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Background To compare clinicopathologic and molecular characteristics of low-grade gastric mucosa-associated lymphoid tissue lymphoma depending on Helicobacter pylori positivity and to find out a predictive factor for unresponsiveness to Helicobacter pylori eradication therapy in Korea. Methods A total of 53 Helicobacter pylori-positive and 13 negative mucosa-associated lymphoid tissue lymphoma patients were enrolled, and tissues from 21 patients were investigated to examine the presence of t(11;18)(q21;q21) with fluorescence in situ hybridization. Clinicopathologic features such as the endoscopic appearance, dominant site of lesion, depth of invasion, clinical stage, and the existence of MALT1 gene rearrangement were compared between these two groups. Fifty-six patients who underwent H. pylori eradication therapy were divided into responder and nonresponder groups. The two groups were analyzed to calculate odds ratios for resistance to the eradication. Results Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma patients averaged a more advanced clinical stage than H. pylori-positive ( p = .023) patients. The frequency of t(11;18)/ API2- MALT1 did not differ between H. pylori-positive (45.5%) and H. pylori-negative cases (55.6%). Thirty-eight of 51 (74.5%) H. pylori-positive patients achieved complete regression after the eradication, while 2 of 5 (40%) H. pylori-negative patients obtained regression. Presence of lesions in both distal and proximal parts of stomach ( p = .041) and bearing of t(11;18)(q21;q21) ( p = .007) were predictors for nonresponsiveness for H. pylori eradication. Conclusions Helicobacter pylori eradication could be performed as a primary therapy regardless of H. pylori status, and assessing t(11;18)/ API2- MALT1 would be considered after failure to remission by H. pylori eradication. [ABSTRACT FROM AUTHOR]

Primary gastric diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease entity that includes patients with (DLBCL/MALT) and without detectable mucosa-associated lymphoid tissue (MALT) lymphoma components (de novo DLBCL). We sought to evaluate the clinical characteristics and outcome of this disease in a large number of cases. Patients with primary gastric DLBCL ( n = 162) seen on 2001-2011 at the Tianjin Medical University Cancer Institute and Hospital and the First affiliated Hospital of Chinese PLA General Hospital were retrospectively reviewed. The distribution of sex, age, Lugano staging, and other main clinical characteristics was similar between the de novo DLBCL and DLBCL/MALT groups ( p > 0.05). However, the proportion of patients with a stage-modified international prognostic index (m-IPI) ≥ 2 was higher in the de novo DLBCL (34 %) than the DLBCL/MALT group (17 %) ( p = 0.026). In addition, the Helicobacter pylori infection rates were higher in the DLBCL/MALT (75 %) than the de novo DLBCL group (36 %) ( p < 0.001). Five-year progression-free survival (PFS) and overall survival (OS) estimates were similar for patients in the de novo DLBCL ( p = 0.705) and DLBCL/MALT groups ( p = 0.846). Surgical treatment did not offer survival benefits when compared with chemotherapy for 5-year PFS ( p = 0.607) and OS estimates ( p = 0.554). There were no significant differences in 5-year PFS and OS estimates for patients treated with rituximab-chemotherapy ( p = 0.261) or conventional chemotherapy ( p = 0.227). Non-GCB subtype and m-IPI ≥ 2 were independently associated with shorter OS, and advanced stages of lymphoma were independently associated with shorter PFS. [ABSTRACT FROM AUTHOR]

BACKGROUND: In marginal zone lymphoma (MZL), clinical and follow-up data on large cohorts of patients are difficult to obtain. The objective of this single-center, retrospective analysis of a large cohort of 144 patients with MZL was to elucidate the role of prognostic markers, treatments, and outcomes in this disease. METHODS: In total, 144 patients were identified who were diagnosed with MZL at the authors' institution between 2003 and 2010. Data on clinical parameters, treatments, response, and survival were analyzed. In addition, the validity of the International Prognostic Index (IPI) and Follicular Lymphoma International Prognostic Index (FLIPI) prognostic scores were tested in patients with MZL. RESULTS: Among 144 patients with MZL, 96 patients (67%) had extralymph node (extranodal) MZL, 32 patients (22%) had lymph node (nodal) MZL, and 16 patients (11%) had splenic MZL. The 5-year progression-free survival rate was 82% in the nodal MZL group, 88% in the extranodal MZL group, and 74% in the splenic MZL group and did not different between the 3 groups ( P = .60). The 5-year overall survival rate was excellent in all 3 MZL groups (nodal MZL, 89%; extranodal MZL, 92%; splenic MZL, 82%; P = .46). In our cohort, the FLIPI score was a significant prognostic marker: The 5-year progression-free survival rate for patients who had FLIPI scores of 0 to 2 (low or intermediate risk) was excellent at 92%, whereas it was only 62% for patients who had FLIPI scores of 3 to 5 (poor risk; P = .003). Similarly, the 5-year overall survival rate for patients who had FLIPI scores of 0 to 2 was 95%, whereas it was only 62% for patients who had FLIPI scores of 3 to 5 ( P = .0009). CONCLUSIONS: The FLIPI score had strong prognostic value in patients with MZL. Patients who have low-risk or intermediate-risk FLIPI scores have an excellent prognosis, whereas patients with poor-risk FLIPI scores are candidates for novel treatment approaches. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: To date, there is no treatment consensus on mucosa-associated lymphoid tissue (MALT) derived primary pulmonary lymphoma (PPL)., Methods: We identified patients with early-stage MALT-type PPL from the National Cancer Institute's Surveillance, Epidemiology, and End Results program database. The patients were divided into four groups according to treatment modalities: None of surgery or chemotherapy (None) group, Surgery alone group, Chemotherapy alone (Chemo alone) group, and Surgery plus chemotherapy (Surgery + chemo) group. Overall survival (OS) and cancer-specific survival (CSS) were study endpoints. We performed Cox regression analyses, propensity score-matched analyses (PSM) and Kaplan-Meier (KM) survival curves to compare the survival among different groups., Results: A total of 953 patients were included in our analysis with 302, 403, 175, and 73 cases in the None, Surgery alone, Chemo alone, and Surgery + chemo groups, respectively. In this cohort, the estimated 3-year, 5-year and 10-year OS rates were 86.95%, 78.91%, and 55.89%, respectively. Meanwhile, the estimated 3-year, 5-year and 10-year CSS rates were 96.71%, 93.73%, and 86.84%, respectively. Multivariate Cox regression analyses demonstrated that increasing age, tumors located in the lower lobe, and stage II were significant predictors of poorer OS while increasing age and tumors located in the bilateral lungs were associated with lower CSS. After PSM analyses, the KM survival curves showed no significant differences in OS or CSS among the four groups., Conclusion: Early-stage MALT-type PPL is indolent in nature. Neither surgery, chemotherapy nor a combination of surgery and chemotherapy can improve OS and CSS, suggesting that "watch and wait" may be a reasonable alternative., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Zhou, Peng, Liang, Cao and Mei.)

