A 45-year-old woman with no symptoms underwent upper gastrointestinal endoscopy. A discolored area was noted at the greater curvature of the gastric upper body. Endoscopic ultrasonography demonstrated thickening of the second sonographic layer indicating that the depth of invasion was confined to the mucosa. A urea breath test and anti-Helicobacter pylori antibody test were negative. A computed tomography scan showed a consolidation at the right lung. Gastric biopsy and transbronchial lung biopsy (TBLB) demonstrated a monotonous proliferation of atypical small lymphocytes. A diagnosis of gastric marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) was made. The clinical stage was stage IV. A genetic analysis showed rearrangement of the joining region of the immunoglobulin heavy chain gene and identical clones in both lesions. An API2-MALT1 fusion gene was detected in the gastric lesion. After H. pylori eradication treatment, combination treatment with rituximab plus CHOP (R-CHOP) was performed; 6 months later an endoscopy revealed complete disappearance of the lesion. Multiple gastric biopsies showed no infiltrating atypical lymphocytes. Similarly, the lesion in the lung showed complete remission (CR) on CT and TBLB. This report shows that a gastric MALT lymphoma located in the mucosa and disseminated to the lung maintained CR by R-CHOP.

To assess the clinical and endoscopic presentation of primary gastric lymphoma.

Remission rate and long-term survival in patients with gastric lymphoma mainly depend on disease stage at diagnosis. Series reporting clinical and endoscopic presentation of gastric lymphoma are generally small and heterogeneous.

Systematic review with pooled-data analysis assessing clinical and endoscopic presentation of primary gastric lymphoma.

Data regarding 2000 patients were collected. Overall, males were slightly more prevalent, alarm symptoms were absent in near half of the patients, lymphoma was diagnosed in a stage >I in one-third of the patients, and Helicobacter pylori infection was present in 88.8% of considered patients. At endoscopy, the ulcerative type was the most frequent presentation, although low-grade lymphoma was diagnosed on normal/hyperemic gastric mucosa in 9% of cases. Patients with high-grade lymphoma presented alarm symptoms (anemia and/or melena and/or hemorrhage, persistent vomiting, weight loss), an exophytic or ulcerative lesion, a stage III-IV, and a H. pylori negative status more frequently than low-grade lymphoma cases.

Our pooled-data analysis showed that gastric lymphoma is still disappointingly diagnosed in an advanced stage in a large number of patients. This is probably due to presence of nonspecific symptoms at initial clinical presentation and/or a normal appearing mucosa at endoscopic observation in the early stages.

Gastric mucosa associated lymphoid tissue (MALT) lymphoma has recently been incorporated into the World Health Organization (WHO) lymphoma classification, termed as extranodal marginal zone B-cell lymphoma of MALT-type. In about 90% of cases this lymphoma is associated with H pylori infection which has been clearly shown to play a causative role in lymphomagenesis. Although much knowledge has been gained in defining the clinical features, natural history, pathology, and molecular genetics of the disease in the last decade, the optimal treatment approach for gastric MALT lymphomas, especially locally advanced cases, is still evolving. In this review we focus on data for the therapeutic, stage dependent management of gastric MALT lymphoma. Hence, the role of eradication therapy, surgery, chemotherapy and radiotherapy is critically analyzed. Based on these data, we suggest a therapeutic algorithm that might help to better stratify patients for optimal treatment success.

Association of gastric mucosa-associated lymphoid tissue (MALT) low-grade lymphoma and adenocarcinoma has repeatedly been reported. The aim of this study was to evaluate the frequency and the spreading of atrophy and intestinal metaplasia in gastric mucosa of patients with gastric MALT lymphoma followed after conservative treatment.

Forty-five patients (mean age 45 +/- 2.1 yr) with gastric MALT lymphoma, treated by Helicobacter pylori eradication, chemotherapy with per os single alkylating agents, or both treatments have been followed by gastroscopy with biopsies in antrum and corpus at least once a year. Univariate and multivariate analysis evaluated the association between the appearance of atrophy and intestinal metaplasia in antrum or corpus and different factors related to patients, H. pylori status, lymphoma features, and treatment. In addition, histological aspects of gastric biopsies at the diagnosis period and at the end of follow-up were compared with those of two control groups of age-matched patients with H. pylori gastritis.

