High-grade Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

Is the routine histopathological analysis of all gallbladders justified?

66,000 cholecystectomies are performed annually in the UK. Nationwide, all gallbladders are routinely sent for histological analysis to exclude incidental malignancy. This comes at significant cost to an overstretched National Health Service. This study set out to assess the utility of routine histopathological analysis following cholecystectomy. We performed a large, single-centre, retrospective analysis of all gallbladder specimens examined between February 2013 and December 2016 at our district general hospital. Specimens obtained in elective and emergency cases, through laparoscopic or open surgery, were included. A total of 752 gallbladder specimens were analysed. The mean age at the time of resection was 51 years, and the female:male ratio was 2.8:1. Seven (0.93%) specimens were reported to show suspicious histopathological features; epithelial atypia (1), low-grade epithelial dysplasia (2), high-grade epithelial dysplasia (1), papillary adenoma (1), MALT lymphoma (1) and invasive adenocarcinoma (1). In all seven cases, there was no clinical suspicion of gallbladder malignancy prior to surgery or suspicious pre-operative ultrasound scan findings. Gross macroscopic changes were noted at the time of resection in three cases. Four patients required further investigation and subsequent follow-up. All specimens deemed to be suspicious derived from patients over 50 years of age at the time of resection. Pre-operative investigations and macroscopic appearance at cholecystectomy may be inadequate in identifying patients with clinically important pathology. Routine histological analysis allows early identification. However, further work will assess whether more selective requests may help achieve the balance between cost-saving and safety in the context of a resource-limited healthcare service.

Primary gastrointestinal lymphomas - A study of 81 Cases from a Tertiary Healthcare Centre.

Purpose: Retrospective analysis of 81 routinely diagnosed gastrointestinal (GI) lymphoma to illustrate clinicopathological and immunohistochemical characteristics with predisposing condition. Materials and Methods: Age, sex, site, tumour stage, associated pathological features like lympho-epithelial lesion (LEL), atrophic gastritis (AG), intestinal metaplasia (IM) and enteropathy changes were analysed. Requisite immunohistochemical panel was applied wherever needed. Results: There were 55 male and 26 female patients with median age of 54.5 years. Site wise distributions were stomach 40, small intestine 22, colon 4, cecum 2, ileocecum 3, esophagus 1 and multiple sites 9. Histological subtypes were mucosa associated lymphoid tissue lymphoma (MALTOMA) 48, diffuse large B cell lymphoma (DLBL) 21, T cell lymphoma 9 [5 anaplastic large cell lymphoma (ALCL) and 4 enteropathy associated T cell lymphoma (EATL)], immunoproliferative small intestinal disease (IPSID) 2 and follicular lymphoma 1. LEL was present in 31 cases. Of the 19 AG, 8 had associated IM, and 1 case each had associated H Pylori infection and neuroendocrine tumor. Enteropathy was observed in 4 EATL, and one case each of DLBL and high grade MALTOMA. Giardia infection was present in 1 low grade duodenal MALTOMA. Of the 24 resected specimens, 16 were stage IE, 7 stage IIE and 1 stage IV (Mushoff's staging). Conclusion: Primary GI lymphoma was frequently observed in 6 th decade of life with male preponderance. Stomach was the commonest site and high grade MALTOMA being the commonest histological variant. Isolated colonic involvement and intestinal perforations were not infrequent. Rare variants like ALCL and follicular lymphomas were also observed.