Helicobacter pylori infection remains common worldwide and is significantly associated with gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT)lymphoma. This article reviews recent developments in the field of H. pylori with an emphasis on mechanisms of carcinogenesis, and the bacterial, environmental and host factors that may alter risk of developing gastric cancer or gastric MALT lymphoma. The topic of eradication of H. pylori to prevent the development of malignancy and the possibility of a vaccine against H. pylori are also explored. [ABSTRACT FROM AUTHOR]

The article discusses the absence of NOTCH1 gene mutations in MALT lymphomas. It states that NOTCH family of genes encodes a set of four transmembrane receptors that function in cell fate decisions during the development of many cell types, including B-cells, and recent studies have indicated an important oncogenic role for NOTCH activation in various B-cell malignancies.

The optimal treatment strategy and outcome of non-gastric marginal zone lymphoma (MZL) remains undefined. The role of rituximab and fludarabine in MZL has not been critically appraised and compared with conventional chemotherapy. We retrospectively analyzed 81 consecutive patients with non-gastric MZL (mucosa-associated lymphoid tissue lymphoma, n=66; splenic MZL, n=11; nodal MZL, n=4). As a group, the treatment results were favorable, with an overall response rate of 87% and a complete response (CR) rate of 73%. The CR rate was similar for conventional chemotherapy, and rituximab- and fludarabine-containing regimens. However, the relapse rate was significantly decreased in rituximab- and fludarabine-containing regimens. The use of rituximab and fludarabine was associated with acceptable side effects. For splenic MZL, splenectomy was significantly associated with a superior CR rate. Early stage, good performance status, and low international prognostic index risk scores significantly impacted on CR rate and survivals. Rituximab and fludarabine were safe for non-gastric MZL and resulted in more durable remissions. [ABSTRACT FROM AUTHOR]

We have reported the characteristics of magnified endoscopic images of gastric mucosa-associated lymphoid tissue (MALT) lymphoma before and after treatment. In this study, we investigated the diagnostic efficacy of magnified endoscopic images for target biopsy and evaluation of clinical remission. Twenty-one patients diagnosed with localized gastric MALT lymphoma were enrolled. Magnified endoscopy was performed prior to treatment and at a mean period of 1.8 months (1-6 months) after therapy ( Helicobacter pylori eradication in 19 patients and radiation therapy in two patients). Microstructural pattern and abnormal vessels in the lesions were assessed, and corpus mucosa without lymphoma was divided into H. pylori-negative mucosa and H. pylori-positive mucosa. Biopsy was the gold standard in this study. Nonstructural areas with abnormal vessels were observed in all patients before treatment. Fifteen patients achieved pathological complete remission. Disappearance of nonstructural areas and abnormal vessels after therapy was associated with pathological remission. Sensitivities of these findings for diagnosis were 76.9% and 85.7%, respectively, and the specificities were 87.5% and 85.7%, respectively. H. pylori eradication therapy was invalid in three patients with H. pylori-negative mucosa in magnified images. Magnifying endoscopy may be useful for target biopsy of superficial gastric MALT lymphoma in clinical management. [ABSTRACT FROM AUTHOR]