At the diagnosis time, only intestinal metaplasia in corpus was more frequent in patients with gastric MALT lymphoma than in patients with nonulcer dyspepsia. Within median follow-up of 54.4 months (range 9-196), the percentage of patients with gastric atrophy and intestinal metaplasia increased significantly and became significantly higher than in age-matched nonulcer dyspepsia patients. Multivariate analysis showed significant association between corpus intestinal metaplasia and corpus atrophy, intestinal metaplasia in antrum, and duration of the follow-up.

Conservative management of gastric MALT lymphoma including H. pylori eradication is associated with progression of gastric atrophy and intestinal metaplasia with frequent involvement of the corpus which is known to be a precancerous condition. These findings show that long-term endoscopic monitoring should be recommended in such patients.

Although the stomach is the most frequent site of intestinal lymphomas, few data are available on both clinical endoscopic presentation of gastric lymphoma and possible differences between low-grade and high-grade lymphomas.

Clinical, histological and endoscopic records of consecutive patients with primary low-grade or high-grade lymphoma diagnosed were retrieved. Symptoms were categorized as 'alarm' or 'not alarm'. The endoscopic findings were classified as 'normal' or 'abnormal'.

Overall, 144 patients with primary gastric lymphoma were detected, including 74 low-grade and 70 high-grade lymphoma. Alarm symptoms, particularly persistent vomiting and weight loss, were more frequently present in patients with high-grade lymphoma than in those with low-grade lymphoma (54% vs. 28%; P = 0.002). Low-grade lymphomas presented as 'normal' appearing mucosa (20% vs. 0%; P = 0.0004) or petechial haemorrhage in the fundus (9% vs. 0%; P = 0.02) more frequently than high-grade lymphomas, being also more often confined to the antrum (47% vs. 27%, P = 0.03) and associated with Helicobacter pylori infection (88% vs. 52%, P < 0.0001). On the contrary, high-grade lymphomas presented more commonly as ulcerative type (70% vs. 52%; P = 0.03), being also more frequently diagnosed in stage >I when compared with low-grade lymphomas (70% vs. 21%, P < 0.0001).

The overall prevalence of alarm symptoms is quite low and may be absent in more than 70% of patients with low-grade lymphoma.

A 76-year-old woman was admitted for evaluation of esophagitis complicating limited cutaneous systemic sclerosis. Endoscopy showed persistent grade III esophagitis and an erythematous antral lesion found upon biopsy to be a lymphoma of mucosa-associated lymphoid tissue (MALT). Tests were positive for Helicobacter pylori. Moderate mucosal infiltration by endoscopic ultrasonography was the only finding from staging investigations. Six months after treatment to eradicate H. pylori, a repeat endoscopy showed no evidence of the lesion.

MALT lymphomas are usually confined to the gastric wall. Gastric MALT lymphomas have a well-established association with H. pylori infection. The clinical manifestations are nonspecific. Endoscopy usually shows a focus of erythema or, less often, erosion. The diagnosis rests on histological examination of a biopsy, which shows infiltration by monoclonal cells whose immunophenotype is characteristic of marginal-zone B cells. Eradication of H. pylori is the mainstay of treatment.

The goals of the current study were to elucidate the long-term outcome of Helicobacter pylori eradication therapy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to clarify the therapeutic efficacy of stomach-conserving treatments for patients not responding to eradication therapy.

Ninety-six patients with gastric MALT lymphoma, including 17 patients with areas of diffuse large B-cell lymphoma, were treated by H. pylori eradication. Patients not responding to eradication therapy underwent either a gastrectomy, multiagent chemotherapy, oral monochemotherapy (OMC), or radiotherapy (RT). Predictive factors for the response to eradication therapy, overall survival (OS), and event-free survival (EFS) were determined by the Kaplan-Meier analysis with the log-rank test. The efficacy of second-line treatment was compared between OMC and RT.

After eradication therapy, 62 (65%) patients achieved complete disease remission (CR). Transient histologic disease recurrence was confirmed in 4 (6.5%) of 62 patients with CR during the follow-up (median, 37.5 months). The OS and EFS probabilities after 5 years were 0.96 and 0.80, respectively. Second-line treatment was performed in 31 patients; gastrectomy in 4 patients, multiagent chemotherapy in 5 patients, OMC in 12 patients, and RT in 10 patients. There were no differences in the CR rate, OS, EFS, or toxicity between the OMC and RT groups.