Tu1091 Gastrointestinal Stromal Tumors Show Strong Association With Synchronous or Metachronous Other Malignancies

Introduction: Primary GI lymphoma are a rare disease. Multicenter studies were, therefore, initiated in the 90ies with various published results in subgroups of GI lymphoma. We here report our long-term findings in patients with any primary GI lymphoma who were not treated within a controlled clinical trial. Method: As a German reference center patients with GI lymphoma are regulary presented to our institution. From 1993 on, we saw 102 consecutive patients (59 male and 43 female, age 31-89 years) with primary GI lymphoma: gastric MALT lymphoma = 76 (63 stage I, 6 stage II, 7 stage III/IV); secondary high grade MALT lymphoma = 3; diffuse large B-cell lymphoma (DLBCL) = 14 (Stage I/II/III-IV = 8/4/2); Burkitt lymphoma = 1; intestinal follicular lymphoma (FL) grade I/II = 8 (stage I/II/III-IV = 5/1/2). Treatment strategies were as follows:MALT-lymphoma: H. pylori eradication, radiation (RTx) and/or chemotherapy (CTx) in stages . II or in case of eradication failure; DLBCL: CTx except in 3 cases treated by H. pylori eradication only; FL: no therapy, CTx or RTx. Results: 26/47 patients (55%) with MALT lymphoma achieved complete remission (CR) after exclusive H. pylori eradication. Application of all therapeutic procedures resulted in CR = 53/76 (70%) and PR with watch-and-wait = 22/76 (29%). There was only 1 patient revealing progression. In DLBCL, 12 (86%) achieved CR after 1-3 line therapies. In FL, watch-and-wait resulted in long-term stable disease in n=5, CR after RTx in 1 case, and stable disease after CTx in 2 cases. Conclusion: Despite a negative selection of patients being presented to our reference center the overall treatment results in all subgroups of GI lymphoma are excellent when all treatment options are offered in a sequential therapy strategy. Watch-and-wait is a promising approach in MALT lymphoma with residual disease following H. pylori eradication and in FL.

Tu1090 19-Year Single Center Experience in the Management of Patients With Primary Gastrointestinal (GI) Lymphoma

Introduction: Primary GI lymphoma are a rare disease. Multicenter studies were, therefore, initiated in the 90ies with various published results in subgroups of GI lymphoma. We here report our long-term findings in patients with any primary GI lymphoma who were not treated within a controlled clinical trial. Method: As a German reference center patients with GI lymphoma are regulary presented to our institution. From 1993 on, we saw 102 consecutive patients (59 male and 43 female, age 31-89 years) with primary GI lymphoma: gastric MALT lymphoma = 76 (63 stage I, 6 stage II, 7 stage III/IV); secondary high grade MALT lymphoma = 3; diffuse large B-cell lymphoma (DLBCL) = 14 (Stage I/II/III-IV = 8/4/2); Burkitt lymphoma = 1; intestinal follicular lymphoma (FL) grade I/II = 8 (stage I/II/III-IV = 5/1/2). Treatment strategies were as follows:MALT-lymphoma: H. pylori eradication, radiation (RTx) and/or chemotherapy (CTx) in stages . II or in case of eradication failure; DLBCL: CTx except in 3 cases treated by H. pylori eradication only; FL: no therapy, CTx or RTx. Results: 26/47 patients (55%) with MALT lymphoma achieved complete remission (CR) after exclusive H. pylori eradication. Application of all therapeutic procedures resulted in CR = 53/76 (70%) and PR with watch-and-wait = 22/76 (29%). There was only 1 patient revealing progression. In DLBCL, 12 (86%) achieved CR after 1-3 line therapies. In FL, watch-and-wait resulted in long-term stable disease in n=5, CR after RTx in 1 case, and stable disease after CTx in 2 cases. Conclusion: Despite a negative selection of patients being presented to our reference center the overall treatment results in all subgroups of GI lymphoma are excellent when all treatment options are offered in a sequential therapy strategy. Watch-and-wait is a promising approach in MALT lymphoma with residual disease following H. pylori eradication and in FL.

