Malt lymphoma as a cause of acute gastric bleeding

Reprinted from 8th WORLD CONGRESS OF THE INTERNATIONAL GASTRO-SURGICAL CLUB (Strazbur, France, April 15-18, 1998.)

S.Šutulović, T. Milosavljević, P.Peško and M. Micev

Regional Hospital, Bor
Clinical Center of Serbia, Beograd (YU)

INTRODUCTION

Helicobacter pylori has been associated to the development of mucosa-associated lymphoid tissue (MALT), and epidemiological data support the principal pathogenic role of H. pylori in the development of MALT lymphoma (1).

Tumors of the stomach can cause acute gastrointestinal hemorrhage, but they very rarely account for 2 to 4 per cent of such causes and most are gastric cancers. MALT lymphoma can also be rarely manifested by acute upper gastrointestinal hemorrhage (7).

The aim of our report was to present a patient with uncommon acute hemorrhage of the stomach due to low-grade MALT lymphoma.

CASE REPORT

We report the patient M.Z., aged 33 worker, lives in a village. Came to the Regional Hospital because of hematemesis. Anamnestically, the patient had periodical dull epigastric pains in the previous years, and he took, on his own, antacid and H2 receptor antagonists. Within the last ten days the difficulties worsened and suddenly the patient started vomiting fresh blood. Hematemesis stopped after he was treated conservatively. After the upper gastrointestinal endoscopy was effected, he was suspected to have ulcerative gastric cancer in the distal part of the minor gastric curve, and he was sent to the Clinical Center for further treatment. Immediately after admission to the Clinic, the upper gastrointestinal endoscopy was repeated, with biopsy. Endoscopic finding: an ulceration of 10 x10 mm diameter with wider rigid area, and no peristalsis, on incisura angularis of the minor curve. The antral part of the stomach was without pathologic changes. The pylorus is passable. Duodenum was regular.
A rapid urease test was strongly positive. The preparation was colored within 30 minutes. The complete laboratory analysis resulted to be regular (excepting anemia), as well as ultrasound checkup of the upper abdomen.

Because of strong hematemesis which occurred within 24 hours, it has been proceeded to surgical intervention since endoscopic hemostatis was unsuccessfull. The following was performed: Resectio ventriculi subtotalis. Gastroenteroanastomosis Roux-en-Y, sutura duodeni terminalis cum stapler TA 30, drainage cavi subhepatici (Figure 1).

A histological examination both of the biopsy specimens and of the resected stomach gave the following results: microscopically, massive lymphoid infiltration surrounding the ulceration and erosions confined to slightly fibrotic mucosa and submucosa, including reactive non-neoplastic follicles. On close inspection, the neoplastic cells infiltrated around the follicles in the marginal zone regions spreading out into surrounding areas of mucosa and deeply in submucosa . Characteristic presence of so-called lymphoepithealial lesion as well as described follicular coloniyation indicate a possible neoplastic lymphoid infiltration.

Peritumoral mucosa showed severe chronic inflammatory changes, sometimes with an aspect of active "follicular gastritis" and severe Helicobacter pylori colonization. Surface cytoplasmic immunoglobulin expression with kappa light chainrestriction was proved on CCL B-cells of examined lymphoid proliferation. Subsequently, these cells show to be both CD5 and CD10 negative, but they expressed Bcl-2 protein. The diagnosis of low-grade B-cell gastric lumphoma of MALT type was achieved (Figure 2).

The patient has been treated by eradicatio trypli therapy (Omeprazol, Methronidazol, Amoxicillyn). Upper gastrointestinal endoscopy was further perfomed both after a month and six months from operation. In both cases, findings were satisfactory and H.pylori was not identified.

DISCUSSION

Helicobacter pylori exposure has been associated with several gastrointestinal neoplasms including gastric adenocarcinoma, non-Hodgkin lymphoma, MALT lumphoma and colon polyps. It is the class I carcinogen (5).

The presence of MALT lymphoma in the stomach is indicative for H.pylori infection: chronic H.pylori infection is associated with B-cell hyperplasia, B-cell follicles with germinal centres within the gastric mucosa in addition to plasmocytosis (6). MALT lymphomas are characterized by a monoclonal B-cell population infiltrating the epithelium ("limphoepithelial lesion") by small cleaved or centrocyte-like cells with a smaller percentage of larger blasts also being present (6).

The exact mechanisms how H.pylori triggers the development of MALT lymphoma remain unknown.

Many studies show dramatic response of gastric MALT lymphoma to anti-H.pylori treatment, which suggests that H.pylori infection is closely related to the patogenesis of low-grade gastric MALT lymphoma, but only low-grade gastric MALT lymphoma have consistently responded to antibiotics (4).

The most common clinical features were abdominal pain, gastrointestinal bleeding, anorexia, vomiting and weight loss: perforation is not so rare, while acute gastrointestinal hemorrhage is not so often (4). In low-grade MALT lymphoma a weight loss and increased erytrocyte sedimentation rate were significantly less frequent when compared with high-grade lymphoma (2).

