| Abstract|| |
Background: Upper gastrointestinal cancer particularly of stomach is a relatively frequent form of cancer. Gastric H pylori infection has been implicated in the pathogenesis of both gastric carcinoma and gastric lymphoma. Gastric carcinoma has been addressed by many articles in the Kingdom of Saudi Arabia (KSA) and the Middle East, while only a few addressed gastric lymphoma.
Aim of the study: To investigate the relative frequency of gastric carcinoma and gastric lymphoma and their association with H pylori infection in endoscoped patients.
Patients and methods: A retrospective study of patients endoscoped at King Fahad Hospital of the University, Al-Khobar, KSA during the period 1983-1999 was performed. Endoscopy and pathology records were retrieved and reviewed. The histopathology slides were re-examined, applying immunohistochemical techniques on corresponding paraffin sections to classify the various tumors. H pylori were identified on routine histology and by utilizing Giemsa stain.
Results: During the study period of 17 years (1983-1999), a total of 94 endoscopically-diagnosed, histologically-confirmed cases of gastric malignancy were identified. Of these, there were 55 gastric adenocarcinoma and 39 gastric lymphoma. H pylori was identified in the adjacent gastric mucosa in 18 of all cases of gastric adenocarcinoma and in 27 of the 39 cases of lymphoma.
Conclusion: The study demonstrates the comparatively high frequency of gastric lymphoma in this population and confirms the intimate association of H-pylori infection to both gastric adenocarcinoma and MALT-lymphoma. Gastric lymphoma should always be considered in the differential diagnosis of gastric malignancy and the use of immunohistochemistry is essential for the differential diagnosis of some of these tumors
Keywords: Gastric adenocarcinoma, lymphoma, H. pylori, etiology.
|How to cite this article:|
Satti MB, Al-Quorain AA, Al-Gindan YM, Al Hamdan AA, Al-Idrissi HY. Gastric malignancy : Clinicopathologic spectrum and relationship to helicobacter pylori infection. Saudi J Gastroenterol 2005;11:149-56
|How to cite this URL:|
Satti MB, Al-Quorain AA, Al-Gindan YM, Al Hamdan AA, Al-Idrissi HY. Gastric malignancy : Clinicopathologic spectrum and relationship to helicobacter pylori infection. Saudi J Gastroenterol [serial online] 2005 [cited 2020 Nov 24];11:149-56. Available from: https://www.saudijgastro.com/text.asp?2005/11/3/149/33318
Adenocarcinoma of the stomach is second only to lung cancer as the leading cause of cancer death worldwide .
It has a striking variable incidence that generally parallels the epidemiology of H pylori infection  . Gastric lymphoma accounts for about 5% of gastric neoplasms in Western studies but it is the most common of gastrointestinal lymphomas. The relationship between gastric lymphoma and H pylori has been demonstrated in a number of epidemiologic  and case control studies  . Furthermore, it has been shown that gastric lymphoma is clearly associated with chronic gastritis in that 80% of gastric lymphoma develop in patients with chronic gastritis  . The concept of mucosa-associated lymphoid tissue (MALT) was first characterized in 1983 by Isaacson and Wright  , followed by other studies implicating H pylori in the pathogenesis of chronic gastritis and MALT lymphoma ,,. In KSA and the Gulf region, a number of studies reported gastric carcinoma among the top ranked cancers ,,,,,,, . On the contrary to this, is the lack of literature addressing the relative frequency of gastric lymphoma ,. Numerous reports from KSA and the Gulf region addressed the prevalence of H pylori and gastritis utilizing various identification methods ,,,,,, . On this background, we undertook this study to determine on a wide scale long duration, the relative frequency of endoscopically-diagnosed lymphomas and gastric carcinoma with particular emphasis on the relationship to H pylori and investigate their clinical and demographic differences and similarities.
| Patients and methods|| |
This is a retrospective clinicopathologic study of cases of gastric malignancy diagnosed on upper gastrointestinal endoscopy and biopsy at King Fahad Hospital of the University (KFHU), Al Khobar, KSA, during the period 19831999. Cases were retrieved from histopathology records, medical records and endoscopy records. Medical and endoscopy records were reviewed for demographic data, symptoms/signs, relevant laboratory data and for site and gross morphology of lesions on endoscopy. Histopathology H&E-stained sections of biopsy material were reviewed and the corresponding paraffin blocks were retrieved. Sections were cut and stained for the identification of mucin using D-PAS and mucicarmine. H. pylori were searched for in the surface mucus layer of H&E stained sections and confirmed by the Giemsa stain as blue curved rods [Figure. 1] a. The H&E was also used to classify gastric malignancy into adenocarcinoma, intestinal type [Figure. 1] b and adenocarcinoma mucus cell (signet ring) type [Figure - 1] c, d An immunohistochemical panel of antibodies was used applying the standard immunoperoxidase , . technique with microwave antigen retrieval, including LCA (Leukocyte Common Antigen) 1:100, CK (Cytokeratin) 1:100, EMA (Epithelial Membrane Antigen) 1:100, CD20 (B cells) 1:100, UCHL1 (T cells) 1:200, Vimentin 1:800, CD30 1:50 and CD15 1:50 dilution. Antibodies used from Dako-cytomation from Denmark.