Inhibition of Caspase-8 Activity Caused by Overexpression of BCL10 Contributes to the Pathogenesis of High-Grade MALT Lymphoma,

Abstract 3694Mucosa-associated lymphoid tissue (MALT) lymphoma comprises approximately 8% of all non-Hodgkin lymphomas and is the most common lymphoma in the gastrointestinal tract. B-cell lymphoma/leukemia 10 (BCL10) overexpression and nuclear expression has been associated with high-grade MALT lymphomas unresponsive to H. pylori eradication treatment. To explore the molecular mechanism of BCL10 overexpression on the pathogenesis and malignant phenotype of MALT lymphoma, we generated EμSR-BCL10 transgenic mice. Results in our previous report showed that predisposition to marginal zone B-cell lymphoma (MZL) development was enhanced in these transgenic mice. MALT lymphoma precursor cells - marginal zone (MZ) B cells - are expanded in BCL10 transgenic mice. Constitutive activation of both canonical and noncanonical NF-κB pathways was identified in these MZ B cells. Elevated expression of BAFF, a NF-κB downstream gene, may be in part responsible for increased tumor cell survival in MALT lymphomas. In this continuing study, quantitative analysis of BCL10 protein levels and the extent of MZ B cell expansion in heterozygous (Tg/+) and homozygous (Tg/Tg) EμSR-BCL10 transgenic mice demonstrated a direct pathogenic effect of BCL10 protein on MALT lymphomagenesis. The activities of caspase-8 and caspase-3, but not caspase-9, were inhibited with increasing BCL10 protein levels in a dose-dependent manner. Apoptosis induced by anti-IgM was selectively inhibited in MZ B cells from transgenic mice, but no differences were observed following treatment with dexamethasone, γ-irradiation or anti-CD95, implying that overexpressed BCL10 exerts anti-apoptotic effects through the B-cell antigen receptor pathway. Expression of API2, another NF-κB downstream gene, was also elevated in a dose-dependent manner with BCL10 protein level in the MZ B cells. Overexpressed BCL10 protein co-immunoprecipitated with caspase-8 and API2, suggesting an in vivo interaction leading to inhibition of caspase-8 activity. Our current data suggests a novel effect of overexpressed BCL10 in the pathogenesis of high-grade MALT lymphoma by increasing expression of API2 and recruitment of API2 and caspase-8 to form a protein complex leading to the suppression of caspase-8 activity in MZ B cells. Disclosures:No relevant conflicts of interest to declare.

Inhibition of caspase‐8 activity caused by overexpression of bcl10 contributes to the pathogenesis of high‐grade MALT lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma comprises approximately 8% of all non-Hodgkin lymphomas and is the most common lymphoma in the gastro-intestinal tract. It is caused by genetic abnormalities or bacterial infections/chronic inflammation. B-cell lymphoma/leukemia 10 (BCL10) overexpression and nuclear expression have been associated with high-grade MALT lymphomas with genetic abnormalities that are unresponsive to Helicobacter pylori eradication treatment. To explore the molecular mechanism of BCL10 overexpression on the pathogenesis and malignant phenotype of MALT lymphoma, we generated EµSR-BCL10 transgenic mice. By generation of heterozygous and homozygous EuSR-BCL10 mice and showing BCL10 expression levels in these mice, we quantitatively examined relation of MZ B cell expansion and inhibition of caspase-8 activity with BCL10 protein level. We also investigated API2 and caspase-8 expression by Western blot and their interaction with BCL10 by co-immunoprecipitation. MZ B-cell expansion is directly related to BCL10 protein level in a dose-dependent manner. The activity of caspases-8 and -3, but not caspase-9, was inhibited with increasing of BCL10 protein level. Expanded MZ B cells showed selective survival under stimulation of anti-immunoglobulin M, but not dexamethasone, γ-irradiation, or anti-CD95, implying that overexpressed BCL10 exerts anti-apoptotic effects through B-cell antigen receptor (BCR) pathway. Overexpressed BCL10 protein co-immunoprecipitated with caspase-8 and API2 protein, suggesting an in vivo interaction of them. Our data demonstrate a novel effect of overexpressed BCL10 in the pathogenesis of high-grade MALT lymphoma by increasing expression of API2 and it then forming a protein complex with BCL10/caspase-8 leading to caspase-8 activity suppression.