Low grade lymphoma endoscopic findings were often interpreted as benign and those of high-grade lymphoma were most frequently interpreted as carcinoma, while in our case the endoscopic finding suspected an ulternative carcinoma on the distal part of stomach's minor curve despite the fact that histological examination confirmed a low-grade MALT lymphoma(2).

Attention should be paid especially to the infiltrative type of gastric lymphoma which is difficult to diagnose and differentiate from other gastric conditions such as ulcers and erosions, but which is most often found at an early stage and has a better prognosis. Adequate pre-treatment staging is necessary and may indicate the need of more aggressive additional treatment (3).

CONCLUSION

MALT lymphoma has non-specific and pathognomonic endoscopic aspects, and the acute upper gastrointestinal hemorrhage could be the first clinical symptom of the disease.

BIBLIOGRAPHY

1. S.G.M. Meuwissen. R.J.Kuipers. Helicobacter pylori, gastric cancer and gastric lymphoma. Update Gastroenterology 1996; 57-65
2. B.G.Taal. H. Boot. P.Van Heerde, D. De Jong, A.A.Hart, J.M. Burgers, Primary non-Hodgkin lymphoma of the stomach: endoscopic pattern and prognosis in low versus high grade malignancy in relation to the MALT concept. Gut. 1996 Oct; 39(4): 556-61
3. E.Seifert, F.Schulte, J. Weissmuller, C.R.De Mas, M. Stolte. Endoscopic and bioptic diagnosis of malignant non-Hodgkin's lymphoma of the stomach. Endoscopy 1993 Oct; 25(8): 497-501.
4. I.P.Chaing, H.H.Wang, A.L.Cheng, J.T.Lin, I.J. Su. Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue: clinicopathologic analysis of 19 cases. J.-Formos-Med-Assoc.1996 Nov; 95(11): 857-65
5. Doglioni C.,Wothersproon A., Machini A.,De Boni M., Isaacson P. High incidence of primary gastric lymphoma in Northeastern Italy, Lancet 1992, 339,834-5
6. Genta RM, Hamner H W, Graham D. Gastric lymphoid follicles in Helicobacter -pylori infection. Hum Pathol 1993, 24:577-83
7. Cooper DL, Doria R, Salloum E. Primary gastrointestinal lymphomas. Gastroenterologist 1996. Mar: 4(1): 54-64

