130
Views
2
CrossRef citations to date
0
Altmetric
Original Research

Association Between Gastric Lymphoid Follicles (Precursor Of MALT Lymphomas) And H. pylori Infection At A Referral Hospital In Iran

, , , , &
Pages 409-413 | Published online: 29 Oct 2019

Abstract

Purpose

Mucosa-associated lymphoid tissue (MALT) is the most common endoscopic finding in Helicobacter pylori positive patients that can progress to MALT lymphoma after a prolonged antigenic contact. This study was aimed to evaluate the prevalence of lymphoid follicles and aggregates (precursors of MALT lymphomas) in gastric mucosal biopsies and their correlation with H. pylori infection.

Patients and methods

In this study, 100 patients who had undergone an upper gastrointestinal endoscopy were enrolled. Five biopsy specimens were taken each patient through screening endoscopy and histopathological changes were evaluated and graded using the Wotherspoon System. The clinical background and H. pylori infection status were also investigated.

Results

Among the 100 cases in our series, 79 patients (79%) showed evidence of MALT in at least one biopsy specimen taken from the stomach and 21 cases (21%) had no evidence of MALT. H. pylori infection was detected in 74 (74%) patients. Lymphoid follicles were detected more frequently in H. pylori-positive patients (59%) compared to H. pylori-negative cases (3%) (P<0.001).

Conclusion

The frequency of lymphoid follicles and aggregates in gastric mucosal is associated with H. pylori infection. Further community-based studies in larger sample sizes using a combination of microscopic methods and PCR assay are required for effective monitoring of H. pylori infection.

Introduction

Helicobacter pylori (H. pylori) is a spiral, gram-negative bacterium that causes chronic gastritis, peptic ulcer disease and is associated with the development of gastric cancer.Citation1 Its prevalence is about 4.4 billion individuals in worldwide, affecting more than half of the world’s population.Citation2 Chronic infection of the stomach by H. pylori is being increasingly recognized as a precursor of mucosa-associated lymphoid tissue (MALT) lymphoma.Citation3 Gastric cancer is the fifth most common cancer. It is that estimated about one million new cases and 783,000 related deaths occur every year.Citation4 Gastric MALT lymphoma accounts for only 1-6% of all gastric malignancies and about 50% of primary gastric lymphomas.Citation5

H. pylori infection serves as an antigenic driver that can activate innate immune system. As a result of this phenomenon, the immune and gastric epithelial cells respond by the secretion antimicrobial peptides and cytokines (pro- and anti-inflammatory).Citation6 Immune response accelerates the formation of lymphoid follicles in the gastric mucosa.Citation6 This statement is supported by the fact that about 75% of low-grade gastric MALT lymphoma can be improved by eradication of H pylori infection with antibiotic therapy.Citation7

Mucosa-associated lymphoid tissue (MALT) lymphoma is defined as an extranodal low-grade marginal zone B cell lymphomas.Citation8 Although the stomach is the most common site of MALT lymphomas, it in healthy individuals does not have organized or diffuses lymphoid tissue.Citation9 Symptoms associated with gastric MALT lymphoma are generally non-specific and signs including dyspepsia, vague epigastric pain, bloating and heartburn; anemia, melena as well as hematemesis are common in this disease.Citation10 The clinical diagnosis of gastric MALT lymphoma depends largely on clinical symptoms, endoscopic examination and histopathologic finding of gastric biopsy tissue.Citation10

Studies have shown that the incidence of gastric cancer in Iran, unlike developed countries, has increased over the past 30 years.Citation11,Citation12 This study was designed to determine the prevalence of gastric lymphoid follicles and aggregates (precursors of MALT lymphomas) in gastric mucosal biopsies and evaluate its correlation with H. pylori infection.

Materials And Methods

This cross-sectional study was conducted in 100 consecutive patients admitted to Imam Reza Hospital (a referral center affiliated with Kermanshah University of Medical Sciences) Kermanshah, Iran for endoscopic screening. Five biopsy specimens were taken from each patient through endoscopy (1 from incisura angularis, 2 from antrum, lesser and greater curvature and 2 from cardia, lesser and greater curvature). Biopsy specimens were fixed in 10% formalin and embedded in paraffin. Then, 4-µm paraffin sections were stained with hematoxylin and eosin and Giemsa. All the available slides were evaluated for the presence of lymphoid aggregates, lymphoid follicles and other pathological changes in gastric mucosa by two pathologists, independently. The Wotherspoon scoring system was used for scoring gastric lymphoid infiltrates. Based on the histological scoring system of the Wotherspoon, a score of 2 or less is categorized as benign gastritis and a score of 3 or 4 represents suspicious MALT lymphoma cases.Citation13

To detect the presence of H. pylori, all biopsy specimens were evaluated by rapid urease test and Gram staining. Patients were considered positive for H. pylori if it was detected on histological and/or bacteriological examination. Exclusion criteria were a history of H. pylori eradication, a history of consumption of proton pump inhibitors (PPIs), H2-receptor blockers or antibiotics within 2 weeks prior to endoscopy and a history of gastric surgery or gastric neoplasms.