Molecular Mechanism of Gastric MALT Lymphoma Formation by Helicobacter heilmannii Infection

liver. Twelve and eighteen months after the infection, approximately 100% of infected mice had liver and pulmonary lesions. Some of the MALT lymphomas were defined as belonging to the high-grade group by the PCNA positivity. Eradication of the bacteria induced shrinkage of the tumor in the liver and the lung with apoptotic cells as well as in the stomach. Conclusion: Long-term infection with Helicobacter heilmannii in C57BL/6 mouse induced lowand high-grade hepatic and pulmonary MALT lymphoma as well as gastric lymphoma. Eradication of the bacteria brought about shrinkage of the hepatic and pulmonary lesions as well as gastric MALT lymphoma.

MALT Lymphoma Stem Cells in H. Heilmannii-Infected Mice

liver. Twelve and eighteen months after the infection, approximately 100% of infected mice had liver and pulmonary lesions. Some of the MALT lymphomas were defined as belonging to the high-grade group by the PCNA positivity. Eradication of the bacteria induced shrinkage of the tumor in the liver and the lung with apoptotic cells as well as in the stomach. Conclusion: Long-term infection with Helicobacter heilmannii in C57BL/6 mouse induced lowand high-grade hepatic and pulmonary MALT lymphoma as well as gastric lymphoma. Eradication of the bacteria brought about shrinkage of the hepatic and pulmonary lesions as well as gastric MALT lymphoma.

Diagnosis and Treatment of Gastric MALT Lymphoma

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma represents approximately 40% of gastric lymphomas, and its incidence is increasing. An early diagnosis for gastric MALT lymphoma is important, but not easy due to non-specific symptoms and endoscopic findings. Diagnosis is based on the histopathologic evaluation of multiple, deep and repeated biopsies taken from normal and any abnormal appearing sites of the stomach. In addition, the presence of Helicobacter pylori (H. pylori) infection must be determined to determine therapeutic approach. Endoscopic ultrasonography (EUS) is essential for the evaluation of regional lymph nodes and the depth of tumor invasion in the gastric wall, for predicting response to H. pylori eradication, and for monitoring tumor regression or recurrence. The eradication of H. pylori is recommended as an initial treatment for low-grade gastric MALT lymphoma with H. pylori infection. Both radiation therapy and chemotherapy are suitable alternative options for H. pylori-negative, refractory, or high-grade gastric MALT lymphoma. But, the role of surgery is diminishing. After treatment, strict endoscopic regular follow-up including EUS is recommended with multiple biopsies. However, controversy remains regarding the best diagnosis, treatment and follow-up strategy for this disease.

Accumulation of aberrant CpG hypermethylation by Helicobacter pylori infection promotes development and progression of gastric MALT lymphoma

Aberrant DNA hypermethylation is an important mechanism for the inactivation of tumor-related genes in human tumors. Gastric mucosa-associated lymphoid tissue (MALT) lymphomas arise from Helicobacter pylori-associated chronic gastritis; most patients are H. pylori-positive and eradication therapy is highly effective. In the present study, we used methylation-specific PCR to analyze the DNA methylation status of 11 tumor-related genes (Kip2, p16, hMLH-1, p15, p73, MGMT, DAPK, MINT1, MINT2, MINT31 and HCAD) in 21 specimens of MALT lymphoma, 5 specimens of MALT lymphoma with large cell component (high-grade MALT lymphoma), 15 specimens of diffuse large B-cell lymphoma (DLBCL), 8 specimens of complete remission of MALT lymphoma after eradication therapy, 5 specimens with no evidence of malignancy and PBMCs from 10 healthy donors. The average number of methylated genes was significantly greater in gastric lymphomas as compared to normal controls (P<0.001). The CpG island methylator phenotype (CIMP) was observed in 93.3% (14/15) of DLBCLs, 100% (5/5) of high-grade MALT lymphomas and 61.9% (13/21) of MALT lymphomas; in contrast, CIMP was not found in the control group (0%). The average number of methylated genes and the CIMP incidence significantly increased with H. pylori infection. Furthermore, aberrant CpG methylation of specific genes, such as p16, MGMT and MINT31, was consistently associated with H. pylori infection. These findings strongly suggest that H. pylori infection causes the aberrant DNA hypermethylation of specific genes and induces CIMP, which is an important epigenetic mechanism for the development and progression of gastric MALT lymphoma; additionally, our findings provide new epigenetic markers.

