Helicobacter suis infection is associated with nodular gastritis-like appearance of gastric mucosa-associated lymphoid tissue lymphoma

Abstract

Most patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma are infected with Helicobacter pylori, and eradication therapy is the first-line treatment for localized disease with H pylori infection. However, there were several reports showing effectiveness of eradication therapy in even H pylori negative cases. Gastric MALT lymphomas are endoscopically classified into three common types: superficial, ulcerative, and elevated types. For the past 20 years, we have encountered 200 cases of localized gastric MALT lymphoma. Among them, only 4 cases (2%) showed similar macroscopic findings to those of nodular gastritis (gastric MALT lymphoma with nodular gastritis-like appearance; M-NGA). Here, we compared clinicopathological characteristics and prevalence of non-H pylori Helicobacter (NHPH) infection between M-NGA and other common types of gastric MALT lymphoma. To examine the prevalence of NHPH infection, DNA was extracted from formalin-fixed paraffin-embedded biopsy tissues from four cases of M-NGA, 20 cases of common endoscopic types of gastric MALT lymphoma, and 10 cases of nodular gastritis. We used a highly sensitive polymerase chain reaction assay to detect the presence of five species of NHPH (Helicobacter suis, H felis, H bizzozeronii, H salomonis, and H heilmannii). H suis infection was detected in 4, 2, and 0 of the 4, 20, and 10 cases of M-NGA, other types of gastric MALT lymphoma, and nodular gastritis, respectively. Other NHPH species were not detected in any cases. Complete response rate by eradication therapy was 4/4 in M-NGA cases. Therefore, nodular gastritis-like MALT lymphoma, which shows a very rare phenotype, is closely associated with NHPH infection, and eradication therapy may be the first-choice treatment.

Keywords: Helicobacter suis; eradication therapy; mucosa-associated lymphoid tissue; nodular gastritis; non-H pylori Helicobacter (NHPH).

Figure 1

Characterization of case A1. Endoscopic examination (before eradication): Multiple heterogeneous nodules similar to nodular gastritis in antrum (A) and anglus (B). Indigo carmine dye makes the nodules more obvious in the antrum (C) and anglus (D). Endoscopic examination (after eradication): no nodules in the antrum (E) or anglus (F), even with indigo carmine dye in the antrum (G) and anglus (H). Pathological examination (before eradication): Lymphoma cells proliferate diffusely and form heterogeneous nodules with lymphoid hyperplasia. HE, ×100 (I). Atypical lymphoid cells invading the epithelium, resulting in the destruction of mucosal glands and formation of lymphoepithelial lesions. HE, ×400 (J). Immunohistochemistry (before eradication): Neoplastic cells are positive for CD20 (K), negative for CD3 (L), and positive for CD79a (M). PCR assay (before eradication): Positive for Helicobacter suis (253 bp); negative for other non‐H pylori Helicobacter (N). Biopsies taken from areas indicated with yellow arrows showed pathological findings compatible with mucosa‐associated lymphoid tissue lymphoma. Abbreviation: HE, hematoxylin and eosin

Figure 2

Characterization of case A2. Endoscopic examination (before eradication): Multiple heterogeneous nodules similar to nodular gastritis in antrum (A) and anglus (B). Indigo carmine dye makes the nodules more obvious in the antrum (C) and anglus (D). Endoscopic examination (after eradication): no nodules in the antrum (E) or anglus (F), even with indigo carmine dye in the antrum (G) and anglus (H). Pathological examination (before eradication): lymphoma cells proliferate diffusely and form heterogeneous nodules with lymphoid hyperplasia. HE, ×100 (I). Atypical lymphoid cells invading the epithelium, resulting in the destruction of mucosal glands and formation of lymphoepithelial lesions. HE, ×400 (J). Immunohistochemistry (before eradication): Neoplastic cells are positive for CD20 (K), negative for CD3 (L), and positive for CD79a (M). PCR assay (before eradication): Positive for Helicobacter suis (253 bp); negative for other non‐H pylori Helicobacter (N). Biopsies taken from areas indicated with yellow arrows showed pathological findings compatible with mucosa‐associated lymphoid tissue lymphoma. Abbreviation: HE, hematoxylin and eosin

Figure 3

Characterization of case A3. Endoscopic examination (before eradication): Multiple heterogeneous nodules similar to nodular gastritis in antrum (A) and anglus (B). Indigo carmine dye makes the nodules more obvious in the antrum (C) and anglus (D). Endoscopic examination (after eradication): no nodules in the antrum (E) or anglus (F), even with indigo carmine dye in the antrum (G) and anglus (H). Pathological examination (before eradication): lymphoma cells proliferate diffusely and form heterogeneous nodules with lymphoid hyperplasia. HE, ×100 (I). Atypical lymphoid cells invading the epithelium, resulting in the destruction of mucosal glands and formation of lymphoepithelial lesions. HE, ×400 (J). Immunohistochemistry (before eradication): Neoplastic cells are positive for CD20 (K), negative for CD3 (L), and positive for CD79a (M). PCR assay (before eradication): Positive for Helicobacter suis (253 bp); negative for other non‐H pylori Helicobacter (N). Biopsies taken from areas indicated with yellow arrows showed pathological findings compatible with mucosa‐associated lymphoid tissue lymphoma. Abbreviation: HE, hematoxylin and eosin

Figure 4

Characterization of case A4. Endoscopic examination (before eradication): Multiple heterogeneous nodules similar to nodular gastritis in antrum (A) and anglus (B). Indigo carmine dye makes the nodules more obvious in the antrum (C) and anglus (D). Endoscopic examination (after eradication): No nodules in the antrum (E) or anglus (F). Status of monoclonal IgH rearrangement (G). Pathological examination (before eradication): Lymphoma cells proliferate diffusely and form heterogeneous nodules with lymphoid hyperplasia. HE, ×100 (H). Atypical lymphoid cells invading the epithelium, resulting in the destruction of mucosal glands and formation of lymphoepithelial lesions. HE, ×400 (I). Immunohistochemistry (before eradication): Neoplastic cells are positive for CD20 (J), negative for CD3 (K), and positive for CD79a (L). PCR assay (before eradication): Positive for Helicobacter suis (253 bp); negative for other non‐H pylori Helicobacter (M). Biopsies taken from areas indicated with yellow arrows showed pathological findings compatible with mucosa‐associated lymphoid tissue lymphoma. Abbreviation: HE, hematoxylin and eosin

Figure 5

Characterization of cases A5, A6, and A7. Cases A5 and A6: Endoscopic pictures of common type MALT lymphoma with Helicobacter suis infection. In case A5, the superficial phenotype of gastric MALT lymphoma was observed in the gastric body under white light (A) and chromoendoscopy (B). In case A6, the superficial phenotype was observed in the gastric body under white light (C) and chromoendoscopy (D). Mild nodular gastritis without MALT lymphoma was observed in the gastric antrum under white light (E) and chromoendoscopy (F). Case A7: Representative endoscopic pictures of nodular gastritis. Endoscopic examination (before eradication): Multiple homogeneous nodules are seen in the antrum. Whitish spots exist on the top of each nodule (G). No nodule is observed in the gastric anglus (H). Mild atrophy is observed in the gastric body (I). Indigo carmine dye makes the nodules more obvious in the antrum (J). Abbreviation: MALT, mucosa‐associated lymphoid tissue