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PubMed1995

Gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. Clinicopathological study and evaluation of the prognostic factors in 143 patients.

BACKGROUND: Gastric MALT lymphoma can be histologically classified into two groups, low-grade (LG) and high-grade (HG); however, their natural history is poorly understood. We have studied a large retrospective series aiming to confirm whether the histological groups confer different clinical features and behavior and to analyze the prognostic factors in these patients. PATIENTS AND METHODS: A series of 143 gastric B-cell MALT lymphomas is reported. Eighty-four were low-grade lymphomas (LG) and 59 were high-grade lymphomas (HG). Median follow-up was 36 months. The clinical and analytical parameters of the 84 LG patients were compared with those of the 59 HG patients. In the patients who had been operated on, the pathological features (macroscopical patterns, tumor size, involvement of resection margins, degree of parietal invasion and involvement of abdominal lymph nodes and adjacent viscera) of the LG patients were compared with those of the HG patients. The sites of relapses were studied. In the 132 treated and followed-up patients the influence of the treatment and that of clinical, analytical and pathological features on survival were investigated with the Kaplan and Meier and log-rank tests. To identify the factors with independent influence on survival, a Cox model was fitted for the whole series and separately for 53 HG patients. RESULTS: HG group differed from the LG group by a significantly higher frequency of weight loss at presentation, palpable abdominal mass, hepatomegaly, peripheral lymphadenopathy, elevated serum LDH, higher incidence of stage III-IV and tumor/mass patterns in the endoscopy and in the gastrectomy specimen. The tumor was significantly larger in the HG group than in the LG and the deeper invasion of the gastric wall, the higher frequency of infiltration of the abdominal lymph nodes and the visceral extension were also significant in the HG group. Complete remission (CR) was achieved in 91% of the patients of the LG group, but was significantly lower, 70%, in the HG group. Relapses occurred in the stomach and also in non-MALT sites. In 132 treated and followed-up patients, elevated serum LDH, absence of CR, HG group and stage III-IV were associated with a worse survival. In the Cox multivariate model, stage was the only variable influencing survival, although stage was related to the histological grade. In the HG group, stage was also an independent significant risk factor, whereas treatment with surgery, chemotherapy or both was not. In the 103 patients treated with surgery, a worse survival was associated with the involvement of the resection borders, depth of the infiltration of the gastric wall, dissemination to distant abdominal nodes and adjacent organs, but not with the addition of chemotherapy. CONCLUSIONS: Histological classification into LG and HG separates distinctive groups of gastric MALT lymphoma that show striking clinical and prognostic differences. Besides histological grade, stage is the most important prognostic feature.

Aged↗
PubMed1995

High incidence of other neoplasms in patients with low-grade gastric MALT lymphoma.

BACKGROUND: Low-grade gastric MALT lymphoma is an uncommon tumour for which a close association with chronic Helicobacter pylori infection has been suggested. However, given the rarity of MALT lymphoma of the stomach despite the high prevalence of H. pylori infection, it seems plausible that genetic host factors might play a fundamental role in gastric lymphomagenesis. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 83 patients with low-grade gastric MALT, all of whom resided in a geographic area (southern Switzerland and northern Italy) where the incidence of gastric tumours appears to be uncommonly high. RESULTS: One or more additional cancers were observed in 17 of 83 patients (20%, 95% CI 12% to 31%) for a total of 23 tumours. Of these, 5 were diagnosed prior to, 12 concomitantly with, and 7 after the gastric MALT lymphoma. Eleven patients had a single additional solid tumour (13%, 95% CI 7% to 22%); 3 patients had non-Hodgkin's lymphoma and one had Hodgkin's disease. Multiple additional cancers were present in 3 cases. Nine of 83 patients have died and 8 of them of a second cancer. CONCLUSIONS: Unexpectedly an extraordinarily large number of patients with other malignancies was observed in this series. The reasons for this finding are still unknown, but genetic alterations are speculated to play an important role.

Female↗
PubMed1995

Pulmonary malignant lymphoma of mucosa-associated lymphoid tissue (MALT) arising in a pediatric HIV-positive patient.