| Results|| |
[Table - 1] shows the demographic and clinical data of patients with gastric malignancy. While there is no difference in sex ratio for patients with gastric lymphoma, males outnumbered females by 2:1 in patients with gastric carcinoma. Both involved a wide age range with a respective mean of 57 years and 51 years for carcinoma and lymphoma. There is no difference in symptoms duration or other clinical symptoms or signs except for jaundice and ascites that indicated metastatic disease more common in patients with carcinoma. The tumor involved the antrum in 90% of cases of lymphomas and in 60% of cases of carcinoma. [Table - 2] shows the rate of H. pylori identification in tissue sections of gastric mucosa on H&E and Giemsa stains. Eighteen (33%) of 55 patients with gastric carcinoma were positive for H. pylori. When related to the subtype of gastric adenocarcinoma ten (37%) of 27 intestinal type adenocarcinoma were positive compared to eight (29%) of 28 mucus cell type adenocarcinoma. [Table - 3], demonstrates H. pylori identification in gastric mucosa of lymphoma patients. Twenty-seven (69%) of 39 patients with gastric lymphoma are positive for H pylori. When related to the subtype of lymphoma, the rate was highest (88%) in MALT lymphoma low grade, followed by MALT lymphoma, high grade (68%). No H pylori were identified in any of the three patients of anaplastic large cell lymphoma (ALCL) or the one case with T-cell lymphoma. Immunohistochemistry was extremely useful in the differential diagnosis of difficult cases and confirmatory for carcinoma in 11 patients (20%), where signet ring cells were not obvious [Figure - 2]. The diagnosis of MALT lymphoma was characterized by lymphoepithelial lesions and small centrocyte-like B cells in the low-grade type [Figure - 3] and larger cells with vesicular nuclei in the MALT lymphoma high grade [Figure - 4]. The panel of antibodies was extremely useful for the confirmation of the diagnosis of T cell lymphoma and the CD30 (Kil) positive ALCL [Figure - 5].
| Discussion|| |
Adenocarcinoma of the stomach is second only to lung cancer as the leading cause of cancer death worldwide  . Its incidence however is quite variable and generally parallels the epidemiology of H. pylori infection and remains a disease of poverty, more prevalent in under developed nations with death rates of over 50/100,000 in some parts of Central America  compared to a death rate of 6/100,000 in the USA. Gastric lymphoma accounts for about 5% of gastric neoplasms in Western studies, but it is the most common gastrointestinal lymphoma. The relationship between gastric lymphoma and H. pylori has been demonstrated in a number of epidemiologic  and case control studies . Furthermore, it has been shown that gastric lymphoma is clearly associated with chronic gastritis; that 80% of gastric lymphomas develop in patients with chronic gastritis  . Mucosa associated lymphoid tissue (MALT) lymphoma was first characterized by Isaacson and Wright  in 1983, and found to be unlike "classic" nodal lymphomas. Mucosa associated lymphoid tissue lymphoma represents approximately 50% of primary gastric lymphomas  . Mucosa associated lymphoid tissue is not found in the healthy gastric mucosa. Lymphoid follicles in the gastric mucosa however, were found to be a common and specific feature of H. pylori gastritis suggesting that the lymphoid hyperplasia was the result of bacterial antigenic stimulation  . Wotherspoon et al noted that some patients with H. pylori associated lymphoid follicles demonstrated B-cells infiltrating into gastric epithelium (lymphoepithelial lesions), consistent with gastric MALT lymphoma  . In such patients H. pylori was present in 92% of the samples. However, the differentiation of early low-grade gastric MALT lymphoma from lymphoid hyperplasia is critical to patients' management. Most MALT lymphomas express monotypic immunoglobulin and are therefore monoclonal B-cells. Immunohistochemical demonstration of light chain restriction by the centrocyte-like cells and monoclonal IgG gene re-arrangement are essential to the diagnosis. Both low and high-grade gastric MALT lymphoma is associated with H. pylori infection 
There are many reports addressing cancer and gastrointestinal malignancy in KSA and the Gulf states. The relative frequency of gastrointestinal cancer and in particular gastric carcinoma varied, though both mostly ranked top or among the first few top-ranked cancers. In an earlier study from the Eastern province, gastrointestinal cancer was the most common constituting 25% of all cancers, whereas stomach cancer accounted for 7.7% of all sites and ranked third  . A similar result was obtained in another study where gastric carcinoma accounted for 19.6% of digestive system malignancies, second only to hepatocellular carcinoma  . In a study from Riyadh, gastrointestinal malignancy was the commonest accounting for 27.4% of all cancer cases reviewed from histopathology records. Of these gastric cancer accounted