Clinicopathologic Study of Chromosomal Aberrations in Gastric Lymphomas of Korean Patients

Background : The incidence and clinical correlation of MALT1 translocation and numerical aberrations in Korean gastric MALT lymphoma patients have been rarely reported. We studied the incidence and clinicopathologic relationship of these chromosomal aberrations in Korean gastric lymphomas. Methods : Seventy-six gastric lymphomas, which consisted of 40 low grade MALT lymphoma, 4 high grade MALT lymphoma and 32 diffuse large B-cell lymphoma (DLBCL) cases, were analyzed for the detection of t(11;18) API2-MALT1, t(14;18) IgH-MALT1 and aneuploidies of chromosomes 3 or 18 using fluorescence in situ hybridization. Results : The t(11;18) was demonstrated in 3 low grade MALT lymphomas (7.5%) and one DLBCL, which was associated with advanced stage, deeper invasion, and disease progression or relapse. The t(14;18) was demonstrated in none of these cases. Trisomy 3 and 18 were detected in 8 (11%) and 11 of 76 cases (12.5%) respectively, and found only in translocation-negative cases. Two of 4 high grade MALT lymphomas showed trisomy 18. All patients survived with successful second treatment after progression or relapse. Conclusions : The t(11;18) API2-MALT1 was not quite frequent in Korean low grade gastric MALT lymphomas and was associated with advanced clinical situations. Overall prognosis was good for long-term follow-up regardless of progression or relapse.

Mucosa-associated lymphoid tissue lymphoma of the ileum as the cause of an intestinal invagination

We herein report a case of a 14-year-old male with mucosa-associated lymphoid tissue (MALT) lymphoma of the ileum as the cause of an intestinal intussusception. The patient was referred to the hospital with abdominal pain and dyspeptic complaints and was operated on with a prediagnosis of acute abdomen. Abdominal exploration revealed an ileoileal intussusception induced by a 2-cm tumor. A segmental ileal resection was done at the operation. The histopathologic examination of the specimen revealed atypical lymphocytes starting from the mucosae infiltrating the muscular layer and the serosae. Based on these findings, the tumor was diagnosed as a high-grade MALT lymphoma. The patient recovered uneventfully after the surgery, and chemotherapy was started.

Translocation (11; 18) and Gastric High Grade Lymphoma Risk

Purpose: Translocation t (11; 18) (q21; q21) is the most frequent chromosomal aberration in extranodal marginal zone lymphoma of the MALT type. This translocation has been associated with an aggressive course but has not been described in high grade gastric MALT lymphoma. Some authors propose that tumors with this translocation rarely or never progress to high grade lymphomas. However, these conclusions are based on examining few specimens. This study examines the frequency of chromosomal translocation t (11; 18) (q21; q21) in lymphomas from patients with low grade and high grade marginal zone lymphoma of the MALT type. Methods: We examined paraffin embedded tissue of patients with gastric marginal lymphoma of MALT type. The presence of the t (11; 18) (q21; q21) was determined using reverse transcription-polymerase chain reaction (RT-PCR); B-actin transcript was amplified to ensure specimen adequacy. Results: We examined 64 paraffin-embedded gastric lymphomas (39 high-grade MALT lymphomas and 22 low-grade MALT lymphomas) from Italy, USA and Japan. The actin transcript was amplified in 61 of 64 cases (95.3%). The t (11; 18) translocation was detected in 21% (8 of 39) cases with high-grade MALT lymphoma vs. 4 of 22 (18%) with low-grade MALT lymphoma [odds 0.861, 95% CI 0.227–3.267]. Conclusions: Translocation t (11; 18) (q21; q21) is characteristic of extra nodal marginal lymphomas of MALT type. It was found in both low-grade and high-grade gastric lymphomas of the MALT type at an approximately same frequency. These results challenges the assumptions that this translocation is absent in high grade lymphoma or that the translocation precludes its progression to high grade lymphoma. Testing for the translocation may provide additional prognostic information or help identify a subgroup where close follow is needed.