Shacklett BL, Greenblatt RM. Immune responses to HIV in the female reproductive tract, immunologic parallels with the gastrointestinal tract, and research implications. Am J Reprod Immunol 2011; 65: 230-241 The female reproductive tract is a major site of mucosa-associated lymphoid tissue and susceptibility to HIV infection, yet the tissue site(s) of infection and the impact of HIV infection on this important mucosal tissue remain poorly understood. CD4 T cells and other cell types expressing the major coreceptors for HIV, CCR5, and CXCR4 are abundant in both the lower reproductive tract (endocervix and vagina) and the upper tract (endocervix and uterus) and are highly susceptible to infection. Antiviral defenses in the female reproductive tract are mediated by a variety of soluble factors and by mucosal effector cells that differ phenotypically from their counterparts in blood. The immunologic characteristics of the female reproductive tract parallel those of the gut, where major HIV-related immunologic injury occurs. The susceptibility of the female reproductive tract to HIV infection and immunopathogenesis suggests important new avenues for further research. [ABSTRACT FROM AUTHOR]

We retrospectively compared the clinicopathological features of primary intestinal follicular lymphomas (FL-GIs), nodal follicular lymphomas (FL-LNs) and gastrointestinal MALT lymphomas (MALT-GIs), and investigated the distribution and the endoscopic appearances of FL-GI to evaluate the effectiveness of treatment modality. The subjects were 28 FL-GI patients, 135 FL-LN patients and 70 MALT-GI patients. In FL-LNs the clinical stage III-IV was 83%, while in FL-GIs clinical stage I-II was 68%. In MALT-GIs clinical stage I-II was 87%. The overall survival was significantly better in MALT-GI patients than in FL-LN patients. All FL-GI patients were alive at the time of evaluation. Regarding the histological grade (WHO), grade 1 was 81% in FL-GI, whereas in FL-LN grade 2 was 28% and grade 3 was 11%. The Follicular Lymphoma International Prognostic Index was low in 61% of FL-GIs, while in FL-LNs it was equally distributed to low, intermediate and high, suggesting that the prognosis is better in FL-GIs than in FL-LNs. The clinicopathological studies revealed the FL-GI has intermediate characteristics between FL-LN and MALT-GI. We recommend a 'watch-and-wait' policy or chemotherapy with rituximab for the therapy of FL-GIs because the lesions are often located in broader areas from the lower duodenum to the small intestine. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma has been well-described, but rarely do these lesions demonstrate intraocular involvement. We report a case of conjunctival MALT lymphoma with intraocular involvement and novel spectral-domain ocular coherence tomography (SD-OCT) findings. Patient and methods: A 75-year-old woman with biopsy-proven MALT lymphoma of the conjunctiva presented with ipsilateral yellowish diffuse choroidal infiltrates on fundoscopic examination. Choroidal involvement was documented clinically, on ultrasonography, on fluorescein angiography, and by SD-OCT. Treatment consisted of 3 weeks of oral doxycycline and six cycles of systemic chemotherapy with cyclophosphamide, vincristine, prednisone, and rituximab. Results: There was no evidence of progression or recurrence of MALT lymphoma after 9 months of follow-up. Despite complete resolution of clinical findings, ultrasound, and fluorescein angiography, the choroidal lesions remained unchanged on SD-OCT. Discussion: Choroidal involvement of conjunctival MALT is rare, and can be successfully treated. Persistence of irregularities on SD-OCT did not influence management in the presence of clinical improvement and resolution on ultrasonography and fluorescein angiography. [ABSTRACT FROM AUTHOR]

Helicobacter heilmannii induces gastric lymphoid follicles in mice. However, the pathogenic mechanisms behind the induction of gastric lymphoid follicles by H. heilmannii infection have not been elucidated. The aim of this study was to investigate the roles of Peyer's patches (PP) in H. heilmannii-induced immune responses and the development of gastric lymphoid follicles. C57BL/6J and PP deficient mice were infected with H. heilmannii, and in addition to histological and immunohistological examinations, the expression levels of cytokines and chemokines in gastric mucosa were investigated. Gastric lymphoid follicle formation and the infiltration of dendritic cells, B cells, and helper T cells were milder in the PP-deficient mice 1 month after infection, but they were similar in both types of mice after 3 months. The mRNA expression levels of tumor necrosis factor α and CC chemokine ligand 2 were significantly high in the H. heilmannii-infected groups, and CXC chemokine ligand 13 expression was significantly increased in the infected C57BL/6J wild-type mice 1 month after infection. These results suggest that PP are not essential for the formation and development of gastric lymphoid follicles induced by H. heilmannii infection, although they are involved in the speed of gastric lymphoid follicle formation. [ABSTRACT FROM AUTHOR]

The article examines the prognostic factors in patients with marginal zone lymphoma (MZL). The patients in the study were divided into three groups according to the type of MZL such as extranodal, nodal and splenic. The results of the study revealed that splenic MZL patients had the best prognosis among the three groups despite the increased prevalence of negative prognostic indicators. The patients with extranodal and nodal MZL had similar prognosis. The study was able to provide a prognostic scoring system for patients with extranodal MZL.