H. pylori eradication therapy was an effective first-line treatment for patients with gastric MALT lymphoma, which led to a favorable long-term outcome. OMC and RT had an equivalent efficacy as a second-line treatment in nonresponding patients to eradication therapy.

To determine the impact of translocation t(11;18) on response to oral alkylating agents in gastric mucosa-associated lymphoid tissue lymphoma (GML).

Fifty-three patients with a GML were studied. Helicobacter pylori-positive patients (n = 34) received anti-H pylori treatment and H pylori-negative patients (n = 19) or patients who failed to respond to anti-H pylori treatment received oral alkylating agents. t(11;18) was detected by reverse transcription polymerase chain reaction from frozen gastric biopsies.

t(11;18) was detected in 32% of patients. It was more prevalent in H pylori-negative as compared with H pylori-positive patients (12 of 19 v five of 34 patients; P = .0005). Among 31 H pylori-eradicated patients, t(11;18) was detected in three patients, all of whom experienced treatment failure, and it was absent in 28 patients: 21 patients (75%) were in remission and seven patients (25%) experienced treatment failure (P = .03). Among 21 patients who received an alkylating agent, t(11;18) was detected in 12 patients: five patients (42%) were in remission and seven patients (58%) experienced treatment failure. t(11;18) was absent in nine patients: eight patients (89%) were in remission and one patient (11%) experienced treatment failure by the end of treatment. Four patients in remission relapsed during follow-up (median, 7 years): they all had t(11;18). Durable remission was obtained in eight (89%) of the nine patients without t(11;18) versus one of the 12 patients (8%) with t(11;18) (P = .0003).

Presence of t(11;18) in GML is predictive of resistance to oral alkylating agents, with less than 10% of durable remission at long-term follow-up.

Primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue may regress with conservative treatment such as anti-Helicobacterpylori therapy or monochemotherapy. The aims of the present study were to analyze the predictive factors of response to anti-H. pylori treatment, to assess the effects of an adjuvant therapy in responding patients, and to evaluate an alternative therapy in nonresponding patients.

From 1995 to 2000, 48 H. pylori-infected patients with localized primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue were treated with anti-H. pylori therapy. Endoscopic and endoscopic ultrasonography features and histological grading of large cells' proportion were analyzed. Eradication of H. pylori and tumoral response were assessed at 2 and 6 months, respectively. From 1996, patients in remission at 6 months were randomized to receive either chlorambucil p.o. for 6 months or no treatment. Patients who did not respond to H. pylori eradication received chlorambucil p.o. for 1 yr.

Among the 48 treated patients, 33 (69%) were in complete (n = 28) or in partial (n = 5) remission, and 15 (31%) were in treatment failure at 6 months. H. pylori was eradicated in 47 patients. The response was not correlated with the endoscopic features or with the histological grade. In contrast, it was related to ultrasonographic features: remission was achieved in 76% of patients when no perigastric lymph node was detected versus only 33% when endoscopic ultrasonography showed presence of lymph nodes (p = 0.025). All responding patients remained in remission (median 34 months) whatever the treatment they received (no treatment or chlorambucil). Remission could be achieved with chlorambucil in 58% of the nonresponding patients to anti-H. pylori treatment.

The major negative predictive factor of the tumoral response to anti-H. pylori treatment in patients with primary gastric low-grade B-cell lymphoma of mucosaassociated lymphoid tissue was the presence of perigastric lymph nodes on endoscopic ultrasonography. In responding patients, remission remained stable, suggesting that adjuvant chemotherapy was not useful. In patients who failed to respond to H. pylori eradication, monochemotherapy with chlorambucil proved to be efficient, but new therapeutic modalities should be evaluated to improve the control of the tumoral process.

While a close association between gastric mucosa associated lymphoid tissue (MALT) lymphoma and Helicobacter pylori infection has been established, there are still cases which do not respond to H pylori eradication.

To investigate the clinicopathological factors which may help predict the therapeutic efficacy of H pylori eradication in gastric MALT lymphoma.

Forty one patients with gastric MALT lymphoma, including low and high grade lesions.

After endosonographic staging was determined, H pylori was eradicated in all patients, and the subsequent gastric pathological course was then investigated.