Associations between categorical variables were evaluated with Chi-squared test and Fisher’s exact test. The P < 0.05 was considered as statistically significant.

Results

This study was conducted in 40 men and 60 women aged 22–62 years old (median: 49 years). The distribution of biopsy specimens according to the histological score in each gastric region is summarized in . Seventy-nine patients (79%) showed evidence the presence of MALT in at least one biopsy specimen taken from the stomach and 21 cases (21%) had no evidence of MALT.

Table 1 Frequency Of Graded Histological Variables In Patients Admitted To Imam Reza Hospital, Kermanshah, Iran

Overall, H. pylori was detected in 74 (74%) patients. The relationship between mucosa-associated lymphoid tissue and H. pylori infection is shown in , indicating that 71% of the patients with mucosa-associated lymphoid tissue had H. pylori infection as opposed to 8% of them who did not (P<0.001). Additionally, lymphoid follicles were detected more frequently in H. pylori-positive patients (59%) compared to H. pylori-negative cases (3%) ().

Table 2 The Distribution Of Helicobacter pylori According To Presence Lymphoid Follicles And Lymphoid Aggregate

Table 3 Histological Grading Of All Biopsies In Relation To The Presence Of Helicobacter pylori

Discussion

This study evaluated the prevalence of lymphoid follicles and aggregates (precursors of MALT lymphomas) in gastric mucosal biopsies and correlates them with H. pylori infection at a referral hospital in the western part of Iran. MALT lymphomas are non-Hodgkins B-cell neoplasms derived from lymphoid aggregates in the lamina propria.Citation8 According to previous reports, lymphoid follicles and aggregates in the gastric mucosa are a specific the immune response to H. pylori.Citation14 This organism serves as an antigenic driver that can activate the immune system and accelerate lymphoid follicles proliferation in the gastric mucosa.Citation6

In the present study, the prevalence of H. pylori infection was 74%. The prevalence of H. pylori ranges from 15.1% to 87.7% in previous publications depending on the socioeconomic status, hygiene and sanitary conditions.Citation15 Improvements in these factors lead to a decrease in the prevalence of H. pylori and consequently in the peptic ulcer disease. The host immune response, especially the functionality of cytotoxic T-cells (killer T-cells), plays a key role in the outcome of H. pylori infection.Citation14 Although half of the world’s population is infected with this bacterium, only about 3% of all H. pylori infected subjects present with gastric adenocarcinoma.Citation16 Some reports have described that H. pylori cagA-positive strains have enhanced pathogenicity by stimulating cell transformation.Citation17

Iran is one of the largest developing countries in the Middle East with highly diverse dietary factors, lifestyle preferences, socioeconomic and hygiene conditions. According to the 2012 Census results, Iran has a population of 80.28 million and about one-third of the population lives below the national poverty line.Citation18 In a study conducted by Solimany et al, findings indicated a growing rate of gastric malignancy incidence in Kermanshah Province, where we carried out this study.Citation19 The clinical diagnosis of gastric MALT lymphoma depends largely on clinical symptoms, endoscopic examination and histopathologic finding of gastric biopsy tissue.Citation10 Countries with high incidence of gastric cancer, such as Japan and South Korea, have implemented gastric cancer screening programs using endoscopy for several decades.Citation20,Citation21 During the last years, endoscopy has been widely used as a part of health screening. However, few studies have reported some side effects for endoscopic screening, such as infections, false-positive results, and overdiagnosis.Citation22 Although upper gastrointestinal endoscopy is an invasive procedure, further evaluation of the impact of endoscopic screening is needed regarding the balance of cost and mortality reduction.

Fakhro et al found that the prevalence of lymphoid follicles and aggregates was 31.4% and 24.5% in gastric biopsy specimens in patients with dyspepsia, respectively.Citation23 Also, authors reported that the odds ratio of developing lymphoid follicles in H. pylori-positive patients compared to H. pylori-negative cases was 11:1. Kalebi et al found that the prevalence of lymphoid follicles was 11% among adult patients seen at a referral hospital in Kenya and all these patients had H pylori infection.Citation24 Garg et al also reported that there are lymphoid aggregates and lymphoid follicles in 25% and 19% of subjects, respectively.Citation25 In our study, prevalence of lymphoid follicles and aggregates in gastric mucosa in patients with H. pylori infection was 62% and 38%, respectively and lymphoid follicles were detected more frequently in H. pylori-positive patients (59%) compared to H. pylori-negative cases (3%) (P<0.001). The differences in prevalence can be explained by differences in the number and site of biopsy specimens, methods of H. pylori detection, and study populations. Furthermore, the bacterial load in biopsy specimens is generally low and irregular.Citation26 It appears that prevalence of lymphoid follicles and aggregates in oxyntic mucosa (14.8–44.0%) is lower than antral mucosa.Citation27