Background: Cutaneous marginal zone lymphoma (MZL) may be a primary cutaneous condition or the result of secondary involvement from noncutaneous MZL. Distinguishing primary cutaneous MZL (PCMZL) from secondary cutaneous MZL (SCMZL) is of utmost importance for prognostic and therapeutic approach. Objective: We describe the clinical and histologic features of 4 cases of SCMZL (3 cases of nodal MZL and one case of orbital extranodal MZL), compare them with a cohort of 30 cases of PCMZL, and describe distinctive features of SCMZL. Methods: Thirty cases of PCMZL and 4 cases of non-PCMZL with secondary skin involvement were identified in our cutaneous lymphoma and dermatopathology databases. The medical records were reviewed regarding clinical, histologic, laboratory, and radiologic findings; disease course; response to treatment; and follow-up. All cases were reviewed by 3 dermatopathologists. Results: The histopathological and immunohistochemical features of SCMZL were indistinguishable from our cases with PCMZL. However, the clinical presentation in SCMZL appeared to be distinct. We observed these lesions in an older patient population and in 3 of 4 cases the lesions predominantly involved the head/neck area. Limitations: As PCMZL and SCMZLs are exceedingly rare, only 34 patients were identified in this single-institution study. Conclusions: The histologic and immunophenotypic changes in skin lesions from SCMZL may be indistinguishable from those in PCMZL. However, there may be some differences in the typical clinical presentation. PCMZL may be seen in younger patients and favors the trunk and extremities whereas MZL secondarily involving the skin favors the head/neck regions and is limited to older patients. Because there may be considerable overlap in the clinical presentations for patients with primary and secondary cutaneous disease, it is not unreasonable to perform a systemic evaluation for all patients. [Copyright &y& Elsevier]

The article presents a study which examines the role of rituximab and fludarabine in treating extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue (MALT) type. It notes that patients with de novo extranodal MALT lymphoma received 375 mg/m² rituximab and 25 mg/m² fludarabine for four to six cycles. Results show that 62% of the participants achieved a complete remission (CR) while 38% achieved a partial remission (PR) after the third cycle.

The conjunctiva contains organized lymphoid tissue that consists of intraepithelial lymphocytes, subepithelial lymphoid follicles and adjacent lymphatics and blood vessels. This conjunctiva-associated lymphoid tissue (CALT) is assumed to play a key role in the protection of the ocular surface by initiating and regulating immune responses. The article reviews the current knowledge of CALT in humans and compares its structure and functions with mucosa-associated lymphoid tissues at other mucosal sites. An update is given on CALT animal models and on functional studies on the transepithelial transport of microorganisms and antigenic substances by specialized epithelial cells. The use of two-photon microscopy is reviewed regarding its importance to the understanding of dynamic processes going on within CALT. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct clinical pathologic entity that develops in diverse anatomic locations such as the stomach, salivary gland, thyroid, lung, skin and breast. However, colorectal involvement is extremely rare. To our knowledge, only ten cases of primary rectal MALT lymphoma have been reported in the literature. We report a 46-year-old woman with rectal MALT lymphoma, which regressed after radiotherapy. The patient had rectal bleeding. Colonoscopy showed a pseudonodular and ulcerated big fold in the rectum. Microscopic and immunohistologic studies of the biopsy specimen showed typical features of low grade MALT lymphoma. Upper endoscopy showed chronic gastritis with lymphoid follicles but without any infiltration of lymphoma cells. Helicobacter pylori infection was confirmed by histology. No extra-intestinal involvement was found on the staging evaluation, which included computed tomography (CT) of the abdomen, chest, pelvis and a bone marrow biopsy. We attempted to eradicate H. pylori with a 7-day course of omeprazole, amoxycillin, and metronidazole. Eradication was proved successful by endoscopy. Repeated colonoscopy 4months after the end of treatment showed that the rectal tumor had not regressed. Biopsy specimens confirmed the persistent infiltration of lymphoma cells. The patient was considered to be a non-responder to eradication therapy and was indicated for radiotherapy. He underwent a total of 34Gy. Complete regression was confirmed by colonoscopic and histologic examination at 2months after the end of treatment. He was followed up closely with colonoscopy, but no relapse of these lesions was detected after 12 months. [Copyright &y& Elsevier]

Extranodal marginal zone lymphoma is a low-grade B cell lymphoma that presents with an indolent clinicopathologic nature. Although this tumor can occur in various sites, including the gastrointestinal tract and lungs, it develops and spreads extremely rarely along the trachea and central airway. We report a case of extranodal lymphoma of mucosa-associated lymphoid tissue with tracheobronchial involvement. An 83-year-old woman presented with a cough and dyspnea. Bronchoscopic evaluation confirmed diffuse, multiple nodular lesions in both the trachea and large bronchi, and she was diagnosed with an extranodal marginal zone lymphoma of the tracheobronchial tree. After systemic chemotherapy, she survived for more than 18 months. [ABSTRACT FROM AUTHOR]

Summary: Nongastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma, although generally indolent in nature, has variable and heterogeneous clinical course and biologic behavior. We have evaluated the clinical features and follow-up of patients with MALT lymphomas involving the head and neck in our institution. Forty-four new patients with MALT lymphomas arising in ocular adnexa (24 patients, group A) and other head and neck sites (20 patients, group B) of the salivary gland (13), thyroid gland (3) and other regions (4) were retrospectively analyzed. At initial diagnosis, 21 patients had solitary lesions (16/24 in the group A vs. 5/20 in the group B, P =.008); 23 had disseminated disease at multiple sites (11 patients) and/or lymph node involvement (15 patients: 3/24 in the group A vs. 12/20 in the group B, P =.025). Treatment consisted of local therapy, consisting of surgical resection and/or radiotherapy, in 34 patients and systemic chemotherapy with/without local therapy in 10 patients. Eight patients experienced tumor recurrence: four patients died of disease, two were alive with disease, and two were disease-free at last follow-up. With a mean follow-up of 46 months, the 5-year overall survival and relapse-free rates were 83% and 74%, respectively, which did not differ between the two groups (P >.5). Patients with MALT lymphomas of the head and neck are at relatively high risk for multifocal or lymph node involvement. Recurrence at prolonged times after therapy indicates the need for close long-term monitoring, and for prospective trials to prevent recurrence. [Copyright &y& Elsevier]