Treatment of gastric mucosa-associated lymphoid tissue lymphoma: Helicobacter pylori eradication and beyond

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the paradigm of lymphomas developing in extranodal areas after antigen stimulation. In the stomach, Helicobacter pylori colonization induces the appearance of MALT and, eventually, MALT-derived lymphoma. This type of lymphoma is initially a localized form of disease, but may disseminate and transform into high-grade lymphoma, making full staging (as for nodal lymphomas) and endoscopic ultrasonography to evaluate the penetration of the lymphoma through the gastric wall mandatory. In localized gastric MALT lymphoma, the first step in treatment is eradication of H. pylori, which results in 60–90% regression. This response is maintained for years in most patients, with only 10–15% relapse, frequently precipitated by H. pylori reinfection. A component of high-grade lymphoma, penetration to gastric serosa or beyond and translocation t(11;18) are the main factors that make lymphoma resistant to eradication. Surgery or radiotherapy can cure localized lymphomas in 75–90% of patients. Chemotherapy with alkylating agents, combination chemotherapy and purine analogs, and anti-CD20 antibodies can also induce remission of localized lymphomas refractory to eradication, as well as locally advanced and disseminated lymphomas. The optimum chemotherapy treatment for advanced disease has not yet been established; however, combination therapy, including purine analogs with or without anti-CD20, may be a promising option. Despite histological responses and prolonged remissions, residual molecular disease can be demonstrated in most cases treated with H. pylori eradication, radiotherapy or alkylating agents, and even after more intense chemotherapy, although this does not seem to lead to late relapses. High-grade gastric MALT lymphoma should be treated with chemotherapy, with cyclophosphamide, doxorubicin, oncovin and prednisone being the best first-line option. All gastric MALT lymphomas associated with H. pylori should receive eradication treatment in addition to other required treatment.

Surgery and Chemotherapy versus Chemotherapy as Treatment of High-Grade MALT Gastric Lymphoma

Treatment of high-grade MALT (mucosa-associated lymphoid tissue) gastric lymphoma remains uncertain. To assess efficacy and toxicity of the most common therapies--surgery followed by chemotherapy or chemotherapy alone--we began a controlled clinical trial in patients in early stage (I and II 1). One hundred and two patients were randomized to be treated with surgery followed by six cycles of CEOP-Bleo (cyclophosphamide, epirubicin, vincristine, prednisone, and bleomycin at standard doses) (52 cases) or with chemotherapy alone (49 cases). Complete response rates were 94% [95% confidence interval (CI): 88-99%] and 96% (93-100%), respectively. Actuarial curves at 5 yr showed that event-free survival were 70% (95% CI: 59-74%) in patients treated with surgery and chemotherapy, that were not statistically significant to 67% (95% CI: 51-69%) in the patients who received chemotherapy (p = 0.5). Also, overall survival that was not statistically significant: 78% (95% CI: 70-88%) in the combined treatment and 76% (95% CI: 70-87%) in chemotherapy (p = 0.8). Acute and late toxicity were mild and well controlled. No acute leukemia or second neoplasm has been observed. The use of surgery and chemotherapy did not improve outcome in patients with early-stage high-grade gastric MALT lymphoma. It is apparent that chemotherapy alone is sufficient treatment in this select group of patients.