Previous studies showed that H. pylori is associated with an increased risk of gastric adenocarcinomas.Citation28,Citation29 Persistent inflammation of the stomach by H. pylori leads to the transition from normal mucosa to chronic superficial gastritis which may then progress to atrophic gastritis and intestinal metaplasia, and eventually to dysplasia and adenocarcinoma.Citation28,Citation29 There is no evidence to support the association between atrophic gastritis and gastric lymphoma.Citation30 Although both gastric adenocarcinomas and MALT lymphomas occur as a consequence of chronic gastric inflammation, differentiating them from each other is important because the prognosis and treatment options differ.

Conclusion

Our findings showed that the formation of gastric lymphoid follicles and aggregates significantly correlated with H. pylori infection. Early diagnosis and eradication of H. pylori infection in suspicious MALT lymphomas detected via histopathological evaluation will improve the patient’s quality of life and possibly prevent gastric cancer. Further community-based studies in larger sample sizes using a combination of microscopic methods and PCR assay are required for effective monitoring of H. pylori infection.

Ethics Approval And Consent To Participate

All the participants provided written informed consent prior to the study and this study was conducted in accordance with the Declaration of Helsinki. The protocol was approved by the Mashhad University of Medical Sciences Ethics Committee (8103907).

Data Sharing Statement

The data sets used and/or analyzed during this study are available from the corresponding author on reasonable request and were received permission for use by the Mashhad University of Medical Sciences Ethics Committee.

Acknowledgments

The authors want to thank their colleagues in Imam Reza Therapeutic Educational hospital of Kermanshah, Iran for their contribution to the patient’s diagnosis. This study was funded by Mashhad University of Medical Sciences, Mashhad, Iran (No code: 2127).

Disclosure

The authors report no conflicts of interest in this work.