Complete regression of MALT lymphoma was observed in 29(71%) patients, partial regression in five (12%), and no regression in seven (17%). Twenty six (93%) of 28 MALT lymphomas restricted to the mucosa but only three (23%) of 13 lymphomas which invaded the deep portion of the submucosa or beyond completely regressed. Kaplan-Meier analysis for the probability of complete regression of MALT lymphoma revealed a significant difference between tumours restricted to the mucosa and those invading the submucosa deeply or beyond (p<0.05). Neither the presence of a high grade component, perigastric lymphadenopathy, nor clinical staging prior to eradication correlated with the probability of lymphoma regression.

Assessment of deep submucosal invasion by endosonography is valuable for predicting the efficacy of H pylori eradication in gastric MALT lymphoma.

It was recently reported that low-grade gastric lymphoma of mucosa-associated lymphoid tissue (MALT) was regressed by the eradication of Helicobacter pylori. The aim of this study was to confirm the effect of H. pylori eradication on low-grade gastric MALT lymphoma and to investigate the whitish mucosa that appeared with regression of the lesions.

Forty-seven H. pylori-positive patients with low-grade gastric MALT lymphoma were treated by using triple therapy. Biopsy specimens were histologically graded and B cell clonality was examined by using reverse transcription-polymerase chain reaction before and after eradication treatment. The relationship between the appearance of whitish mucosa and the degree of gastric gland loss was evaluated.

Histologic regression was observed 2 months after eradication therapy in 42 of 47 patients. However, B cell monoclonality changed to polyclonality in only 23 patients during the follow-up period. The appearance of whitish mucosa in patients who showed histologic regression became more frequent as the degree of gastric gland loss increased (P< 0.001).

Most low-grade gastric MALT lymphoma histologically regressed after H. pylori eradication. The appearance of whitish mucosa after histologic regression reflected the degree of gastric gland loss. Whitish mucosa is an endoscopic characteristic and may be an endoscopic marker for regression of low-grade gastric MALT lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT) B cell lymphomas contain activated helper T cells. The evidence supports the presence of mechanisms of T cell dependence underlying the development of these lymphomas. It appears that the T cells, which activate B cells, may contribute to lymphoma pathogenesis. Co-stimulatory molecules necessary for effective B cell/T cell interaction are expressed in MALT lymphomas. The studies suggest that CD40 signaling, in combination with cytokines, is essential for the development and progression of MALT lymphomas. Activated T cells of low grade gastric MALT lymphoma, while delivering full help to B cells, are apparently deficient in two cytotoxic mechanisms involved in the concomitant control of B cell growth.

Small cell mucosa-associated lymphoid tissue (MALT) lymphomas rarely affect the duodenum, and optimal treatment has not been defined. The aim of this case series was to determine the clinical features and outcome of duodenal MALT lymphoma in four patients (three men, one woman; median age 52 yr) treated with cyclophosphamide p.o. Initial manifestations were abdominal pain (n = 4), vomiting (n = 2), and an obstructive syndrome (n = 1). MALT lymphoma was diagnosed on the basis of endoscopic biopsies. It was localized in the duodenum in three cases and involved the entire small bowel in one case. Tumor infiltration was limited to the duodenal wall in one case and was associated with locoregional lymphadenopathy in three cases. The patients were graded EI (n = 1) and EII1 (n = 3), respectively, according to the Ann Arbor classification revised by Musshof. Cyclophosphamide, 100 mg daily, was administered p.o. for 18 months. Gastroscopy with biopsies, radiography of the small intestine and abdominal CT (CT) were performed every 6 months. Complete remission was defined by morphological and histological normalization, and partial remission as morphological normalization only. Follow-up lasted from 9 to 65 months. Three patients were in complete remission at 18 months: two relapsed after 2 yr and one was still in complete remission at 65 months. The patient with 9 months of follow-up was in complete remission at 6 months. The two patients who relapsed did not complain of symptoms, and no morphological abnormalities were seen. Relapse was diagnosed on histological grounds. Cyclophosphamide monotherapy p.o. thus seems well adapted to this slowly progressive disease, but it is unclear whether it should be resumed in the case of histological relapse or only in the case of symptomatic relapse. (Am J Gastroenterol 2000;95:536-539. (O 2000 by Am. Coll. of Gastroenterology)

To describe upper gastrointestinal (Gl) examination findings of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to correlate them with pathologic examination findings.