for 31%  . Gastric cancer ranked fourth with a relative frequency of 6.52 among both sexes in a study of 1196 cancer patients from Riyadh collected over a 5 year period  . In another study from Riyadh"  gastrointestinal cancer accounted for 25.5% of total cancer cases seen at King Khalid University Hospital. Of these cases, stomach cancer accounted for 18% second only to hepatocellular carcinoma at 34%. In an endoscopic retrospective study from Riyadh, gastric carcinoma accounted to 67 patients (0.62%) of a total 10,725 upper GI endoscopies over a 7-year period'  Furthermore in a study of 234 patients of primary GI malignancy from the Southern province of KSA, gastric carcinoma accounted for 27%, second only to hepatoma at 29%  . Similarly in a study from UAE, gastrointestinal cancer accounted for 31.5% of all 612 cancer patients diagnosed between 1981-1995 . Stomach cancer was the most common male malignancy (17.6%). Of relevance was the lack of literature addressing prevalence or existence of gastric lymphoma , . An apparently increasing form of gastric malignancy. Various studies on H. pylori, prevalence and associated gastroduodenal disease were published from KSA with variable prevalence Figureures. However, most studies confirmed the high prevalence rate of antral H. pylori, utilizing various identification methods ,,,,,, . In a study from Kuwait, the prevalence rate of H. pylori infection was 88.5% in an endoscopy study of 300 Kuwaiti patients  . In a study from Asir region, KSA, H. pylori was found in 84% of patients of intestinal type adenocarcinoma, and in 66.7% each of the diffuse type adenocarcinoma and gastric lymphoma  . These Figureures are slightly different from ours in that H. pylori was more prevalent in gastric MALT lymphoma (88%) compared to intestinal type adenocarcinoma at 37%, based on tissue biopsies. Our results confirm that gastric lymphoma is as common as adenocarcinoma in our population. Although gastric lymphoma occurs at a relatively younger age than carcinoma, it was not possible to confirm the diagnosis without a tissue biopsy. Furthermore, in poorly differentiated diffuse (mucus cell type) adenocarcinoma, immunohistochemistry using LCA, CK, EMA is invaluable to diagnosis [Figure - 2]. The use of other lymphoid markers and CD30 in anaplastic malignancy is essential for the diagnosis of ALCL and in excluding anaplastic carcinoma [Figure - 5]. Our results demonstrated the close link of H. pylori to gastric lymphoma and gastric carcinoma, where there was no difference between intestinal and mucus cell (diffuse) type adenocarcinoma. The apparent lower rate of H. Pylori compared to the gastritis and general population previously reported may be explained by the unfavorable environment created in the stomach by the gastric malignancy and the associated intestinal metaplasia  . In the Saudi National Cancer Registry, 738 patients of stomach cancers were seen among Saudis during the period 1994-96. These accounted for 4.5% of all diagnosed patients. The overall age specific incidence rate was 3.7/100,000 population. It ranked 6th among males and 10th among females. Of all patients only 5.7% were gastric lymphomas  . In an editorial article titled "It should be possible to eliminate peptic ulcer disease and gastric carcinoma from KSA", Graham et al  discussed the epidemiology and the cost effectiveness and ways to achieve this goal, mainly through effective eradication programs for H. pylori. Some prospective data suggest that between 35-89% of gastric cancer is related to H. pylori. The estimated mean interval between seropositivity for H. pylori and the development of cancer ranged from 6-14 years. The age of the patient at the time of onset of the infection has been considered a critical factor in the development of gastric cancer ,
In conclusion, our study demonstrates the comparatively high frequency of gastric lymphoma in this population and confirms the intimate association of H. pylori infection to both gastric adenocarcinoma and MALT-lymphoma. Gastric lymphoma involves a relatively younger age group compared to carcinoma with no significant sex difference. Gastric carcinoma however is more common in males (2:1) with significantly more of symptoms and signs of advanced disease. Gastric lymphoma however should always be considered in the differential diagnosis of gastric malignancy and the use of immunohistochemistry is essential for the differential diagnosis of some of these tumors.
This work has been supported by grant #1049 from King Faisal University, Dammam, Deanship of Research. We acknowledge the secretarial assistance of Mr. Ramesh Kumar and Ms Elena F Garana as well as the photographic help of Mr. John Myers.
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Mohamed Bakhiet Satti
Department of Pathology, King Abdulaziz Medical City, P 0 Box 9516, Jeddah 21423
Source of Support: None, Conflict of Interest: None
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1], [Table - 2], [Table - 3]