1. Helicobacter pylori and Gastric Lymphoma
Marta Pisarska
DT204/2

2. Overview Gastric Lymphoma
B-cells Extranodal Marginal Zone Lymphoma of Mucosa Associated Tissue
Helicobacter pylori infection and it’s association with this cancer
Diagnosis and confirmation of presence of H.pylori
Treatment of Gastric Lymphoma with focus on H. pylori eradication

3. Gastric Lymphoma
„Tumour of haematological cells, which develops within the lymphatic system of the gastric area”
Can affect lymphatic organs or be extranodal
Divided into Hodgkin's and Non Hodgkins types of lymphomas
Indolent or Aggressive
Affects T and B lymphocytes
Zullo A, Hassan C, Ridola L, Repici A, Manta R, AndianiA. Gastric MALT lymphoma:old and new insights. Annals of Gastroenterology. 2014; 27(1): 27–33.

4. Extranodal Gastric Lymphoma
Extranodal lymphoma occurs most commonly in the gastric area
In 2/3 of cases it affects the stomach
Two main types of primary extranodal gastric lymphoma are identified:
Extranodal Marginal Zone Lymphoma of Mucosa Associated Tissue (MALT)
Diffuse Large B-cell Lymphoma of Stomach (DLBCL)
Other less common types include Follicular and Mantle cell gastric lymphomas.
Witkowska M, Smolewski P. Helicobacter pylori infection, Chrinic Inflammation, and Genomic Transformations in Gastric MALT Lymphoma. Mediators of Inflammation :523170

5. Extranodal Marginal Zone Lymphoma of MALT
„Arises from MALT tissue rich in B-lymphocytes, due to a normal immune response to chronic inflammation or due to an autoimmune disease”
Can occur in any organ
H.pylori infection is considered to be the most important risk factor of this type of lymphoma
Witkowska M, Smolewski P. Helicobacter pylori infection, Chrinic Inflammation, and Genomic Transformations in Gastric MALT Lymphoma. Mediators of Inflammation :523170

6. Figure 1: Micrograph showing H. pylori with unipolar flagella
H.pylori infection
Caused by a gram negative, spiral bacteria
Once it colonises the stomach, it remains there for a lifetime, causing chronic inflammation, unless it is treated
Bacteria is present in 85-92% of patients with MALT lymphoma
In 80% of cases patients are
asymptomatic
Witkowska M, Smolewski P. Helicobacter pylori infection, Chrinic Inflammation, and Genomic Transformations in Gastric MALT Lymphoma. Mediators of Inflammation :523170
Kim S.S, Ruiz V.E, Carroll, J.D, Moss, S.F. Helicobacter pylori in the pathogenesis of gastric cancer and gastric lymphoma. Cancer Letters. 2012; 305(2):
Figure 1: Micrograph showing H. pylori with unipolar flagella

7. How does H.pylori contribute to MALT Lymphoma?
1. Persisting presence of H.pylori causes chronic inflammation
2. Inflammation leads to infiltration of immune cells in order to remove the microorganism
- B and T lymphocytes – production of antibodies
- Macrophages –production of APRIL
- Neutophils – production of reactive oxygen species
3. Reactive oxygen species cause damage to the DNA of B-lymphocytes
4. May lead to overexpression of oncogenes or alteration of signalling pathways
Pereira M I, Medeiros J.A. Role of Helicobacter Pylori in gastric mucosa-associated lymphoid tissue lymphomas. World J Gastroenterol. 3014; 20(3)

8. Detection of MALT lymphoma
Diagnosis is based on various tests
Endoscopy with biopsy– investigation of any changes to the stomach lining and obtaining a tissue sample where appropriate
Histology Investigation– Routine histology Immunohistochemistry (positive for CD20,coexpression of CD 43/ BLC Negative for CD5 CD10,CD 23, cyclin D1)
Cytogenetic and Molecular Tests - to investigate genetic aberrations, especially t(11;18) (q21;q21) translocation using methods like FISH or PCR
If histology results are negative for H.pylori, further tests are required:
Rapid Urea Breath Test
Blood tests
Faecal Test
Witkowska M, Smolewski P. Helicobacter pylori infection, Chrinic Inflammation, and Genomic Transformations in Gastric MALT Lymphoma. Mediators of Inflammation :523170
Pereira M I, Medeiros J.A. Role of Helicobacter Pylori in gastric mucosa-associated lymphoid tissue lymphomas. World J Gastroenterol. 3014; 20(3)

9. Endoscopy
Figure 2: Pictures showing different appearances of gastric MALT Lymphoma investigated using endoscope

10. B: Positive immunohistochemistry stain using CD20
Histology
Figure 3: Images showing Histology tissue architecture of gastric MALT lymphoma
A: H and E stain
B: Positive immunohistochemistry stain using CD20

11. Treatment
Treatment is based on the presence/ absence of H.pylori, invasion stage, age, nodal status, etc.
Many successful treatments are available:
Eradication of H.pylori First line treatment is H.pylori Used in low grades MALT lymphomas with a big success
Radiotherapy
Chemotherapy
Surgery
Immunotherapy
Witkowska M, Smolewski P. Helicobacter pylori infection, Chrinic Inflammation, and Genomic Transformations in Gastric MALT Lymphoma. Mediators of Inflammation :523170

12. H.Pylori Eradication
Eradication is usually a dual or triple therapy which uses a combination of proton pump inhibitor and antibiotics.
1. Proton pump inhibitor
Causes reduction of secretion of acids in the stomach
Esomeprazole, Lansoprazole, Omeptazole
2. Antibiotics
Combination of 2 or 3 antibiotics are used
Metronidazole and Clarithromycin or
Amoxicillin + Clarithromycin
3. Bismuth
Has similar effects as iron deprivation
Zullo A, Hassan C, Ridola L, Repici A, Manta R, AndianiA. Gastric MALT lymphoma:old and new insights. Annals of Gastroenterology. 2014; 27(1): 27–33.
Bland MV, Ismail S, Heinemann JA, Keenan JI. The action of bismuth against Helicobacter pylori Mimics but is not caused by intracellular iron deprivation. Antimicrobial Agents and Chemotherapy. 2004; 48(6):

13. H.Pylori Eradication
After treatment 8/10 patients experiencing regression of the cancer
Therapy is administrated usually for 1- 2 weeks
Successful if
Tumour hasn’t spread into the stomach wall
Tumour is absent in the lymph nodes
H.pylori is not resistant to antibiotics
Patient is t(11;18) negative
Zullo A, Hassan C, Ridola L, Repici A, Manta R, AndianiA. Gastric MALT lymphoma:old and new insights. Annals of Gastroenterology. 2014; 27(1): 27–33.

14. Summary
There’s strong evidence that H. pylori is strongly linked with Gastric lymphomas - especially with MALT lymphoma
Most important risk of developing gastric lymphoma is H.pylori infection
Many Tests are available to diagnose this cancer
Treatment has very high successful rate, currently new treatment using antibodies is under investigatigation