Purpose: Primary dural lymphoma is a rare intracranial lymphoma that almost always has a marginal zone histologic type and immunophenotype and often remains localized and is thus potentially curable with radiotherapy (RT) alone. The unusual location and histologic type of primary dural marginal zone lymphoma (PDMZL) distinguish it from primary central nervous system lymphoma and poses treatment dilemmas of technique, volume, and dose that have not been well addressed. We set out to analyze our recent experience in treating PDMZL and reviewed the limited published data available. Methods and Materials: Between 2002 and 2006, we treated 5 patients with localized PDMZL. Of these 5 patients, 3 had unilateral and 2 had bilateral/multifocal involvement, and 3 underwent subtotal tumor resection and 2 biopsy only. Whole brain RT was given before involved-field RT (IFRT) in 4 patients and 1 received IFRT alone. The median whole brain RT, IFRT, and total RT dose was 20, 12, and 30 Gy, respectively. The planning computed tomography scan was always fused with the post-gadolinium magnetic resonance imaging scan to assist in the IFRT volume determination. We also analyzed the published data from 27 additional patients. Results: The median follow-up was 34 months (range, 31–52). All obtained lasting local control. One patient developed a relapse in the soft tissue of the flank and additional systemic progression but no central nervous system recurrence. At last follow-up, no significant treatment-related neurotoxicity was detected. Conclusion: The results of our study have demonstrated that a combination of whole brain RT/IFRT or even low-dose IFRT alone provides excellent durable local control of PDMZL. This approach is potentially curative, possibly without significant neurotoxicity. Additional study and longer follow-up are needed to determine the appropriate RT dose and volume parameters for this rare, debilitating, and yet potentially curable lymphoma. [Copyright &y& Elsevier]

Mucosal vaccination offers attractive advantages to conventional systemic vaccination, such as higher levels of antibodies and protection at the airway surface. This review gives an overview of recent experimental and clinical data on nasal, oral and sublingual vaccines against bacterial respiratory pathogens, such as Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Moraxella catarrhalis, Bordetella pertussis, Pseudomonas aeruginosa and Mycobacterium tuberculosis. Subsequently, we discuss further vaccine development that opens the focus to clinical use. [ABSTRACT FROM AUTHOR]

The follicle-associated epithelium (FAE) overlying the follicles of mucosa-associated lymphoid tissue is a key player in the initiation of mucosal immune responses. We recently reported strong clusterin expression in the FAE of murine Peyer’s patches. In this study, we examined the expression of clusterin in the human gut-associated lymphoid tissue (GALT) and Waldeyer’s ring. Immunohistochemistry for clusterin in human Peyer’s patches, appendix and colon lymphoid follicles revealed expression in M cells and in follicular dendritic cells (FDCs). Using cryo-immunogold electron microscopy in Peyer’s patches, we observed cytosolic immunoreactivity in M cells and labeling in the ER/Golgi biosynthetic pathway in FDCs. In palatine tonsils and adenoids, we demonstrated clusterin expression in germinal centers and in the lymphoepithelium in the crypts where M cells are localized. In conclusion, clusterin is expressed in M cells and follicular dendritic cells at inductive sites of human mucosa-associated lymphoid tissue suggesting a role for this protein in innate immune responses. Moreover, the use of clusterin as a human M cell marker could prove to be a valuable tool in future M cell research. [ABSTRACT FROM AUTHOR]

Aims: To determine the immunophenotype of gastric and intestinal diffuse large B-cell lymphomas and investigate the clinical significance of patterns of antigen expression. Methods and results: Immunohistochemistry was performed for detection of CD10, Bcl-6, Bcl-2, MUM1 and p53 in paraffin-embedded tissue from 29 patients with primary diffuse large B-cell lymphoma of the stomach and intestine. Statistical analysis was performed using χ2 and Fisher’s exact tests. Survival data were analysed by the Kaplan–Meier method and compared using a log rank test. Thirteen of the 29 cases were of germinal centre phenotype (CD10+ or CD10–, Bcl-6+ and MUM1–). Sixteen were of activated B-cell phenotype (all CD10– and either Bcl-6–, or Bcl-6+ and MUM1+). Sixteen cases showed Bcl-2 expression. There was a statistically significant difference ( P < 0.05) in immunophenotype of the neoplastic cells relating to tumour site. Of 15 gastric lymphomas, 11 were of activated B-cell phenotype and 9/14 intestinal tumours were of germinal centre phenotype. No significant survival difference was found between groups with regard to expression of any of the antigens investigated. Conclusions: Primary gastric and intestinal large cell lymphomas appear to show different patterns of antigen expression. This suggests that these tumours arise by different mechanisms and/or from different causes. Gastric diffuse large B-cell lymphomas are usually of activated B-cell phenotype that may reflect a relationship with low-grade gastric lymphomas of marginal zone type. Intestinal diffuse large B-cell lymphomas usually show a germinal centre phenotype, suggesting an origin from germinal centre B cells. In this study the tumour immunophenotype was not associated with any difference in survival. [ABSTRACT FROM AUTHOR]