High-grade Hepatic Mucosa-associated Lymphoid Tissue (MALT) Lymphoma Probably Transformed from the Low-grade Gastric MALT Lymphoma

The Mucosa-associated lymphoid tissue (MALT) lymphoma, which was first described in 1983, is known to be caused by chronic Helicobacter pylori (HP) infection, which triggers lymphoid infiltration and formation of organized lymphoid tissue. In approximately two thirds of cases of MALT, the lymphoma has been observed to regress after treatment of H. pylori infection; this provides strong evidence of a causative role of HP in the etiology of MALT. We report a case of a 67-year-old female patient with a high-grade MALT lymphoma of the liver; this occurred six years after complete remission of a low-grade gastric MALT lymphoma and after complete eradication of H. pylori. there was no recurrence of the previous low-grade gastric MALT lymphoma. Based on radiological and pathologic findings, the high-grade MALT was considered to result from transformation of the low-grade gastric MALT lymphoma.

Primary gastric lymphoma in Jordan with special emphasis on descriptive epidemiology

The aim of this study was to examine the clinicopathological features and epidemiology of primary gastric lymphoma in Jordan as a model for Middle East countries where such data is scarce. From 1991--2002, 219 patients with primary gastric malignancy were managed at our hospitals. Among these there were 19 patients with primary gastric lymphoma. Pertinent data for these patients were analyzed. Primary gastric lymphoma constituted 65.5% of all gastrointestinal lymphoma and 8.7% of all gastric malignancies. Male-to-female ratio was 2.8:1. The mean age was 56 years (range 39--82). The incidence was 0.6/100,000. The proximal third was the most common localisation. Abdominal pain was the commonest presentation. Low-grade MALT lymphomas, high-grade MALT lymphomas, diffuse large cell B lymphomas and T cell lymphoma were found in 21.1, 26.3, 47.4 and 5.3%, respectively. Nine patients had gastrectomy followed by chemotherapy, 6 patients had palliative resection, 3 patients had chemotherapy only and the remaining patient was treated with Helicobacter pylori eradication. The mean follow-up for all patients was 42.2 months. The 5-year survival rates for stages IE (n=5), IIE (n=4), IIIE (n=6) and IVE (n=4) were 100, 67, 27 and 0%, respectively (p=0.0003). The overall 5 years survival was 48.2%. Primary gastric lymphoma in Jordan shares some epidemiological features with western disease. Jordanian patients are detected and treated after a relatively long delay. Advanced stage at diagnosis correlated with poor outcome. There is a need of an earlier diagnosis and subsequent better care.

Expression of CD86 and increased infiltration of NK cells are associated withHelicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori (H pylori)-dependent. However, unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori-specific intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 (B7.2) and the infiltration of CD56 (+) natural killer (NK) cells can be useful markers to predict H pylori-dependent status of high-grade gastric MALT lymphoma. Lymphoma biopsies from 26 patients who had participated in a prospective study of H pylori-eradication for stage I(E) high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade II or less after H pylori eradication were classified as H pylori-dependent; others were classified as H pylori-independent. The infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry. There were 16 H pylori-dependent and 10 H pylori-independent cases. CD86 expression was detected in 11 (68.8%) of 16 H pylori-dependent cases but in none of 10 H pylori-independent cases (P = 0.001). H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 (+) NK cells than H pylori-independent cases (2.8+/-1.4% vs 1.1+/-0.8%; P = 0.003). CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 (+) NK cells compared to CD86-negative cases (2.9+/-1.1% vs 1.4+/-1.3%; P = 0.005). These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with H pylori-dependent state of early-stage high-grade gastric MALT lymphomas.