A retrospective review of upper Gl examinations was performed in 25 patients with proved low-grade gastric MALT lymphomas. Upper Gl examinations were reviewed for common findings and most probable diagnosis, and these findings were correlated with pathologic findings in resected specimens in 15 patients.

The common findings at upper Gl examination included mucosal nodularity (n = 13), ulcer (n = 12), rugal thickening (n = 6), mass (n = 4), and enlarged areae gastricae (n = 2). The most probable diagnoses were early gastric carcinoma (n = 7), advanced gastric carcinoma (n = 6), gastritis (n = 9), and lymphoma (n = 3). Of 17 lesions found on resected specimens, six ulcers and two masses were not depicted at barium study. Disorganized convergent rugae projecting to multiple points and vague ulcer margins were present in four and seven lesions, respectively. Multiple ulcers were seen in two patients.

Although the common radiographic and pathologic findings observed in low-grade gastric MALT lymphomas were similar to those of gastric carcinomas or gastritis, disorganized convergent rugae, vague ulcer margins, and multiplicity of lesions may be helpful in differentiating them from gastric carcinomas or gastritis.

We report herein the case of a patient found to have mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum forming multiple polypoid lesions. Endoscopic examination revealed multiple small nodules with a yellow-white, rough surface in the duodenal bulb. Histopathological and immunological findings subsequently suggested low-grade B-cell MALT lymphoma. Cytologically, MALT lymphoma is similar to multiple lymphomatous polyposis (MLP); however, this case, which involved multiple polypoid lesions, was confirmed not to be MLP.

Although antibiotic therapy is emerging as effective initial treatment for patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT), there is a subset of patients for whom antibiotics are ineffective or inappropriate. Surgical resection can be curative, but total gastrectomy may be required for the eradication of all disease. To identify the optimal nonantibiotic therapy for early stage gastric MALT lymphoma, the authors retrospectively evaluated the Massachusetts General Hospital experience with gastric MALT lymphoma.

Disease patterns and treatment outcomes were retrospectively analyzed in data from 21 consecutive patients with gastric MALT lymphoma who were treated between 1978 and 1995 at the Massachusetts General Hospital.

Sixteen patients were Stage IE, and 5 were in higher stages. Treatment consisted of resection with or without radiation or chemotherapy (14 patients), radiation alone (4 patients), or radiation plus chemotherapy (2 patients). Thirteen Stage IE patients received local therapy only. The 10-year actuarial relapse free survival rate for Stage IE patients was 93%, with 1 relapse among 15 treated patients. Because the patient who relapsed was treated successfully with chemotherapy, the 10-year cancer free survival was 100%. Overall survival for Stage IE patients was 93% at 5 years and 58% at 10 years, with no deaths from lymphoma.

These data indicate that a high probability of long term remission can be achieved with only local treatment of patients with Stage I gastric MALT lymphoma. Preliminary results suggest that radiation therapy is well tolerated and effective and may well be the optimal nonantibiotic treatment for patients with localized gastric MALT lymphoma.

Gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma is a unique disease. A vast majority of lymphoma cells are centrocyte-like cells or resemble monocytoid B cells, and occasionally show plasmacytic differentiation. Immunophenotypical and immunogenotypical examinations have indicated that they are in the differentiation stage of memory B cells, whose normal counterparts are marginal zone lymphocytes or monocytoid B cells in the lymphoid tissues. It arises from chronic gastritis closely associated with Helicobacter pylori (H. pylori) infection. Mucosa-associated lymphoid tissue lymphomas of other organs are also based on acquired MALT associated with chronic inflammation or autoimmune diseases. Interestingly, the majority of gastric low-grade MALT lymphomas regress by the eradication of H. pylori. The lymphoma cells, however, are not derived from B cells reacting with H. pylori itself but from autoreactive B cells. Although the mechanism of their oncogenesis has not been clarified, previous data suggest that autoreactive B cells proliferate in response to H. pylori-specific T cells, presumably with some cytokines. The genetic instability of such B cells then induces chromosomal abnormalities including trisomy 3 and/or other genetic changes. These B cells have the ability of autonomic proliferation and, even so, they might be sensitive to T cell stimuli. Low-grade gastric lymphomas occasionally progress to high-grade malignancy. The high-grade component of MALT lymphomas are composed of large-sized lymphoma cells that are morphologically indistinguishable from nodal large B cell lymphomas. This high-grade transformation is associated with p53 abnormalities or Bcl-6 overexpression. Gastric MALT lymphoma may provide a useful model in understanding multistep lymphomagenesis.