A malignant lymphoma arising in the lung of a pediatric HIV-positive patient exhibited histologic and clinical features of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Clinically, the neoplasm consisted of a 4-cm mass in the left-upper lobe of the lung of a 7-year-old girl. The lung mass was surgically resected. Monoclonal immunoglobulin heavy and light chain gene rearrangements were shown by Southern blot. Monoclonality of light chain expression was demonstrated by immunohistochemistry. Coexpression of Leu-22 (CD43) by the tumor cells supported the diagnosis of lymphoma. The remainder of the pulmonary parenchyma distal to the mass was associated with pulmonary lymphoid hyperplasia/lymphocytic interstitial pneumonitis, which may have been a predisposing factor. Gastric MALT lymphomas have recently been described in adult HIV-antibody-positive patients. Ours represents the first reported case of a pulmonary MALT lymphoma in a pediatric HIV-positive patient. In addition, at age 7, this is the youngest patient reported with a MALT lymphoma.

Child↗
PubMed1997

Malignant lymphoma of the bladder: evidence from 36 cases that low-grade lymphoma of the MALT-type is the most common primary bladder lymphoma.

Patients with malignant lymphoma of the bladder were studied, and three clinical groups were defined: those with primary lymphoma localized in the bladder, lymphoma presenting in the bladder as the first sign of disseminated disease (nonlocalized lymphoma), and recurrent bladder involvement by lymphoma in patients with a history of malignant lymphoma (secondary lymphoma). The differences in these groups regarding lymphoma type, clinical presentation, and clinical outcome were studied. Mayo Clinic Tissue Registry records from 1940 to 1996 were searched to identify patients with lymphomas involving the bladder. The lymphomas were classified based on review of the histology and immunophenotype performed by immunoperoxidase methods. Clinical records were reviewed. Presenting symptoms included urinary frequency, dysuria, hematuria, and lower abdominal and back pain. Primary lymphoma was present in six patients. All were B-cell lineage low-grade lymphomas of the mucosa-associated lymphoid tissue (MALT) type. No patient had recurrent lymphoma or died of lymphoma. Nonlocalized bladder lymphoma occurred in 17 patients; one with low-grade lymphoma of the MALT type, four with follicle center lymphomas, and 12 with large cell lymphomas. Excluding two patients who died postoperatively, median survival was 9 years. Six patients died of lymphoma in the follow-up period. Secondary bladder lymphoma occurred in 13 patients: two with low-grade lymphoma of the MALT type, one with follicle center lymphoma, one with mantle cell lymphoma, and nine with diffuse large cell lymphomas. Median survival in this group was 0.6 years. Low-grade lymphoma of the MALT type was the most frequent type of primary bladder lymphoma and was associated with an excellent prognosis. The bladder can be the presenting site of lymphomatous involvement in patients with more widespread disease. Survival in this group is quite favorable and is presumably dependent on lymphoma histologic type, stage of disease, and other prognostic factors. Bladder involvement by recurrent lymphoma is a sign of widely disseminated disease and is associated with a very poor prognosis.

Adult↗
PubMed2001

Pathologic and clinical features of primary pulmonary extranodal marginal zone B-cell lymphoma of MALT type.

We reviewed pathologic, phenotypic, and clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type primarily involving lung to address unresolved questions regarding behavior and pathologic features of unambiguously diagnosed pulmonary MALT lymphoma. Lung specimens from 50 patients were reviewed. Forty-one had low-grade MALT lymphoma. Nine had low-grade MALT lymphoma and diffuse large B-cell lymphoma. The patients included 32 women and 18 men with a median age of 68 years (range 34-88 years). Half of the patients were asymptomatic at the time lymphoma was diagnosed. Radiographic abnormalities were more commonly unilateral (37 patients) than bilateral (12 patients). Localized masses or nodules occurred in 39 patients. Associated autoimmune disorders (29%) and monoclonal gammopathies (43%) were common. Low-grade lymphomas formed intraparenchymal masses composed of centrocyte-like cells, plasmacytoid lymphocytes, and plasma cells that formed lymphoepithelial lesions and exhibited a lymphangitic growth pattern. Mediastinal lymph nodes were involved histologically in 44% of cases. Lymphoma-specific survival was 71.7% at 10 years, and overall survival was significantly worse than age-and gender-matched control patients. None of the following features predicted those patients who had an adverse outcome: systemic symptoms, presence of autoimmune disorders or paraproteinemia, anatomic distribution and number of pulmonary lesions, lymph node involvement, or presence of anthracycline-treated large B-cell lymphoma.

