Three cases of <i>H. pylori</i>-negative gastric MALT lymphoma successfully treated with radiation therapy
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Abstract:
Approximately 90% of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma are infected with H. pylori. The eradication of H. pylori leads to complete remission (CR) of the disease in 70-80% of the gastric MALT lymphoma with H. pylori infection. We reported three cases of H. pylori negative gastric MALT lymphoma that were confirmed as CR treating by radiation therapy (RT) . All cases confirmed H. pylori negative by 4 or 5 H. pylori tests. In addition, H. heilmannii was negative in all cases. CR was confirmed at the time of 1 or 2 years after RT. In conclusion, RT is useful for treating H. pylori negative gastric MALT lymphoma.Keywords:
Gastric lymphoma
Mucosa-associated lymphoid tissue
BACKGROUND
Most low grade gastric lymphomas arising from the mucosa associated lymphoid tissue (MALT) are related to Helicobacter pylori colonisation. Cases with disease limited to the stomach can be cured after H pylori eradication and remain in remission for years. In contrast, high grade lymphomas of the stomach, although also related toH pylori, do not usually respond to eradication treatment.CASE REPORT
A 36 year old patient was referred from another hospital with a diagnosis of a low grade gastric MALT lymphoma associated with H pylori. The patient was in stage I and while waiting for the biopsies to be reviewed H pylori eradication therapy was given as the first step of treatment. Review of the biopsies showed a high grade immunoblastic lymphoma with areas of low grade gastric MALT lymphoma (high grade gastric MALT lymphoma or diffuse large B cell lymphoma with areas of MALT type lymphoma of the WHO classification). The patient received no further treatment but has been closely followed up for 32 months with sequential endoscopies to obtain biopsies for histological studies, H pylori cultures, and polymerase chain reaction analysis of the IgH gene.RESULTS
AfterH pylori eradication the patient had a complete histological response that has been maintained for 32 months. Monoclonal IgH gene rearrangement persisted for 32 months.CONCLUSION
The response of this patient indicates the possibility that some cases of high grade gastric MALT lymphoma (possibly patients in stage I with a superficial or limited disease) may still be responsive toH pylori antigenic drive and may be cured with eradication therapy. Prospective studies should be performed to identify patients with high grade gastric MALT lymphomas that may respond to eradication therapy and be spared of other more aggressive treatments.Mucosa-associated lymphoid tissue
Gastric lymphoma
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The frequency of reported cases of primary gastric mucosa-associated lymphoid tissue (MALT)-lymphoma is increasing worldwide. Helicobacter pylori plays a preponderant role in its pathogenesis. Gastric MALT-lymphoma arises from nonrecirculating centrocytelike cells located at the periphery of reactive lymphoid follicles, which are common in patients infected with this microorganism. Histopathologic features other than lymphoid follicles have not been well described. In this study the authors describe the morphologic changes in the gastric mucosa adjacent to MALT-lymphomas. From the files of the departments of pathology at the Instituto Nacional de Cancerologia and the Instituto Nacional de la Nutricion in Mexico City, primary gastric MALT-lymphomas were retrieved. Patients with hematoxylin-eosin-stained histologic sections, including the overt neoplasia and the neighboring gastric mucosa, were selected. Lymphoid follicles as well as intestinal metaplasia, atrophy, and eosinophils were evaluated as present or absent and graded as proposed by the Updated Sydney System for gastritis. Fifty-one patients were eligible for analysis. There were 35 low-grade and 16 high-grade primary MALT-lymphomas. Forty-seven patients (92.6%) showed reactive lymphoid follicles in the neighboring mucosa, 32 patients (69.5%) had intestinal metaplasia, and 26 patients (54.1%) demonstrated atrophy. In 41 patients (73.8%) there was an increased number of eosinophils. Our findings suggest that lymphoid follicles, intestinal metaplasia, atrophy, and eosinophils in an endoscopic biopsy are markers of both gastric lymphoma and carcinoma.
Intestinal metaplasia
Mucosa-associated lymphoid tissue
Gastric lymphoma
Metaplasia
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Gastric lymphoma
Mucosa-associated lymphoid tissue
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Abstract Background and Aims: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa‐associated lymphoid tissue (MALT) lymphoma and diffuse large B‐cell lymphoma without a MALT lymphoma component (DLL). Methods: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low‐grade MALT lymphoma, 10 patients with high‐grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age‐ and sex‐matched control subjects. Results: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low‐grade MALT lymphomas and 1/9 for high‐grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly ( P < 0.05). Ninety‐two percent of low‐grade MALT lymphomas and 80% of high‐grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low‐grade MALT lymphoma than in age‐ and sex‐matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls. Conclusions: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis.