Endoscopic ultrasonography is an appropriate procedure to assess the depth of tumoral infiltration in primary gastric lymphoma. The aims of the present study were to characterize the endoscopic ultrasonographic aspects of low-grade gastric lymphoma of mucosa-associated lymphoid tissue and to determine the value of this procedure in medical treatment assessment.

Between 1991 and 1996, 15 patients with low-grade gastric lymphoma of mucosa-associated lymphoid tissue were treated with oral cyclophosphamide and/or anti-Helicobacter pylori treatment. Endoscopic ultrasonography was carried out at the time of the diagnosis in all patients, 8 of whom (4 in complete remission and 4 with a stable or progressive disease) had at least one endoscopic ultrasonography examination within the treatment period (median follow-up 17 months).

The initial procedure showed an increased gastric wall thickness from 6 to 12 mm in 8 patients, equal to 5 mm in 5 patients, and normal in 2 patients. The thickening was predominantly of the mucosa alone and/or the submucosa but never extended beyond the muscularis propria. No lymph node was found. Gastric wall thickness returned to normal in the 4 patients in complete remission and remained thick in 3 of the 4 patients with a stable or progressive disease. Of these 3 patients, at least one set of biopsy samples, carried out during follow-up, showed the absence of lymphoma, but histology performed subsequently found evidence of disease.

Endoscopic ultrasonography differentiates superficial from infiltrative types of gastric lymphoma of mucosa-associated lymphoid tissue, which may have a prognostic significance and confirms remission or persistence of the disease with medical treatment during follow-up. When the gastric wall remains thick, even if histology is negative, repeated biopsies should be performed to detect evolving disease or relapse.

The aim of this study was to evaluate retrospectively the different treatment approaches and outcome of patients with stage IE and IIE gastric non-Hodgkin's lymphoma in a cancer registry. Between 1982 and 1992, the Comprehensive Cancer Centre South (CCCS), Eastern Section, The Netherlands, registered, in a population of 1 million people, a total of 81 cases of gastric lymphoma stage IE and IIE (43 men and 38 women). Median age was 69.7 years (range 30.4-88.1). According to the Working Formulation, the malignancy grade was: 9 low, 55 intermediate and 14 high. According to the MALT classification, the malignancy grade was: 38 low and 40 high. Grade was unknown in 3 patients. Patients received the following treatment modalities: surgery alone (n = 22), locoregional radiotherapy without (n = 12) or with (n = 13) surgery; or systemic chemotherapy alone (n = 10) or with radiotherapy and/or surgery (n = 18). No treatment was given or recorded in 6 patients. For stage IE, 5-year actuarial survival and relapse-free survival rates were, respectively, 76 and 64% in 18 patients who received only surgery; 70 and 67% in 17 patients given locoregional treatment (radiotherapy with or without surgery), and 76 and 62% in 13 patients given systemic treatment (chemotherapy alone or with radiotherapy and/or surgery). Radiotherapy as sole treatment seemed to be as effective as other treatment modalities in achieving local and abdominal control. For stage IIE, none of the 4 patients who were treated with surgery alone survived 5 years. The 5-year actuarial survival and relapse-free survival rates of 8 patients who received radiotherapy with or without surgery were, respectively, 25 and 17% and 49 and 33%, for 14 patients given systemic therapy (chemotherapy alone and/or radiotherapy/surgery). In stage IIE, local, abdominal as well as distant relapse were more common, irrespective of treatment modality. In the multivariate analyses, stage (P = 0.002), grade (P = 0.02), age (P = 0.04) and gender (P = 0.04) were significant prognostic factors. This report on a limited number of patients shows that the outcome of patients with stage IIE gastric lymphoma is much worse than for patients with stage IE. Grade, age, gender and particularly stage are much stronger indicators for survival than different modes of treatment. Systemic therapy might improve outcome for stage IIE, but not for stage IE, for which radiotherapy alone seems a good option.