Interobserver variation in the histopathological assessment of malt/malt lymphoma: towards a consensus

Background: The classification of mucosa associated lymphoid tissue (MALT) lymphoma is based on characteristic morphologic and immunophenotypic patterns, with distinctive chromosomal aberrations. The critical first step is diagnosis on evaluating H&E-stained sections. We performed an inter-observer study to determine the degree of agreement among pathologists in evaluating gastric lymphocytic infiltrates for MALT lymphoma. Methods: A set of 41 H&E-stained gastric sections (36 endoscopic biopsies and 5 surgically resected sections) that ranged from simple gastritis to primary gastric lymphoma was reviewed separately and independently by 17 participants including hematopathologists, pathologists with a special interest in gastrointestinal pathology, and general pathologists. The participants were from the United States, Europe, and Japan. Results were entered into a standardized data collection form and the results were analyzed using κ statistics. Monte Carlo simulation was used to adjust for multiple biases. Results: Overall, interobserver reproducibility in the morphologic evaluation of gastric MALT was suboptimal. The κappa statistic was 0.3 for simple gastritis, low-grade MALT and for high grade MALT lymphoma. Monte Carlo simulation suggested that the degree of disagreement was directly related to the pathologist's experience in evaluating gastric biopsies for MALT lesions. However, after conjointly reviewing all cases, the Houston workshop agreed on findings that would increase the reproducibility of diagnosis, especially for pathologists with limited experience with this disease. These included the availability of macroscopic data, extensive sampling, the presence of lymphoepithelial lesions, immunophenotyping and particularly abnormal mucosa localization of B-cells, in addition to other molecular finding such as monoclonality and translocationt (11;18). The group also agreed on the need for standardizing the terminology currently used to facilitate future comparison between studies. Conclusions: Though the study shows poor agreement on morphologic MALT lymphoma categorization, the Houston workshop suggested recommendations that should increase the diagnostic accuracy and reproducibility of MALT lymphoma diagnosis. A follow up workshop will be organized to measure the diagnostic reproducibility for MALT lymphoma using the suggested recommendations.

Nuclear expression of BCL10 or nuclear factor kappa B predicts Helicobacter pylori-independent status of early-stage, high-grade gastric mucosa-associated lymphoid tissue lymphomas.

A high percentage of early-stage, high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori dependent. t(11;18)(q21;q21), a genetic aberration highly predictive of H. pylori-independent status in low-grade gastric MALT lymphoma, is rarely detected in its high-grade counterpart. This study examined whether nuclear expression of BCL10 or nuclear factor kappa B (NF-kappaB) is useful in predicting H. pylori-independent status in patients with stage IE high-grade gastric MALT lymphomas. Twenty-two patients who had participated in a prospective study of H. pylori eradication for stage IE high-grade gastric MALT lymphomas were studied. The expression of BCL10 and NF-kappaB in pretreatment paraffin-embedded lymphoma tissues was evaluated by immunohistochemistry and confocal immunofluorescence microscopy. The presence of t(11;18)(q21;q21) was identified by a multiplex reverse transcriptase polymerase chain reaction of the API2-MALT1 chimeric transcript. Aberrant nuclear expression of BCL10 was detected in seven (87.5%) of eight H. pylori-independent and in none of 14 H. pylori-dependent high-grade gastric MALT lymphomas (P <.001). All seven patients with nuclear BCL10 expression had nuclear expression of NF-kappaB, compared with only two of 15 patients without nuclear BCL10 expression (P =.002). As a single variable, the frequency of nuclear expression of NF-kappaB was also significantly higher in H. pylori-independent tumors than in H. pylori-dependent tumors (seven of eight [87.5%] v two of 15 [12.3%]; P =.002). The API2-MALT1 fusion transcript was detected in only one (12.5%) of eight H. pylori-independent lymphomas. Nuclear expression of BCL10 or NF-kappaB is highly predictive of H. pylori-independent status in high-grade gastric MALT lymphoma, and coexpression of these two markers in the nuclei is frequent.