Adult↗
PubMed2004

Combination of adult inclusion conjunctivitis and mucosa-associated lymphoid tissue (MALT) lymphoma in a young adult.

PURPOSE: To report a patient who was diagnosed with combined adult inclusion conjunctivitis (AIC) and mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: This is a case report. RESULTS: An 18-year-old male patient presented with chronic conjunctivitis and giant follicles. Evaluation by chlamydial antigen assay was positive. Conjunctival biopsy for the immunohistochemical stain and polymerase chain reaction of the left eye showed MALT lymphoma. CONCLUSIONS: MALT lymphoma can masquerade as other ocular surface diseases. Chlamydial infection causes chronic inflammation of the conjunctiva. Both of these diseases should be considered as a differential diagnosis of refractory follicular conjunctivitis. It is worthy of further study to determine whether chronic inflammation resulting from chlamydial infection increases the risk of MALT lymphoma or it is coincidental.

Adolescent↗
PubMed2001

Detection of t(I 1; 18) in MALT-type lymphoma with dual-color fluorescence in situ hybridization and reverse transcriptase-polymerase chain reaction analysis.

t(11:8) is a recurrent chromosomal abnormality observed in mucosa-associated lymphoid tissue (MALT)-type lymphoma. API2 and MLT genes have been implicated. The authors devised a dual-color interphase fluorescence in situ hybridization (FISH) system to detect splitting of 11q22 and its fusion with 18q21. Subjects were 44 cases of extranodal lymphoma and cases of primary macroglobulinemia. Whenever RNA was available, reverse transcriptase-polymerase chain reaction followed by sequence analysis was performed. Positive cases by dual-color FISH analysis were restricted to MALT-type lymphoma and one case of primary macroglobulinemia. Among 24 cases of MALT-type lymphoma, 14 (58%) (4 gastric, 5 pulmonary, 3 orbital, 1 salivary, and 1 thyroid lymphomas) had splitting of the 11q22 region probes and fusion of signals suggesting the translocation of chromosome 11 and 18. Reverse transcriptase-polymerase chain reaction analysis showed the API2/MLT gene fusion in 9 of 10 cases. Sequence analyses showed three different modes of involvement of the MLT gene, whereas the breakpoint at API2 was the same. Monoclonal component of serum immunoglobulin M was observed in 3 of 14 positive cases for the translocation. Direct visualization using dual-color FISH on samples serves as a molecular tool for management of MALT-type lymphoma with API2/MLT gene fusion.

Adult↗
PubMed1999

Seroprevalence of eight Helicobacter pylori antigens among 182 patients with peptic ulcer, MALT gastric lymphoma or non-ulcer dyspepsia. Higher rate of seroreactivity against CagA and 35-kDa antigens in patients with peptic ulcer originating from Europe and Africa.