To determine whether primary B-cell gastric lymphoma (GL) is one entity, we examined the expression of three adhesion molecules in the microvasculature of lymphomas. Stromal cells, including vascular endothelial cells, within lymphoid follicies of the gastric mucosa were also investigated. Twenty-two surgical specimens of GL were classified into low-grade malignant lymphoma arising from mucosa-associated lymphoid tissue (low-grade lymphoma, n = 9), and high-grade malignant lymphoma with (secondary high-grade lymphoma, n = 6) or without (primary high-grade lymphoma, n = 7) a low-grade component. The proportion of venules positive for ELAM-1 or VCAM-1 was significantly higher (P < 0.001) in primary high-grade lymphoma than in low-grade and secondary high-grade lymphomas. In gastric lymphoid follicles, the stromal cells of the germinal centre (GC) were positive for ICAM-1, ELAM-1, and VCAM-1, but the stromal cells of the marginal zone (MZ) were positive only for ICAM-1. We found two patterns of adhesion molecule expression in gastric lymphoid follicles, the MZ pattern and the GC pattern. Low-grade and secondary high-grade lymphomas, which had the MZ pattern, might be of MZ-cell lineage, but most primary high-grade lymphomas, which had the GC pattern, might be of follicular centre cell lineage.

Previous studies have shown that tumour cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue (MALT) type proliferate in vitro in response to heat-killed whole cell preparations of Helicobacter pylori, but only in the presence of tumour-infiltrating T cells. This response is strain-specific in that the tumours studied responded optimally to different strains of H. pylori. It was unclear from these studies, however, whether the ability to recognize the specific stimulating strains of H. pylori was a property of the tumour cells or the tumour-infiltrating T cells. This study shows that whereas the tumour cells do not respond to H. pylori, both freshly isolated tumour-infiltrating T cells and a T cell line derived from these cells proliferate in response to stimulating strains of H. pylori. T cells from the spleen of one of the patients do not share this property. These results suggest that B-cell proliferation in cases of low-grade gastric lymphoma of MALT type in vitro in response to H. pylori is due to recognition of H. pylori by tumour-infiltrating T cells, which in turn provide help for tumour cell proliferation. The observations provide an explanation for properties of gastric MALT-type lymphoma, such as regression following eradication of H. pylori and the tendency of the tumour to remain localized to the primary site.

The gastrointestinal tract is a common primary extranodal site for non-Hodgkin's lymphoma. There is however no uniform consensus on its pathological classification, clinical staging system and management. This paper reports the experience in the management of 425 Chinese patients with primary gastrointestinal lymphoma in Hong Kong from January 1975 to June 1993. There were 230 (54 per cent) males and 195 (46 per cent) females. Their median age was 53 years. The primary sites were: the esophagus in three (1 per cent), stomach in 238 (56 per cent), small intestine in 131 (31 per cent) and large intestine in 53 (12 per cent). According to the Working Formulation, there were 20 (4.7 per cent) small lymphocytic, 10 (2.4 per cent) follicular small cleaved cell, 15 (3.5 per cent) follicular mixed, five (1.2 per cent) follicular large cell, 40 (9.4 per cent) diffuse small cleaved cell, 50 (12 per cent) diffuse mixed, 181 (43 per cent) diffuse large cell, 30 (7.1 per cent) immunoblastic, five (1.2 per cent) lymphoblastic, 10 (2.4 per cent) diffuse small non-cleaved cell and 50 (14 per cent) unclassifiable lymphoma. Immunophenotyping was performed in 199 (47 per cent) patients: 90 per cent B-cell, 7 per cent T-cell and 3 per cent uncertain. According to a Manchester system, 81 (19 per cent) patients had stage I disease, 44 (10 per cent) stage II, 85 (20 per cent) stage III and 215 (51 per cent) stage IV. B symptoms were present in 275 (65 per cent) patients and bulky disease in 104 (25 per cent). Surgery followed by chemotherapy was the mainstay of treatment. Of the 408 patients treated, 63 per cent had a complete remission with relapse rate of 42 per cent. For those with complete remission, 47 per cent were free from disease at 5 years. The overall median survival of all patients was 45 per cent at 5 years. Multivariate analysis revealed that significant independent prognostic factors predicting better survival were young age of < 60 years, low grade histology, stage I and II disease and absence of bulky tumour. For gastric lymphoma, aggressive surgery did not significantly improve their outcome. Chemotherapy appears to play an important role in the management of gastrointestinal lymphoma. Better classification of the primary gastrointestinal lymphoma and more refined stratification of the patients according to the prognostic variables may allow individualization of treatment. Prospective randomized studies are essential to define the relative roles of surgery, chemotherapy and radiotherapy.