Mucosa-associated lymphoid tissue
Gastric lymphoma
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Mucosa-associated lymphoid tissue (MALT) is found in the surface epithelium of the stomach. MALT lymphoma is extranodal lymphoma originating from MALT. In the stomach, a strong association with Helicobacter pylori infection has been demonstrated. Low-grade gastric MALT lymphoma has been reported to have variable features at upper gastrointestinal (UGI) examination. Twenty-two patients with low-grade MALT lymphoma had ulcers (n = 11), fold thickening (n = 7), mucosal nodularity (n = 7), masses (n = 6), or prominent areae gastricae (n = 4) at UGI examination. Six patients with high-grade MALT lymphoma had masses (n = 4), fold thickening (n = 3), ulcers (n = 1), or mucosal nodularity (n = 1) at UGI examination. These findings were similar to those in gastric carcinoma or gastritis. Differentiation of low-grade MALT lymphoma from gastritis or gastric carcinoma was more difficult than differentiation of high-grade MALT lymphoma. Lesions of MALT lymphoma associated with H pylori gastritis were diffuse or multiple in 65% of cases; however, lesions of MALT lymphoma without proved H pylori gastritis were focal or solitary in 80% of cases. Therefore, multiplicity of lesions in MALT lymphoma was closely associated with H pylori infection.
Mucosa-associated lymphoid tissue
Gastric lymphoma
Chronic gastritis
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Mucosa-associated lymphoid tissue
Gastric lymphoma
Hematology
Immunoglobulin heavy chain
BCL10
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Primary gastric lymphoma is the most common extranodal site of non-Hodgkin lymphoma [1] and represents 3–5% of gastric neoplastic lesions [2]. The most frequent histologic subtypes are extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type and diffuse large B-cell lymphoma (DLBCL) [3]. The incidence of developing primary gastric lymphoma is 2–3 times higher in men than in women [4]. The incidence of MALT lymphoma increased significantly in patients over 40 years of age in a retrospective study [5]. Even if gastric MALT lymphomas are low-grade lesions and localized [6], they can rarely be transformed into high-grade diffuse large B-cell lymphomas [7, 8]. Herein, the etiology, risk factors, diagnosis, treatment, and prognosis of gastric MALT lymphomas are summarized.
Mucosa-associated lymphoid tissue
Gastric lymphoma
Etiology
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CagA
Gastric lymphoma
Mucosa-associated lymphoid tissue
Spirillaceae
Atrophic gastritis
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The most common primary site of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the gastrointestinal tract, particularly the stomach. The relationship of MALT lymphomas, however, with the more commonly occurring large B-cell gastric lymphoma has not been directly discussed except in the report of Chan et al. (1990), which lacked clinical information regarding the behavior of these tumors. To elucidate the relationship between high-grade large-cell lymphoma and MALT lymphoma, we studied in detail the histopathological and clinicopathologic features with the survival date of 77 Japanese cases of primary gastric lymphoma (PGL) of B-cell type. Based on degree of morphologically recognizable low- or high-grade components of the tumor, PGL was divided into four types: 18 cases of pure MALT lymphoma (type I); 13 cases of MALT lymphoma with small area of high-grade lymphoma (type II); 22 cases of high-grade lymphoma with small areas of MALT lymphoma (type III); and 24 cases pure high-grade lymphoma (type IV). Corresponding to the differences in the histologic pictures of each type, there were differences in the gross appearance, pathologic stage (including depth of invasion) and prognosis. These data suggests that both MALT and high-grade lymphomas of the stomach belong to the same cell lineage and constitute a pathological spectrum and that the histological grouping of PGL is clinico-pathologically useful.
Gastric lymphoma
Mucosa-associated lymphoid tissue
B-cell lymphoma
Large cell
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Histologic features of low-grade gastric lymphomas of mucosa-associated lymphoid tissue (MALT) have been extensively described, and transformation to a large cell (high-grade) lymphoma can occur. We characterize high-grade gastric lymphoma histologically in an attempt to distinguish between MALT-type and non-MALT-type lesions. We studied a series of 60 gastric lymphomas and characterized them clinically, histopathologically, and immunophenotypically. Low-grade gastric lymphomas were classified according to established criteria. High-grade lymphomas were classified in three groups based on the presence or absence of a low-grade component and lymphoepithelial lesions (LELs): 1) high-grade MALT lymphomas appearing in low-grade MALT lymphomas (LG/HG MALT lymphoma); 2) large cell lymphoma with LELs composed of large cells (high-grade LELs) but without a low-grade component (HG MALT lymphoma); and 3) diffuse large cell lymphoma without a low-grade MALT lymphoma component or LELs (DLCL). Twenty-two lymphomas were classified as low-grade MALT lymphomas, 16 as LG/HG MALT lymphomas, 10 as HG MALT lymphomas, and 12 as DLCL. B-cell immunophenotype was confirmed in all 55 cases in which immunophenotyping was performed. Low-grade LELs were seen in all low-grade MALT lymphomas, and CD20(L26) expression confirmed B-cell phenotype in the LELs in 20 of 20 cases. Clinical follow-up was available for 56 patients (range, 1-264 months; mean, 57 months). Actuarial analysis of disease-specific survival and relapse-free survival showed that clinical stage was highly statistically significant (P < 0.0001), whereas histologic type and grade approached statistical significance. Multivariate analysis showed that clinical stage was the only significant factor in relapse-free and disease-specific survival.
Mucosa-associated lymphoid tissue
Immunophenotyping
Gastric lymphoma
Large cell
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