BACKGROUND: It has been suggested that Helicobacter pylori may induce more or less severe gastroduodenal disease according to the strain virulence. DESIGN: We used Western blot to determine antigenic profiles associated with duodenal or gastric ulcer disease, MALT lymphoma and non-ulcer dyspepsia, and to identify geographical differences. METHODS: One hundred and eighty-two consecutive patients with H. pylori infection were studied. H. pylori infection was diagnosed by a rapid urease test or histological examination of gastric biopsy samples. Bacterial density and gastritis were assessed histologically by using the Sydney scoring system. Western blot was used to identify antibodies against eight antigens (CagA, VacA, urease A, heat shock protein B, and 19.5, 26.5, 30 and 35 kDa). Patients were questioned on their smoking habits and place of birth and childhood. RESULTS: There were 73 patients with duodenal ulcer, 30 with gastric ulcer, eight with erosive duodenitis, 17 with gastric MALT lymphoma and 54 with non-ulcer dyspepsia. Most (>85%) were seropositive for the heat shock protein B and 26.5-kDa antigens. The prevalence of the other antigens ranged from 45% (VacA) to 68% (urease B). The seroprevalence of CagA antigen was significantly higher (P < 0.01) in cases of gastroduodenal ulcer (84%) than non-ulcer dyspepsia (37%). Similarly, 35-kDa antigen reactivity was more frequent (P < 0.05) in duodenal ulcer patients (75%) than in those with non-ulcer dyspepsia (50%). The antigenic profiles associated with MALT gastric lymphoma and non-ulcer dyspepsia were similar. Multivariate analysis showed that only gastroduodenal ulcer was significantly associated with CagA. Gastroduodenal ulcer and a childhood spent in Africa were both associated with 35-kDa and combined CagA-35-kDa reactivity. CONCLUSIONS: This study confirms the strong seroprevalence of H. pylori CagA antigen and shows a high prevalence of the 35-kDa antigen in patients with gastroduodenal ulcer, especially those raised in Africa. There was no difference in the serological pattern between patients with non-ulcer dyspepsia and those with MALT lymphoma. Tests for antibodies to the CagA-35-kDa antigen combination might be used to select H. pylori-infected dyspeptic patients warranting treatment.

Africa↗
PubMed2006

Primary mucosa-associated lymphoid tissue (MALT) lymphoma occurring in the rectum: a case report and review of the literature.

The primary extranodal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a distinct clinical pathologic entity that develops in diverse anatomic locations such as the stomach, salivary gland, thyroid, lung, and breast; however, colorectal involvement is rare. To the best of our knowledge, only 30 cases of primary rectal MALT lymphoma have been published in the English language literature, mostly from Japan. A single case has been reported from the US before this report. The most common symptoms ranged from asymptomatic to occult or gross gastrointestinal bleeding. Simultaneous involvement of the cecum or colon was seen in 20% of the patients. Ninety percent of the patients were classified as low grade, Stage 1 at the time of diagnosis. Polypoid lesions were 10-fold more common than ulcerative lesions. Seven patients were reported to have H pylori in the stomach. The majority of the patients underwent surgical or endoscopic resection as a cure; however, controversy exists with regards to antibiotic treatment or observation alone because of unknown etiopathogenesis. Infection with microorganisms other than H pylori has been postulated in the development of rectal MALT lymphoma; however, this hypothesis remains unproven. The overall prognosis of rectal MALT lymphoma appears favorable; however, long-term follow-up data is lacking. Therefore, periodic clinical monitoring should be done in these patients.

Aged↗
PubMed1995

Heterogeneity of bcl-2 expression in MALT lymphoma.

Bcl-2 protein expression was studied in a series of 58 MALT lymphomas using a monoclonal antibody which recognises this protein in routinely processed paraffin embedded tissue. Thirty-three of 58 cases showed heterogeneity for bcl-2 expression, 18 of 58 cases were bcl-2 positive and 7 of 58 were bcl-2 negative. High grade and low grade MALT lymphomas showed different patterns of staining. All 21 low grade tumours were positive for bcl-2, though in seven cases only a proportion of the neoplastic cells expressed this protein. In the 37 high grade tumours the majority of the neoplastic cells were negative with seven cases showing no reactivity at all. These findings give further support to the theory that MALT lymphomas differ in pathogenesis to nodal lymphomas and suggest that the good prognosis of MALT lymphomas may partly be explained by the fact that they maintain a normal pattern of bcl-2 expression.

Gastrointestinal Neoplasms↗
PubMed1998

Late skin-prick-test reactions to malted wheat. Clinical observations and immunohistochemical characterization.

