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Intestinal-type gastric dysplasia in Helicobacter pylori-naïve patients

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Abstract

Gastric dysplasia and gastric cancer in Helicobacter pylori (Hp)-naïve patients usually exhibit a gastric phenotype, reflecting gastric mucosa without intestinal metaplasia (IM). We showed that intestinal-type gastric dysplasia (IGD) rarely occurs in the Hp-naïve stomach. In the last 10 years, we treated 1760 gastric dysplasia and gastric cancer patients, with 3.6% (63/1760) being Hp-naïve. Among these, ten were diagnosed with 14 IGDs and enrolled in this retrospective analysis. All lesions were observed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). We analyzed their endoscopic and microscopic features and patient demographics. Five men and five women aged 64 ± 21 years were included. WLE showed the depressed lesions mimicking a benign raised erosion in the prepyloric compartment. Multiple growths were confirmed in 30% (3/10) of patients. NBIME showed a near-regular microstructure and capillaries in 50% (7/14) of lesions with a gastritis-like appearance. Histologically, background mucosa was non-atrophic pyloric gland tissue, but 40.0% of samples (4/10) contained sporadic IM. Most of the lesions (8/14) were low-grade dysplasia, and others had a high-grade component, with one progressing to intramucosal carcinoma. The neoplastic surface was widely covered with foveolar epithelium in 57.1% (8/14). Immunohistochemically, neoplastic cells expressed CDX2 in all patients (14/14), MUC2 and CD10 in 92.9% (13/14), MUC5AC in 14% (2/14), and no expression of MUC6, showing an intestinal phenotype. Ki-67 was overexpressed with a mean labeling index of 58.3 ± 38.5%, and p-53 was overexpressed in 92.9% (13/14), regardless of the dysplastic grade. The IGD rarely occurs in Hp-naïve patients with distinctive clinicopathologic characteristics.

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Authors and Affiliations

  1. Department of Endoscopy, Shimane University Hospital, Zip code 693-8501, 89-1 Enya, Izumo, Japan

    Kotaro Shibagaki

  2. Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan

    Ayako Itawaki, Kenichi Kishimoto, Yusuke Takahashi, Satoshi Kotani, Tsuyoshi Mishiro, Naoki Oshima, Kousaku Kawashima, Norihisa Ishimura & Shunji Ishihara

  3. Department of Gastroenterology, Shimane Prefectural Central Hospital, Izumo, Japan

    Yoichi Miyaoka

  4. Department of Pathology, Shimane Prefectural Central Hospital, Izumo, Japan

    Hideyuki Onuma

  5. Department of Pathology, National Hospital Organization Hamada Medical Center, Hamada, Japan

    Makoto Nagasaki

  6. Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan

    Mamiko Nagase, Asuka Araki & Kyuichi Kadota

  7. Department of Pathology, Shiga University of Medical Science, Otsu, Japan

    Ryoji Kushima

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Contributions

Conception and design: Kotaro Shibagaki.

Analysis and interpretation of the data: Kotaro Shibagaki, Ayako Itawaki, Yoichi Miyaoka, Kenichi Kishimoto, Hideyuki Onuma, Makoto Nagasaki, Mamiko Nagase, Asuka Araki, Kuichi Kadota, and Ryoji Kushima.

Enrollment of patients: Yusuke Takahashi, Ayako Itawaki, Satoshi Kotani, Kenichi Kishimoto, Naoki Oshima, and Kousaku Kawashima.

Critical revision of the article for important intellectual content: Tsuyoshi Mishiro, Norihisa Ishimura, Kuichi Kadota, Ryoji Kushima, and Shunji Ishihara.

Final approval of the article: Shunji Ishihara.

Corresponding author

Correspondence to Kotaro Shibagaki.

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Ethics approval

The study protocol was approved by the medical ethics committee of Shimane University Hospital (study number: 4905, Date: September 18, 2020). Informed consent was obtained in the form of opt-out on the website from all participants.

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Fig. S1

Typical gastritis-like appearance. Case 4: The depressed lesion with raised surrounding mucosa is seen in non-atrophic antral area (indicated with yellow arrow), which resembles a benign raised erosion (A). However, NBIME shows irregular microstructure and capillaries, suggesting neoplastic characteristics (B). Histologic examination shows the high-grade dysplasia with irregular architecture (C) and polygonal nuclei with loss of polarity (D). Case 6: Similar depressed lesion is seen in non-atrophic antral compartment (indicated with blue arrow) (E). NBIME shows almost regular microstructure, suggesting non-neoplastic characteristics (F). Histologic examination reveals a low-grade dysplasia (G) superficially covered with foveolar epithelium (H). (PNG 37827 kb)

High Resolution (TIF 8630 kb)

Fig. S2

Multiple IGD case (Case 10); modified from reference [14]. Three depressed lesions are seen in the non-atrophic prepyloric area (indicated with colored arrows) (A). Two lesions show an irregular microstructure that is partially regular at the center part of the lesions (indicated with black arrow) (B and C). The other one shows an irregular papillary microstructure (D). Neoplastic mapping on the resected specimen (E). The yellow-arrowed lesion is histologically low-grade dysplasia that is superficially covered with foveolar epithelium (F). Solitary erosion is seen at another prepyloric site (G). Histologic examination by biopsy shows intestinal metaplasia (H). (PNG 40602 kb)

High Resolution (TIF 9141 kb)

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Shibagaki, K., Itawaki, A., Miyaoka, Y. et al. Intestinal-type gastric dysplasia in Helicobacter pylori-naïve patients. Virchows Arch 480, 783–792 (2022). https://doi.org/10.1007/s00428-021-03237-9

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