Clin Endosc.  2024 Jul;57(4):486-494. 10.5946/ce.2023.258.

Clinicopathological and endoscopic features of Helicobacter pylori infection-negative gastric cancer in Japan: a retrospective study

• Imamura K
• Yao K
• Nimura S
• Kanemitsu T
• Miyaoka M
• Ono Y
• Ueki T
• Tanabe H

• KMID: 2558105
• DOI: http://doi.org/10.5946/ce.2023.258

Abstract

Background/Aims
Helicobacter pylori infection-negative gastric cancer (HPNGC) has not been systematically investigated in consecutive patients. Hence, this study aimed to investigate the clinicopathological and endoscopic features of HPNGC.
Methods
This single-center retrospective study selected participants from patients with gastric cancer who were treated at the Fukuoka University Chikushi Hospital between January 2013 and December 2021. Only patients diagnosed with HPNGC were enrolled, and their clinicopathological and endoscopic features were analyzed in detail.
Results
The prevalence of HPNGC in the present study was 2.6% (54/2112). The types of HPNGC observed in each gastric region were as follows: advanced gastric cancer was observed in the cardia; gastric adenocarcinoma of fundic-gland differentiation, gastric adenocarcinoma of foveolar-type presenting with whitish elevation and raspberry-like foveolar-type gastric adenocarcinoma, gastric adenocarcinoma arising in polyposis, and gastric adenocarcinoma with autoimmune gastritis were observed in the fundic gland region ranging from the gastric fornix to the gastric body; signet-ring cell carcinoma was observed in the gastric-pyloric transition region ranging from the lower gastric body to the gastric angle; and well-differentiated tubular adenocarcinoma with low-grade atypia was observed in the antrum.
Conclusions
This study revealed that tumors from each gastric region exhibited distinct macroscopic and histological types in HPNGC.

Keyword

Gastric cancer; infections; Magnifying endoscopy; Narrow-band imaging

Figure

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  Fig. 1. Endoscopic findings of gastric adenocarcinoma of fundic-gland type. (A) Conventional endoscopic image: a pale subepithelial tumor-like elevated lesion is observed in the fundus. Dilated vessels can be seen in the elevated region. (B) Image of the lesion obtained using magnifying endoscopy with narrow-band imaging. Upon observing the surrounding area, the lesion shows no marked changes in the microvascular (MV) or microsurface (MS) pattern, and there is no clear demarcation line (DL). The microvessel has a polygonal closed-loop morphology, and the vessels are uniform in shape, arranged regularly, and symmetrically distributed. The marginal crypt epithelium has an oval or arc-shaped morphology, is uniform in shape, arranged regularly, and distributed symmetrically. According to the vessel plus surface classification system, the lesion is classified as having a regular MV pattern plus a regular MS pattern without DL. In other words, the magnifying endoscopic findings of the lesion does not fulfill the diagnostic criteria for cancer.

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  Fig. 2. Endoscopic findings of gastric adenocarcinoma of fundic-gland mucosa type. (A) Conventional endoscopic image. The lesion has a slightly red mucosa in the posterior wall of the lower gastric body. (B) Image of the lesion obtained using magnifying endoscopy with narrow-band imaging. Upon observing the background mucosa, the elevated lesion shows marked changes in both the microvascular (MV) and microsurface (MS) patterns, and there is a clear demarcation line (DL) (yellow arrows). Regarding the MV pattern, the lesion consists of microvessels with open- and closed-loop formation, and the vessels are not uniform in shape, distributed asymmetrically, and arranged irregularly. Regarding the MS pattern, the marginal crypt epithelium (MCE) has a curved or oval morphology. The MCE is nonuniform in shape, distributed asymmetrically, and arranged irregularly. According to the vessel plus surface classification system, the lesion was classified as having an irregular MV pattern plus an irregular MS pattern with a DL, and was diagnosed as cancer.