This study reports late skin-prick-test (SPT) reactions in seven bakers and seven control subjects to malted wheat appearing after 6-10 h, and not preceded by an immediate-phase reaction. Two subjects in each group had a history of atopic symptoms and were Phadiatope positive. Serologic IgE analysis (RAST) of normal wheat flour and of malted wheat grain was negative in all subjects. Skin biopsy specimens were obtained 16-18 h after SPT to malted wheat grain and to histamine and from untested skin. The late SPT reactions in all participants had an urticarial appearance, clinically and in routine histology. Immunohistologically mild to moderate perivascular dermal cell infiltrates were observed in both groups, consisting mainly of CD4+ and HLA-DR+ cells. The number of CD1a+ epidermal cells was statistically significantly higher (P < 0.01) in the bakers' prick-tested skin compared to that of the controls, a fact which might reflect preparedness to react upon challenge. There were no statistical differences between the two groups in IgE+ epidermal cells or epidermal cells expressing the high-affinity IgE receptor (Fc epsilon RI). However, there was a correlation between serum-IgE levels and the number of IgE+ epidermal cells. The late skin reactions observed in both bakers and controls were probably more of an irritant or toxic than immune-mediated nature, but they raise the question of whether skin contact with malted flour contributes to an unfavorable prognosis of hand eczema in bakers.

Adult↗
PubMed2006

Polioencephalomalacia in cattle: a consequence of prolonged feeding barley malt sprouts.

Polioencephalomalacia (PEM) in ruminants has been recognized as a consequence of excess sulphur intake. The present study describes clinical, gross and histopathological findings of PEM following an abrupt change of diet in two ranches housing 2750 dairy and 2300 beef cattle. As a result of severe PEM, 256 cattle died or were slaughtered. Clinical findings included circling, hypersensitivity, excessive salivation, hypermetria, incoordination, blindness and death. The first clinical signs occurred in beef calves (6-8 months old) at a holding facility. Clinical signs of the disorder continued intermittently during the 5-month period in both ranches and were more evident in calves and lactating dairy cows. The affected cattle did not respond to thiamine injections. Clinical signs disappeared gradually following removal of barley malt sprouts from the diet. Although macroscopic lesions were not apparent in the brain tissues of some animals, histopathology typical of PEM was found in most cases: spongiosis in the neuropil and neuronal necrosis, haemorrhage, capillary hyperplasia, fibrinoid degeneration in arterioles, multifocal liquefaction necroses in the grey matter and abundance of gitter cells with vacuolar large cytoplasm. Sulphide in rumen fluid of a clinically affected animal was measured as 1.55 mg/dl, which is considerably higher than that collected from two control cows (mean 0.21 mg/dl). The total sulphur content of the diet containing barley malt sprouts was estimated to be 0.45%, which is also higher than the National Research Council (NRC) maximum tolerable levels. In conclusion, PEM can result from excess barley malt sprout intake because of its higher sulphur content. Clinical signs may occur shortly after the intake of barley malt sprout as outbreaks with a higher number of deaths or as an ongoing periodic condition.

Animal Feed↗
PubMed2006

Abundant transcripts of malting barley identified by serial analysis of gene expression (SAGE).

Serial analysis of gene expression (SAGE) was applied to the major cereal crop barley (Hordeum vulgare) to characterize the transcriptional profile of grain during the malting process. Seven SAGE libraries were generated from seed at different time points during malting, in addition to one library from dry mature seed. A total of 155,206 LongSAGE tags, representing 41,909 unique sequences, was generated. This study reports an in-depth analysis of the most abundant transcripts from each of eight specific time points in a malting barley time course. The 100 most abundant tags from each library were analysed to identify the putative functional role of highly abundant transcripts. The largest functional groups included transcripts coding for stress response and cell defence, ribosomal proteins and storage proteins. The most abundant tag represented B22EL8, a barley metallothionein, which showed significant up-regulation across the malting time course. Considerable changes in the abundance profiles of some of the highly abundant tags occurred at 24 h post-steeping, indicating that it may be an important time point for gene expression changes associated with barley seed germination.

Base Sequence↗
PubMed1997

Primary gastric MALT lymphoma: trivial condition or serious disease?