Abstract: Lymphoid organs are generally classified in a hierarchy with primary lymphoid organs such as the thymus and bone marrow for the production of receptor specific T and B lymphocytes, respectively, independent of antigens. In secondary lymphoid organs such as lymph nodes, spleen, and tonsils, the lymphocytes are expanded due to antigen exposure, producing memory T cells and effector B cells, resulting in plasma cells. Tertiary lymphoid tissues are often defined as aggregations of lymphoid cells in autoimmune diseases. It will be outlined that all these organs have a high plasticity and also the thymic medulla is included in the route of migrating mature T cells and the bone marrow, not only in the traffic of CD4+ but also of CD8+ lymphocytes. The mucosa-associated lymphoid organs depend to a much larger extent on microbial antigen and are much more diverse than often described. The role of structural elements as well as blood and lymphatic vessels as an entry and exit site of lymphocytes will be outlined. Using a precise terminology, taking account of the plasticity of these organs at different ages and considering species differences will reduce misunderstandings among immunologists. [Copyright &y& Elsevier]

Objectives: Extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) accounts for about 7% to 8% of all B-cell lymphomas and 50% of all gastric lymphomas. Long-term localized growth is typical of MALT lymphoma. Multifocal manifestations are possible in advanced stages. MALT lymphoma of the larynx is a very rare disease; only 15 cases have been reported in the literature. Methods: We report a case of multifocal MALT lymphoma affecting the larynx associated with extraesophageal reflux, chronic laryngitis, and gastric Helicobacter pylori infection. The staging revealed a recurrent tumor of MALT lymphoma in the stomach and an involvement of the right conjunctiva. Results: Following recent reports on successful treatment of MALT lymphoma with antibiotics, initial empirical therapy with doxycycline calcium led to a subjective clinical symptom improvement but no objective response as assessed by laryngoscopy, magnetic resonance imaging of the larynx, and esophagogastroduodenal endoscopy. Because of the advanced stage and multiple extranodal manifestations of the MALT lymphoma, the patient received 3 cycles of chemoimmunotherapy according to the FCR protocol (fludarabine phosphate-cyclophosphamide-rituximab). No evidence of disease was observed after a 6-month follow-up. Conclusions: In the rare diagnosis of MALT lymphoma of the larynx, comprehensive staging is indispensable to exclude multifocal involvement. In contrast to the treatment of primarily localized MALT lymphoma, multifocal disease warrants systemic therapy. [ABSTRACT FROM AUTHOR]

Two major antibody classes operate in saliva: secretory IgA (SIgA) and IgG. The former is synthesized as dimeric IgA by plasma cells (PCs) in salivary glands and is exported by the polymeric Ig receptor (pIgR). Most IgG in saliva is derived from serum (mainly via gingival crevices), although some is locally produced. Gut-associated lymphoid tissue (GALT) and nasopharynx-associated lymphoid tissue (NALT) do not contribute equally to mucosal PCs throughout the body. Thus, enteric immunostimulation is an inadequate mode of stimulating salivary IgA antibodies, which are poorly associated with the intestinal SIgA response, for instance after enteric cholera vaccination. Nevertheless, the IgA response in submandibular/sublingual glands is better related to B cell induction in GALT than the parotid response. Such disparity is suggested by the elevated levels of IgA in submandibular secretions of AIDS patients, paralleling their highly upregulated intestinal IgA system. Moreover, in patients with active celiac disease, IgA antibodies to disease-precipitating gliadin are reliably represented in whole saliva but not in parotid secretion. Parotid SIgA may be more consistently linked to immune induction in palatine tonsils and adenoids (human NALT), as supported by the homing molecule profile of NALT-derived B cell blasts. Also several other variables influence the levels of antibodies in oral secretions. These include difficulties with reproducibility and standardization of immunoassays, the impact of flow rate, acute or chronic stress, protein loss during sample handling, and uncontrolled admixture of serum-derived IgG and monomeric IgA. Despite such problems, saliva remains an interesting biological fluid with great scientific and clinical potentials. [ABSTRACT FROM AUTHOR]

Background: We evaluated the efficacy and toxicity of radiotherapy (RT) in patients with low-grade gastric marginal zone lymphoma. Methods: A retrospective review of consecutive cases of gastric marginal zone lymphoma treated by radical RT at the Peter MacCallum Cancer Centre and Radiation Oncology Victoria between January 1980 and September 2003 was carried out. Results: Eighteen patients (11 men and 7 women) were identified. The median age at commencement of RT was 65 years (range 42–84 years). Prior treatment included Helicobacter pylori eradication in 12 patients, chemotherapy in 7 and surgery in 2, whereas 2 patients had no prior therapy. The median time to progression after commencement of last treatment before RT was 4.8 months (range 0–129.4 months). The radiation fields included the stomach plus perigastric and coeliac nodes in 15 patients (83%), stomach plus spleen in 2 patients (11%) and stomach plus para-aortic nodes in 1 patient (6%). The median RT dose was 30 Gy (range 30–36 Gy) in a median 20 fractions (range 17–24 fractions). One patient required treatment interruption for acute toxicity. A complete response on post-RT biopsies was achieved in 17 of 18 patients (94%). With a median follow up of 4.5 years after RT, 3 of these 17 patients (18%) have had a recurrence. At the last follow up, 11 patients were alive in continuous complete histological remission. No late renal toxicity was identified. Conclusion: Radiotherapy is an effective, well-tolerated treatment for patients with low-grade gastric marginal zone lymphoma, including those who have had prior therapy. [ABSTRACT FROM AUTHOR]