	Malt lymphoma as a cause of acute gastric bleeding Case reports
	Reprinted from 8th WORLD CONGRESS OF THE INTERNATIONAL GASTRO-SURGICAL CLUB (Strazbur, France, April 15-18, 1998.) S.Šutulović, T. Milosavljević, P.Peško and M. Micev Regional Hospital, Bor Clinical Center of Serbia, Beograd (YU) INTRODUCTION Helicobacter pylori has been associated to the development of mucosa-associated lymphoid tissue (MALT), and epidemiological data support the principal pathogenic role of H. pylori in the development of MALT lymphoma (1). Tumors of the stomach can cause acute gastrointestinal hemorrhage, but they very rarely account for 2 to 4 per cent of such causes and most are gastric cancers. MALT lymphoma can also be rarely manifested by acute upper gastrointestinal hemorrhage (7). The aim of our report was to present a patient with uncommon acute hemorrhage of the stomach due to low-grade MALT lymphoma. CASE REPORT We report the patient M.Z., aged 33 worker, lives in a village. Came to the Regional Hospital because of hematemesis. Anamnestically, the patient had periodical dull epigastric pains in the previous years, and he took, on his own, antacid and H2 receptor antagonists. Within the last ten days the difficulties worsened and suddenly the patient started vomiting fresh blood. Hematemesis stopped after he was treated conservatively. After the upper gastrointestinal endoscopy was effected, he was suspected to have ulcerative gastric cancer in the distal part of the minor gastric curve, and he was sent to the Clinical Center for further treatment. Immediately after admission to the Clinic, the upper gastrointestinal endoscopy was repeated, with biopsy. Endoscopic finding: an ulceration of 10 x10 mm diameter with wider rigid area, and no peristalsis, on incisura angularis of the minor curve. The antral part of the stomach was without pathologic changes. The pylorus is passable. Duodenum was regular. A rapid urease test was strongly positive. The preparation was colored within 30 minutes. The complete laboratory analysis resulted to be regular (excepting anemia), as well as ultrasound checkup of the upper abdomen. Because of strong hematemesis which occurred within 24 hours, it has been proceeded to surgical intervention since endoscopic hemostatis was unsuccessfull. The following was performed: Resectio ventriculi subtotalis. Gastroenteroanastomosis Roux-en-Y, sutura duodeni terminalis cum stapler TA 30, drainage cavi subhepatici (Figure 1). A histological examination both of the biopsy specimens and of the resected stomach gave the following results: microscopically, massive lymphoid infiltration surrounding the ulceration and erosions confined to slightly fibrotic mucosa and submucosa, including reactive non-neoplastic follicles. On close inspection, the neoplastic cells infiltrated around the follicles in the marginal zone regions spreading out into surrounding areas of mucosa and deeply in submucosa . Characteristic presence of so-called lymphoepithealial lesion as well as described follicular coloniyation indicate a possible neoplastic lymphoid infiltration. Peritumoral mucosa showed severe chronic inflammatory changes, sometimes with an aspect of active "follicular gastritis" and severe Helicobacter pylori colonization. Surface cytoplasmic immunoglobulin expression with kappa light chainrestriction was proved on CCL B-cells of examined lymphoid proliferation. Subsequently, these cells show to be both CD5 and CD10 negative, but they expressed Bcl-2 protein. The diagnosis of low-grade B-cell gastric lumphoma of MALT type was achieved (Figure 2). The patient has been treated by eradicatio trypli therapy (Omeprazol, Methronidazol, Amoxicillyn). Upper gastrointestinal endoscopy was further perfomed both after a month and six months from operation. In both cases, findings were satisfactory and H.pylori was not identified. DISCUSSION Helicobacter pylori exposure has been associated with several gastrointestinal neoplasms including gastric adenocarcinoma, non-Hodgkin lymphoma, MALT lumphoma and colon polyps. It is the class I carcinogen (5). The presence of MALT lymphoma in the stomach is indicative for H.pylori infection: chronic H.pylori infection is associated with B-cell hyperplasia, B-cell follicles with germinal centres within the gastric mucosa in addition to plasmocytosis (6). MALT lymphomas are characterized by a monoclonal B-cell population infiltrating the epithelium ("limphoepithelial lesion") by small cleaved or centrocyte-like cells with a smaller percentage of larger blasts also being present (6). The exact mechanisms how H.pylori triggers the development of MALT lymphoma remain unknown. Many studies show dramatic response of gastric MALT lymphoma to anti-H.pylori treatment, which suggests that H.pylori infection is closely related to the patogenesis of low-grade gastric MALT lymphoma, but only low-grade gastric MALT lymphoma have consistently responded to antibiotics (4). The most common clinical features were abdominal pain, gastrointestinal bleeding, anorexia, vomiting and weight loss: perforation is not so rare, while acute gastrointestinal hemorrhage is not so often (4). In low-grade MALT lymphoma a weight loss and increased erytrocyte sedimentation rate were significantly less frequent when compared with high-grade lymphoma (2). Low grade lymphoma endoscopic findings were often interpreted as benign and those of high-grade lymphoma were most frequently interpreted as carcinoma, while in our case the endoscopic finding suspected an ulternative carcinoma on the distal part of stomach's minor curve despite the fact that histological examination confirmed a low-grade MALT lymphoma(2). Attention should be paid especially to the infiltrative type of gastric lymphoma which is difficult to diagnose and differentiate from other gastric conditions such as ulcers and erosions, but which is most often found at an early stage and has a better prognosis. Adequate pre-treatment staging is necessary and may indicate the need of more aggressive additional treatment (3). CONCLUSION MALT lymphoma has non-specific and pathognomonic endoscopic aspects, and the acute upper gastrointestinal hemorrhage could be the first clinical symptom of the disease. BIBLIOGRAPHY 1. S.G.M. Meuwissen. R.J.Kuipers. Helicobacter pylori, gastric cancer and gastric lymphoma. Update Gastroenterology 1996; 57-65 2. B.G.Taal. H. Boot. P.Van Heerde, D. De Jong, A.A.Hart, J.M. Burgers, Primary non-Hodgkin lymphoma of the stomach: endoscopic pattern and prognosis in low versus high grade malignancy in relation to the MALT concept. Gut. 1996 Oct; 39(4): 556-61 3. E.Seifert, F.Schulte, J. Weissmuller, C.R.De Mas, M. Stolte. Endoscopic and bioptic diagnosis of malignant non-Hodgkin's lymphoma of the stomach. Endoscopy 1993 Oct; 25(8): 497-501. 4. I.P.Chaing, H.H.Wang, A.L.Cheng, J.T.Lin, I.J. Su. Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue: clinicopathologic analysis of 19 cases. J.-Formos-Med-Assoc.1996 Nov; 95(11): 857-65 5. Doglioni C.,Wothersproon A., Machini A.,De Boni M., Isaacson P. High incidence of primary gastric lymphoma in Northeastern Italy, Lancet 1992, 339,834-5 6. Genta RM, Hamner H W, Graham D. Gastric lymphoid follicles in Helicobacter -pylori infection. Hum Pathol 1993, 24:577-83 7. Cooper DL, Doria R, Salloum E. Primary gastrointestinal lymphomas. Gastroenterologist 1996. Mar: 4(1): 54-64