This study assessed the presentation, treatment, and prognosis of primary gastric lymphoma in general hospital practice and its relation to infection with Helicobacter pylori. The number of patients that would on the current recommendations have been suitable for H pylori eradication therapy was also examined. All lymphomas were graded according to a standard classification of gut lymphoma into high and low grade disease. Forty five patients (mean age 65 years) were identified. The overall five year survival was 40% with a trend in favour of an improved prognosis for low grade and stage I disease. H pylori was present in 80%. Only one of 18 patients with a low grade mucosa associated lymphoid tissue tumour had mucosal disease alone, which responded to omeprazole and amoxycillin. All other patients had bulk disease. These patients were treated by surgery, chemotherapy or radiotherapy or a combination of these treatments. In district hospital practice, most cases of primary gastric lymphoma have bulk disease at presentation. Even in patients with low grade gastric lymphoma on histological examination, many on the current evidence would not be suitable for anti-H pylori therapy alone.

We report 11 cases of gastric lymphoma that harbor the Epstein-Barr virus (EBV) encoded small messenger RNA, EBER-1, detected by in situ hybridization. The cases represented 18% of 61 consecutive gastric lymphomas from three institutions in Hong Kong between 1988 and 1993. The mean age of patients was 62 years (range, 33 to 87). The male to female ratio was 5:6. Nine of the 11 (81.8%) EBER-1+ gastric lymphomas were diffuse large cell lymphomas of B-cell type without low grade components. Macroscopically these lymphomas appeared either as large noncleaved cell (centroblastic) or immunoblastic type. From the available follow-up data, five of the nine patients with B-cell lymphoma were alive and well 48, 40, 14, 13, and 12 months, respectively, after gastrectomy and chemotherapy. One patient died of postoperative pneumonia and one died of a second malignancy (esophageal squamous carcinoma) 40 months after gastrectomy. None of the EBER-1+ B-cell gastric lymphomas showed histological features characteristic of low grade lymphoma of the mucosa-associated lymphoid tissue (MALT) type reported to be common in some Western countries. Of the two patients with T-cell lymphoma, one had a pleomorphic T-cell lymphoma and the other had an angiocentric lymphoma. The former was lost to follow-up after the biopsy and the latter presented with gastric perforation and died 1.5 months after gastrectomy. It is concluded that a significant proportion of gastric lymphomas in Hong Kong Chinese are EBV-related and that they show histological features more akin to conventional node-based lymphomas than to MALT-type lymphomas.

The optimal management of primary gastrointestinal lymphoma including the use of surgery remains unsettled. This prospective study aimed to determine the prognostic factors of primary gastrointestinal lymphoma and to evaluate a therapeutic strategy based on surgical tumor reduction, followed by chemotherapy adapted to the histological type of tumor and tumor removal or nonremoval.

Ninety-one patients were included (mean age, 50.4 years) with mainly gastric (61%) or several digestive tract organ (18%) involved sites in clinical stages IE (43%), IIE (27%), and IV (30%). Three therapeutic groups were defined: group I, patients with low-grade lymphoma (n = 28); group II, patients with high-grade lymphoma who had complete tumor removal (n = 24); and group III, patients with high-grade lymphoma who had only partial or no tumor removal (n = 39). Each group underwent adapted chemotherapy.

The respective overall 5-year survival rates for groups I, II, and III were 81% +/- 6%, 100%, and 56% +/- 8%, respectively (P < 0.0001). By Cox multivariate analysis, the prognostic factors of survival were age under 65 (P < 0.05), gastric localization (P < 0.05), stage IE (P < 0.001), and radical or incomplete surgery (P < 0.01).

Combined radical surgery and chemotherapy according to histological grading is associated with prolonged remission in patients with primary digestive tract lymphoma. Moreover, compared with chemotherapy alone, incomplete resection of tumor is associated with increased survival of high-grade lymphomas.