Summary: Background: Primary Sjögren''s syndrome (pSs) is an autoimmune rheumatic disease that may express in a small number of patients a spectrum of lymphoproliferative diseases. The aim of this study was to describe clinical, imaging and pathology features of the extranodal marginal zone B-cell lymphoma (MZCL) of the lung of mucosa-associated lymphoid tissue (MALT) type in patients with pSs. Methods: All patients () with biopsy proven MZCL of the lung of MALT type diagnosed in a tertiary teaching hospital during the last 7 years were studied. Results: Seven patients had pSs. Almost all patients presented an indolent clinical course, contrasting strongly with the spectacular radiological findings in both chest roentgenograms and computed tomography. Pathology infiltration patterns observed were either nodular, peribronchial–perivascular, alveolar, or interstitial. Immunohistochemical study in all cases showed B cell phenotypes. Immunoglobulin light chain restriction was demonstrated in all patients. Monoclonal IgM(κ) was evident in 5/7, IgM(λ) in 1/7 and IgG (κ) in 1/7 of patients. Conclusions: Lung MZCL associated with pSs are characterized by an important dissociation between clinical expression and radiological pattern. Clinical presentation and imaging features are not specific. Therefore, histologic documentation is mandatory to ensure diagnosis. Various chemotherapeutic agents in combination with rituximab lead to partial or complete remission in the majority of patients. [Copyright &y& Elsevier]

The concept of mucosa-associated lymphoid tissue (MALT) lymphomas was introduced by Isaacson and Wright [Cancer 1983;52:1410-1416] in 1983. After more than 20 years of clinical research MALT lymphomas are now recognized as a distinct subtype of non-Hodgkin's lymphoma (NHL) with unique pathogenic, histological, and clinical features. Although this subtype of NHL occurs frequently, optimal management remains elusive. This manuscript reviews features of the clinical presentation, diagnosis, pathology, molecular characteristics, and management of both gastric and non-gastric MALT lymphoma. [ABSTRACT FROM AUTHOR]

Marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue type is a peculiar variant of B-cell neoplasm showing distinct clinical and pathologic features. Its occurrence in children or adolescents is extremely uncommon. We describe the case of an 11-year-old boy who developed such a lymphomatous process involving primarily the skin. The tumor was characterized by a maturing plasma cell population that included immunoblasts, heavy-chain but not light-chain restriction suggestive of monoclonality, and a prevalent, focally granulomatous component of histiocytes. As an additional interesting feature, a trisomy 3 was demonstrated by fluorescence in situ hybridization analysis. The clinical, morphological, phenotypic, and genetic characteristics seen in our patient do not differ significantly from those described in primary cutaneous MZBCL occurring in adults. [ABSTRACT FROM AUTHOR]

To evaluate the sensitivity of 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in patients with mucosa-associated lymphoid tissue (MALT) lymphoma. A total of 32 patients with a histological diagnosis of extra-nodal MALT lymphoma were referred to the PET Centers in the last 2 years (2003 – 2004) and scanned with 18F-FDG-PET following standard procedures. Overall, the results of 50 18F-FDG-PET scans performed in either active disease state or in complete remission were reviewed. Sites of primary disease included stomach, lung, parotid, skin, orbit, mandible, esophagus and uterus. This study retrospectively enrolled 26 patients with known active disease. 18F-FDG-PET was true positive (TP) in 21/26 patients and false negative (FN) in 5/26. Sensitivity of 18F FDG-PET for extra-nodal MALT was 81%. The data show that 18FDG-PET is a useful diagnostic tool in order to stage, restage or monitor disease in patients with extra-nodal MALT lymphoma. [ABSTRACT FROM AUTHOR]

Prospective studies have reported ongoing remissions in most patients with localized Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue lymphoma after curing the infection. Using specific selection criteria, the outcome of 196 patients treated in routine clinical practice was analysed. Complete remission rates, stability of remissions and frequency of relapse and histologic residual disease were in accordance with previous prospective clinical trials, whereas the median age was higher. Only a minority had a complete staging, and it may be expected that there is a significant group of patients with an unrecognized higher stage in this cohort. The frequency of follow-up investigations was also not considered as recommended in a considerable number of patients. Nevertheless, the outcome of patients was favourable regardless of limited staging and follow-up procedures. Amended recommendations and special guidelines for elderly and patients with concomitant disease should be considered. [ABSTRACT FROM AUTHOR]