BACKGROUND: Primary gastric B-cell lymphomas originating from the mucosa-associated lymphoid tissue (MALT) have been demonstrated to be closely associated with Helicobacter pylori infection. Approximately 70% of these tumors regress within 1 year of eradication of H. pylori. Currently, there is little consensus on the best strategies for diagnosing, treating, and following up these lymphomas. Our objective was to review the current strategies for the diagnosis and management of MALT lymphomas and to describe the management guidelines used in our own institution. METHODS: Our approach consisted of a review of the literature and personal experience. RESULTS: Rigorous histopathological criteria (Isaacson's criteria) must be applied to the diagnosis of gastric biopsies with atypical lymphoid aggregates. Molecular and immunohistochemical studies might play have a role in determining the clonality of the lesions, but correlation with the histopathological aspects is crucial. CONCLUSIONS: Little solid information exists on the natural history and evolution of MALT lymphomas. While studies are being carried out, we suggest that even a suspected MALT lymphoma in a gastric biopsy specimen should be treated as a potentially serious condition. The diagnosis should be confirmed by an experienced histopathological laboratory, and H. pylori infection must be sought and treated. Because the response of lymphomas to antibacterial therapy cannot be predicted, close follow-up of affected patients is essential.

Helicobacter Infections↗
PubMed2005

HIV+ MALT lymphoma remission induced by highly active antiretroviral therapy alone.

MALT lymphoma is usually described in association with Helicobacter pylori, HCV, HHV8, Campylobacter jejuni or in a setting of overreactive immunity. In HIV(+) patients, MALT lymphoma is most commonly described in children. We describe here an original case of HIV(+) MALT lymphoma with bronchial, conjuctival and laryngeal involvement for which a clinical and histopathological remission has been obtained with HAART alone. We conclude that HIV, as well as H. pylori, C. jejuni and HCV can target lymphogenesis in MALT lymphoma.

Antiretroviral Therapy, Highly Active↗
PubMed1983

Action of CAP on the malT promoter in vitro.

DNase I footprinting experiments demonstrated that CAP, the cyclic AMP receptor protein of Escherichia coli, binds around position -70 at the promoter of malT, the positive regulator gene of the maltose regulon. The binding of CAP in the presence of cyclic AMP favored the subsequent specific binding of RNA polymerase. Initiation of malT transcription in vitro displayed an absolute requirement for CAP at all tested RNA polymerase concentrations. However this was not the case with a mutant promoter (malTp1), which leads to CAP-independent malT expression in vivo. In that case an effect of CAP was seen only at the lower concentrations of RNA polymerase. These results, which suggest that CAP stimulates malT expression by promoting the binding of polymerase to the promoter, are compared with those obtained in other systems.

Binding Sites↗
PubMed2004

Changes in salivary gland immunohistology and function after rituximab monotherapy in a patient with Sjogren's syndrome and associated MALT lymphoma.

OBJECTIVES: To report the successful use of rituximab on salivary gland immunohistology and function in a patient with Sjogren's syndrome (SS) and associated MALT lymphoma. CASE REPORT: The patient was a 42 year old woman with primary SS and associated MALT lymphoma located in the parotid gland and the hard palate. Four infusions of rituximab (375 mg/m(2)) weekly resulted in complete remission of the lymphoma. An incision biopsy of the parotid gland before and after treatment showed improvement of the (immuno)histopathological characteristics of SS, with possible regeneration of salivary gland tissue. Furthermore, salivary analysis showed decreased inflammatory characteristics and increased stimulated salivary flow. DISCUSSION: Rituximab is a promising agent in the treatment of SS associated MALT lymphoma. In addition to the effect on MALT lymphoma, B cell depletion by rituximab may also attenuate the activity of SS. This case report is the first to describe the effect of rituximab on histological and sialometric/chemical characteristics of SS. The efficacy of rituximab in the treatment of SS warrants further investigation.

Adult↗
PubMed2006

Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the third most common non-Hodgkin lymphoma subtype, accounting for around 6-8% of all non-Hodgkin lymphomas in the Western hemisphere. Although MALT lymphomas are clinically indolent, the disease is typically chronic, requiring long-term clinical surveillance and, often, repeated biopsies. Pathologists thus play a central role in the diagnosis and management of these patients. The optimal diagnosis and management of a MALT lymphoma requires careful integration of morphological, immunohistochemical and molecular information, together with close cooperation with the clinician treating the patient. This review discusses recent developments in the molecular pathogenesis of MALT lymphoma and provides strategies for integrating this information into daily pathological practice.

Algorithms↗