Current Status of the Spectrum and Therapeutics of Helicobacter pylori-Negative Mucosa-Associated Lymphoid Tissue Lymphoma

Abstract

Helicobacter pylori (HP)-unrelated mucosa-associated lymphoid tissue (MALT) lymphoma includes the majority of extragastric MALT lymphomas and a small proportion of gastric MALT lymphomas. Although the role of first-line antibiotics in treating HP-negative gastric MALT lymphomas remains controversial, HP eradication therapy (HPE)-like regimens may result in approximately 20–30% complete remission (CR) for patients with localized HP-negative gastric MALT lymphoma. In these patients, H. heilmannii, H. bizzozeronii, and H. suis were detected in sporadic gastric biopsy specimens. Extragastric MALT lymphoma is conventionally treated with radiotherapy for localized disease and systemic chemotherapy for advanced and metastatic diseases. However, a proportion of extragastric MALT lymphomas, such as ocular adnexal lesions and small intestinal lesions, were reported to be controlled by antibiotics for Chlamydophila psittaci and Campylobacter jejuni, respectively. Some extragastric MALT lymphomas may even respond to first-line HPE. These findings suggest that some antibiotic-responsive tumors may exist in the family of HP-negative MALT lymphomas. Two mechanisms underlying the antibiotic responsiveness of HP-negative MALT lymphoma have been proposed. First, an HPE-like regimen may eradicate the antigens of unknown bacteria. Second, clarithromycin (the main component of HPE) may have direct or indirect antineoplastic effects, thus contributing to the CR of these tumors. For antibiotic-unresponsive HP-negative MALT lymphoma, high-dose macrolides and immunomodulatory drugs, such as thalidomide and lenalidomide, have reported sporadic success. Further investigation of new treatment regimens is warranted.

Synchronous early gastric and intestinal mucosa-associated lymphoid tissue lymphoma in a Helicobacter pylori-negative patient: A case report

“…Autoimmune diseases such as Sjogren’s syndrome, IgG4-related diseases, and obesity also increase the risk of primary MALT lymphoma[ 5 ]. Another possibility is infection with bacteria other than H. pylori , which could explain why the eradication of H. pylori can treat some H. pylori -negative MALT lymphomas[ 6 ].…”

Development of serological assays to identifyHelicobacter suisandHelicobacter pyloriinfections

“…H. pylori eradication therapy is the first choice for treating gastric MALT lymphoma in H. pylori -infected patients, and even in H. pylori -negative patients, since H. pylori -negative patients have also been shown to respond to eradication therapy. 37 Yasuda et al . recently reported finding H. suis infection even in their patients with gastric cancer.…”

“…They concluded that H. suis was the most common NHPH that infected human stomachs 13 . The H. suis infection leads to diseases such as gastric mucosa-associated lymphoid tissue (MALT) lymphoma, nodular gastritis, chronic gastritis, and peptic ulcer [14][15][16][17][18][19][20] . However, the above reports did not provide proof of H. suis or other NHPH infection because they only used PCR assay and did not isolate the bacteria or analyze the isolated bacteria's genome to identify the infecting bacteria.…”

Bacterial infection-driven lymphomagenesis

“…Although a false-negative test cannot be completely ruled out, these results seem to indicate that other bacteria may be associated with the lymphoma development. Gastric MZL, for example, may occur in patients with infection from H. heilmannii or other helicobacter species, the eradication of which may lead to lymphoma regression [47]. Gut microbiota might also be implicated in some antibiotic-responsive H. pylori -negative gastric MALT lymphoma [47].…”