Abstract: B-cell clonality, assessed by PCR for amplification of the VDJ region of the immunoglobulin heavy chain gene (IgH), is used to support the diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). It has also been described in simple gastritis cases, without any histological hint for lymphoma, especially in the presence of lymphoid follicles. We analyzed a randomly selected series of 130 gastric biopsies with histologically described lymphoid follicle formation and investigated these for the prevalence of B-cell clonality using different PCR-based methods to discuss its usefulness in the differential diagnosis of GML. A seminested PCR for the IgH gene was performed and evaluated by agarose gel electrophoresis, GeneScan technique, and melting-curve analysis. The majority of cases revealed histologically chronic active Helicobacter pylori gastritis. Monoclonality was detected in 7.5% (10 of 130) and 7% (9 of 130) of samples using GeneScan technique and melting-curve analysis, respectively. In eight of eight samples investigated, monoclonality was not demonstrated in deeper sections of the same biopsy using GeneScan technique, favoring the diagnosis of a reactive process rather than overt lymphoma. Electrophoresis proved more difficult to interpret and revealed clonal cases in 14% (18 of 130). We conclude that GeneScan technique and melting curve analysis are the methods of choice for clonality analysis in gastric biopsies. Analyses of different deep sections with advanced PCR technology might be the method of choice for future analyses. In our opinion, the question of whether detected monoclonality can be interpreted as malignant lymphoma is still open. [Copyright &y& Elsevier]

An 82-year-old woman with monoclonal immunoglobulin (Ig) M-type paraproteinemia had a large opacity in the right lung field. The abnormal shadow on roentgenogram had persisted for more than 6 years since the initial diagnosis of paraproteinemia, which had been diagnosed as Waldenström’s macroglobulinemia (WM). Computed tomography revealed the lesion as a pulmonary tumor which was finally diagnosed as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) after surgical removal. MALT lymphoma constitutes the majority of primary pulmonary lymphomas and is often associated with monoclonal IgM-type paraproteinemia as well as WM, a distinctive lymphoproliferative disorder. Pulmonary MALT lymphoma should frequently be suspected in case of an indeterminate pulmonary tumor with IgM-type paraproteinemia. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of the study was to evaluate the usefulness of 18F-FDG-PET in patients with gastric lymphoma, in particular those affected by mucosa-associated lymphoid tissue (MALT) type and aggressive gastric non-Hodgkin's lymphoma (NHL). MATERIAL AND METHODS: The study group consists of 15 patients with a previous diagnosis of gastric NHL referred to our PET centres in Bologna Hospital and Rovigo Hospital, Italy, in the period 2003-2004. In 9/15 patients the subsequent histological evaluation was consistent with a gastric MALT lymphoma, while aggressive gastric NHL was diagnosed in the other 6/15. PET scan was carried out in patients with known active disease in order to stage or re-stage disease prior to treatment or in patients in complete clinical remission to monitor disease during follow up. Patients were considered in complete clinical remission if free from disease for at least 8 months after chemotherapy or surgery. 18F-FDG PET was performed following standard procedures. RESULTS: Overall 18F-FDG-PET was true positive in all cases of gastric MALT and non-MALT aggressive NHL with known active disease, while no pathological 18F-FDG uptake was evident in the subjects who were in complete clinical remission. The degree of 18F-FDG uptake (mean SUVmax values) in MALT lymphoma was much less intense in comparison to aggressive gastric NHL, suggesting a prognostic role of SUV calculation in gastric lymphomas. CONCLUSION: Our data demonstrate the significant accuracy of 18F-FDG-PET in detecting active disease in gastric lymphoma of both MALT and non-MALT NHL type. A higher SUV value appears to be related to a more aggressive disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To establish a sequential diagnostic procedure of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and provide evidence for selected optimal cases to be treated in the early stage. METHODS: Thirty-one cases of gastric lymphoid hyperplasia (GLH) were selected and multiple investigations including histology, protein level, DNA and chromosome levels, combined with clinical follow-up were performed. Histological grade was according to Isaacson's criteria of GLH; CD20, UCHL-1 (CD45RO), anti-kappa (κ), anti-lambda (λ) and Ki-67 were used for immunohistochemical staining; semi-nested polymerase chain reaction (PCR) was used to detect IgH gene rearrangement and reverse-transcription PCR (RT-PCR) was used to detect API2-MALT1 fusion of the chromosome translocation t(11;18)(q21;q21). Twenty-nine cases underwent eradication therapy for Helicobacter pylori. Changes in histological grade, endoscopic appearance, expression of Ki-67 and IgH gene rearrangement were compared after eradication treatment. RESULTS: Of the 31 cases of GLH with predominant chronic gastritis and gastric ulcer most were histological grade 2 and 3. Only one case had λ light chain restriction and 10 cases had monoclonal IgH gene rearrangement. Expression of Ki-67 and monoclonal IgH gene rearrangement were significantly increased with increased lymphoid hyperplasia ( P < 0.05). Two cases had API2-MALT1 fusion. Helicobacter pylori was eradicated in 25 cases and another course of treatment had to be given in 4 cases. All cases were followed up for 1.5–37 months. Of the 27 successful eradication cases, 18 showed complete regression both histologically and endoscopically, 4 had partial regression and 7 were unchanged. CONCLUSIONS: A sequential diagnostic procedure based on histology, expression of Ki-67 combined with clonality of IgH rearrangement and API2-MALT1 fusion helps to diagnosis of early stage gastric MALT lymphoma and choose the best treatment strategy. [ABSTRACT FROM AUTHOR]