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  Fig. 3. Endoscopic and histopathological findings of gastric adenocarcinoma of foveolar-type presenting with whitish elevation. (A) Conventional endoscopic findings. A markedly whitish elevated lesion is observed in the greater curvature of the upper gastric body. (B) Image of the lesion obtained using magnifying endoscopy with narrow-band imaging. Upon observation of the background mucosa, the lesion shows marked changes both in microvascular (MV) and microsurface (MS) patterns, and there is a clear demarcation line (DL) (yellow arrows). With respect to the MV pattern, the lesion consists of microvessels with open- and closed-loop formation, and the vessels are not uniform in shape, distributed asymmetrically, and arranged irregularly. With respect to the MS pattern, the marginal crypt epithelium (MCE) has a curved or oval morphology. The MCE is nonuniform in shape, distributed asymmetrically, and arranged irregularly. According to the vessel plus surface classification system, the lesion was classified as having an irregular MV pattern plus an irregular MS pattern with a DL, and was diagnosed as cancer. (C) Histopathological image of gastric adenocarcinoma of foveolar-type presenting with whitish elevation (hematoxylin and eosin stain, ×100). Tall cells with clear cytoplasm are proliferating in a papillary pattern. They exhibit histopathological features of foveolar-type gastric adenocarcinoma.

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  Fig. 4. Endoscopic and histopathological findings of adenocarcinoma in familial adenomatous polyposis. (A) Conventional endoscopic image． Multiple fundic gland polyps can be seen developing in a region ranging from the gastric fornix to the gastric body. A whitish area is observed in the greater curvature of the upper gastric body. (B) Imaging result of indigocarmine staining. The whitish area appears to have a smaller granular elevation than the surrounding area. (C) Image of the lesion obtained using magnifying endoscopy with narrow-band imaging. Upon observation of the background mucosa, the lesion shows marked changes both in the microvascular (MV) and microsurface (MS) patterns, and there is a clear demarcation line (DL) (yellow arrows). With respect to the MV pattern, the lesion consists of microvessels with open- and closed- loop formation, and the vessels are not uniform in shape, distributed asymmetrically, and arranged irregularly. With respect to the MS pattern, almost no marginal crypt epithelium can be visualized. According to the vessel pulse surface classification system, the lesion was classified as having an irregular MV pattern plus an absent MS pattern with a DL, and was diagnosed as cancer. (D) Histopathological image of adenocarcinoma in familial adenomatous polyposis (hematoxylin and eosin stain, ×40). The histological findings of well-differentiated tubular adenocarcinoma are observed (red line). The mucosa surrounding the tumor exhibits the findings of fundic gland polyps with fundic gland hyperplasia and cyst formation (blue line).

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  Fig. 5. Endoscopic and histopathological findings of well-differentiated adenocarcinoma with low-grade atypia. (A) Conventional endoscopic image. There are multiple small red depressed lesions in the antrum. The yellow arrow indicates the lesion. (B) Image of the lesion obtained using magnifying endoscopy with narrow-band imaging. The lesion shows marked changes in both microvascular (MV) and microsurface (MS) patterns, with a clear demarcation line (DL) (yellow arrows). With respect to the MV pattern, the lesion mainly consists of microvessels with open-loop formation, and the vessels are not uniform in shape, distributed asymmetrically, and arranged irregularly. With respect to the MS pattern, the marginal crypt epithelium (MCE) has a curved morphology. The MCE is nonuniform in shape, distributed asymmetrically, and arranged irregularly. According to the vessel plus surface classification system, the lesion was classified as having an irregular MV pattern plus an irregular MS pattern with a DL, and was diagnosed as cancer. (C) Histopathological appearance (hematoxylin and eosin stain, ×40). The tumor shows slightly irregular branching ducts with mildly enlarged nuclei and is diagnosed as a well-differentiated adenocarcinoma with low-grade atypia (red arrow). (D) Histopathological findings in the background mucosa of the lesion (hematoxylin and eosin stain, ×40). Gastric intestinal metaplasia is observed.

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  Fig. 6. Characteristics of the preferential development sites of Helicobacter pylori infection-negative gastric cancer. (1) Cardia: advanced gastric cancer. (2) Fundic gland region ranging from the gastric fornix to the gastric body: adenocarcinoma of fundic gland differentiation (adenocarcinoma of fundic-gland type, adenocarcinoma of fundic-gland mucosa type, adenocarcinoma of mixed fundic and pyloric-mucosa types), gastric adenocarcinoma of foveolar-type (gastric adenocarcinoma of foveolar-type presenting with whitish elevation, raspberry-like foveolar-type gastric adenocarcinoma), gastric adenocarcinoma arising in polyposis (adenocarcinoma in Peutz-Jeghers syndrome, adenocarcinoma in familial adenomatous polyposis), and gastric adenocarcinoma with autoimmune gastritis. (3) Gastric-pyloric transition region ranging from the lower gastric body to the gastric angle: signet-ring cell carcinoma. (4) Antrum: well-differentiated adenocarcinoma with low-grade atypia.

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