 (0.1%). Chronic gastritis showed lymphocytic infiltration and frequently showed erosions and intestinal metaplasia. Gastric peptic ulcer showed exudate, necrosis, active inflammation, and regenerative atypia of the epithelium. Foveolar hyperplastic polyp revealed 23 malignant changes and frequently showed dysplastic glands and intestinal metaplasia. Fundic gland polyp demonstrated cystic dilations of fundic gland ducts. Gastric adenoma showed adenomatous proliferation in the superficial mucosa and cystic dilation of the epithelium under the adenoma. Heterotopic pancreas was located in the submucosa and consisted of acinar cells, ducts, and occasionally islets. PAM was a tiny lesion in the mucosa and consisted of only pancreatic acinar cells. Amyloidosis was primary amyloidosis with positive reaction with Congo-red stain.


Materials and methods
The author reviewed his computer database recording 10 000 consecutive gastric specimens, accumulated in the last 12 years at the pathology laboratory of a relatively large hospital in Japan. Histological sections were examined, when appropriate. Clinical records were also reviewed in the computer system. In appropriate cases, an immunohistochemical analysis-for p53 protein (DO-7, Dako Corp, Glostrup, Denmark), cytokeratins (AE1/AE3, Dako), Ki-67 antigens (MIB1, Dako), pancreatic digestive enzymes (polyclonal, Chemicon Corp, Tomecula, USA)was performed with the use of the Dako Envision method (Dako), as previously described [2][3][4].
Gastric adenoma (n ¼ 487) showed adenomatous proliferation in the superficial mucosa and cystic dilation of the   epithelium under the adenoma ( Figure 5). No carcinomatous foci were seen, and sequential biopsies did not show malignant transformation. Twenty-nine patients underwent endoscopic mucosal resection at the patient's request. Heterotopic pancreas (n ¼ 9) was located in the submucosa. Two showed cystic degeneration. Three consisted of acinar cells, ducts, and Langerhans islets (Heinrich type I) ( Figure 6A), and the remaining six were composed of acinar cells and ductal elements (Heinrich type II) ( Figure 6B). The pancreatic acinar cells were positive for pancreatic amylase, lipase and trypsin. Two patients underwent gastrectomy under the clinical diagnosis of gastric carcinoma.
PAM (n ¼ 8) was a tiny lesion in the mucosa ( Figure 7A) and consisted of only pancreatic acinar cells ( Figure 7B). The pancreatic acinar cells were positive for pancreatic amylase, lipase and trypsin.
Amyloidosis (n ¼ 7) was primary amyloidosis ( Figure 8A) with positive reaction to Congo-red stain ( Figure 8B). Six cases were associated with multiple myeloma, and the remaining one was idiopathic.

Discussion
The most common benign gastric condition was chronic gastritis. In the author's experience as a diagnostic pathologist, most person's in Japan show lymphocytic infiltrates or chronic inflammation in the stomach. Erosions and intestinal metaplasia were frequently seen in chronic gastritis. Some patients had clinically acute gastric mucosal lesions presenting as acute gastric pain. It was interesting that two patients showed pyloric stenosis, and the clinical diagnosis of these cases was linitis plastica gastric carcinoma. H. pylori was recognized in 64% in the present series.
Gastric peptic ulcer was the second common benign condition. Pathologically, it frequently showed regenerative atypia of the epithelium. This atypia is occasionally difficult to distinguish from well-differentiated adenocarcinoma. In such cases,   immunohistochemical stainings for p53 protein and Ki-67 antigen are helpful. H. pylori was recognized in 91% in this study.
Fundic gland polyps were small lesions, characterized by cystic dilations of fundic gland ducts. This has no clinical relevance; no malignant transformation was recognized. The gastric fundic gland polyp should be differentiated endoscopically and pathologically from other gastric polypoid lesions including hyperplastic polyp, adenoma, and polypoid carcinoma.
In the present series, no malignant transformation was recognized in gastric adenoma. However, the author thinks that periodical endoscopic follow-up of patients with gastric adenoma is recommended. The most important point about adenoma is its differential diagnosis from extremely well-differentiated adenocarcinoma. This is very difficult in certain cases for pathologists.
Heterotopic pancreas is a congenital malformation [11,12]. However, it can be misdiagnosed as gastric carcinoma and, in the present series, two patients underwent gastrectomy following clinical diagnosis of this condition. Repeated deep biopsies   are necessary to obtain a correct diagnosis. Heterotopic pancreas can show cystic changes and acute hemorrhage [13][14][15]. Such cases shows acute abdominal pain syndrome.
PAM is a microscopic lesion in the mucosa. Unlike heterotopic pancreas, it is composed of only pancreatic acinar cells [16][17][18][19]. It has no clinical relevance, but pathologically may be misdiagnosed as adenocarcinoma. Immunohistochemical demonstration of pancreatic digestive enzymes is of great value.
Gastric amyloidosis is a gastric manifestation of systemic amyloidosis. To demonstrate the amyloid protein, Congo-red stain and immunohistochemical stainings for amyloid-related proteins are of value in the pathological diagnosis. It is necessary to detect the underlining diseases, such as multiple myeloma and chronic inflammation.
In the present study, no cases of gastric familial adenomatosis coli (FAC), gastric Crohn's disease, or non-steroidal antiinflammatory drugs (NSAIDs) were seen, reflecting that gastric lesions of FAC and Crohn's disease are rare in Japan. The absence of NSAIDs may indicate that clinical information on NSAIDs was not provided to the author.
In summary, the present study reported the histopathology of various benign conditions of the stomach.