References

  • Alfarouk KO, Bashir AH, Aljarbou AN, et al. The possible role of Helicobacter pylori in gastric cancer and its management. Front Oncol. 2019;9:75. doi:10.3389/fonc.2019.0007530854333
  • Hooi JK, Lai WY, Ng WK, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017;153(2):420–429. doi:10.1053/j.gastro.2017.04.02228456631
  • Floch P, Mégraud F, Lehours P. Helicobacter pylori strains and gastric MALT lymphoma. Toxins. 2017;9(4):132. doi:10.3390/toxins9040132
  • Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26–38. doi:10.5114/pg.2018.8000130944675
  • Nakamura S, Matsumoto T. Gastrointestinal lymphoma: recent advances in diagnosis and treatment. Digestion. 2013;87(3):182–188. doi:10.1159/00035005123635497
  • Chmiela M, Karwowska Z, Gonciarz W, Allushi B, Stączek P. Host pathogen interactions in Helicobacter pylori related gastric cancer. World J Gastroenterol. 2017;23(9):1521–1540. doi:10.3748/wjg.v23.i9.152128321154
  • Zullo A, Hassan C, Cristofari F, et al. Effects of Helicobacter pylori eradication on early stage gastric mucosa–associated lymphoid tissue lymphoma. Clin Gastroenterol Hepatol. 2010;8(2):105–110. doi:10.1016/j.cgh.2009.07.01719631287
  • Bacon CM, Du M-Q, Dogan A. Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists. J Clin Pathol. 2007;60(4):361–372. doi:10.1136/jcp.2005.03114616950858
  • Isaacson PG, Du MQ. Gastrointestinal lymphoma: where morphology meets molecular biology. J Pathol. 2005;205(2):255–274. doi:10.1002/path.170315643667
  • Hu Q, Zhang Y, Zhang X, Fu K. Gastric mucosa-associated lymphoid tissue lymphoma and Helicobacter pylori infection: a review of current diagnosis and management. Biomark Res. 2016;4:15. doi:10.1186/s40364-016-0068-127468353
  • Jenabi E, Saatchi M, Khazaei S, et al. National distribution of stomach cancer incidence in Iran: a population-based study. Adv Hum Biol. 2019;9(1):89–93. doi:10.4103/AIHB.AIHB_37_18
  • Rahimi F, Heidari M. Time trend analysis of stomach cancer incidence in the west of Iran. J Health Dev. 2012;1(2):100–111.
  • Wotherspoon AC, Diss T, Pan L, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993;342(8871):575–577. doi:10.1016/0140-6736(93)91409-f8102719
  • Kuo S-H, Cheng A-L. Helicobacter pylori and mucosa-associated lymphoid tissue: what’s new. Hematology Am Soc Hematol Educ Program. 2013;2013(1):109–117. doi:10.1182/asheducation-2013.1.10924319171
  • Toscano EP, Madeira FF, Dutra-Rulli MP, et al. Epidemiological and clinical-pathological aspects of Helicobacter pylori infection in brazilian children and adults. Gastroenterol Res Pract. 2018;2018:8454125. doi:10.1155/2018/845412530254670
  • Correa P, Piazuelo MB. Helicobacter pylori infection and gastric adenocarcinoma. US Gastroenterol Hepatol Rev. 2011;7(1):59–64.21857882
  • Kalaf EA, Al-Khafaji ZM, Yassen NY, Al-Abbudi FA, Sadwen SN. Study of the cytoxin-associated gene a (CagA gene) in Helicobacter pylori using gastric biopsies of Iraqi patients. Saudi J Gastroenterol. 2013;19(2):69–74. doi:10.4103/1319-3767.10847423481132
  • Statistical Centre of Iran. Summary and statistical report of the 2012 population and housing census. Tehran: Population census commission Mazandaran Province: population census commission Amol County 2012. doi:10.1094/PDIS-11-11-0999-PDN
  • Solimany A, Khoramdad M, Khademi N, Delpisheh A. Spatio-temporal study of gastric cancer incidence in Kermanshah Province, Iran during the years 2009–2014. Asian Pac J Cancer Prev. 2018;19(10):2871–2876. doi:10.22034/APJCP.2018.19.10.287130362315
  • Chung SJ, Park MJ, Kang SJ, et al. Effect of annual endoscopic screening on clinicopathologic characteristics and treatment modality of gastric cancer in a high‐incidence region of Korea. Int J Cancer. 2012;131(10):2376–2384. doi:10.1002/ijc.2750122362223
  • Choi KS, Jun JK, Lee HY, et al. Performance of gastric cancer screening by endoscopy testing through the National Cancer Screening Program of Korea. Cancer Sci. 2011;102(8):1559–1564. doi:10.1111/j.1349-7006.2011.01982.x21564421
  • Hamashima C. Benefits and harms of endoscopic screening for gastric cancer. World J Gastroenterol. 2016;22(28):6385–6392. doi:10.3748/wjg.v22.i28.638527605874
  • Fakhro ARE, Bahaa El Din AF, Farid IMA, Jamsheer HM. The association between Helicobacter pylori infection and lymphoid reaction in patients suffering from dyspepsia in Bahrain. Saudi J Gastroenterol. 1999;5(3):129–133.19864738
  • Kalebi A, Rana F, Mwanda W, Lule G, Hale M. Histopathological profile of gastritis in adult patients seen at a referral hospital in Kenya. World J Gastroenterol. 2007;13(30):4117–4121. doi:10.3748/wjg.v13.i30.411717696233
  • Garg B, Sandhu V, Sood N, Sood A, Malhotra V. Histopathological analysis of chronic gastritis and correlation of pathological features with each other and with endoscopic findings. Pol J Pathol. 2012;63(3):172–178.23161233
  • Pokhrel N, Khanal B, Rai K, Subedi M, Bhattarai NR. Application of PCR and microscopy to detect Helicobacter pylori in gastric biopsy specimen among acid peptic disorders at tertiary care centre in Eastern Nepal. Can J Infect Dis Med Microbiol. 2019;2019. doi:10.1155/2019/3695307
  • Zaitoun A. The prevalence of lymphoid follicles in Helicobacter pylori associated gastritis in patients with ulcers and non-ulcer dyspepsia. J Clin Pathol. 1995;48(4):325–329. doi:10.1136/jcp.48.4.3257615851
  • Ishaq S, Nunn L. Helicobacter pylori and gastric cancer: a state of the art review. Gastroenterol Hepatol Bed Bench. 2015;8(Suppl 1):S6–S14.26171139
  • Díaz P, Valenzuela Valderrama M, Bravo J, Quest AFG. Helicobacter pylori and gastric cancer: adaptive cellular mechanisms involved in disease progression. Front Microbiol. 2018;9:5. doi:10.3389/fmicb.2018.0000529403459
  • Ishikura N, Usui Y, Ito H, et al. Helicobacter pylori (HP) infection alone, but not HP-induced atrophic gastritis, increases the risk of gastric lymphoma: a case-control study in Japan. Ann Hematol. 2019;98(8):1981–1987. doi:10.1007/s00277-019-03721-y31177299