Cell Lymphoma Of Mucosa-associated Lymphoid Tissue Research Articles

Synchronous pulmonary MALT lymphoma and squamous cell lung cancer: a case report

Pulmonary B-cell lymphoma in the extranodal marginal zone of mucosa-associated lymphoid tissue (MALT), a rare tumor originating from bronchial mucosa-associated lymphoid tissue, is the major histologic type of primary pulmonary lymphoma. Combined lung squamous cell carcinoma with pulmonary MALT lymphoma is rare. A 63-year-old male patient presented to the hospital because of a dry cough, and chest CT showed soft tissue density nodules in the upper lobe of the right lung, the boundary was visible lobulation and spiculation, and the middle lobe of the right lung showed patchy shadow, moderate enhancement, associated with bronchial traction. After a multidisciplinary diagnosis and treatment (MDT) discussion, surgical resection was done for the patient, and postoperative pathological results showed pulmonary MALT lymphoma combined with lung squamous carcinoma. For complex pulmonary multiple lesions, judgment needs to be made after MDT discussion, and timely intervention is required for lesions suspicious of malignancy. There are no uniform recommendations for the management of mixed tumors of the lung, and an individualized treatment plan needs to be developed based on the patient’s actual condition.

The Spectrum of Helicobacter-Mediated Diseases.

Helicobacter pylori is the leading cause of peptic ulcer disease. The infection has been implicated in more than 75% of duodenal ulcer cases and 17% of gastric ulcer cases. H. pylori has been classified as a human carcinogen, since it is the main cause of distal gastric adenocarcinoma and B cell mucosa-associated lymphoid tissue lymphoma. Evidence also links H. pylori with extragastric conditions including iron deficiency anemia, idiopathic thrombocytopenic purpura, and vitamin B12 deficiency. Studies indicate that H. pylori may be protective against other conditions of the gastrointestinal tract (e.g., reflux esophagitis and related pathologies) and elsewhere in the body (e.g., asthma). The infection is asymptomatic in the vast majority of cases; more serious outcomes occur in only 10-15% of infected individuals. Despite extensive research over the past 3 decades, there is no effective vaccine, and the circumstances leading to disease development remain unclear. In addition, there is now a growing prevalence of antimicrobial resistance in H. pylori. This review discusses these important issues.

Immunomodulatory treatment for mucosa‐associated lymphoid tissue lymphoma (MALT lymphoma)

The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma has been characterized as a dynamic process driven by lymphoma cell dependency on T-cell signaling, chronic antigenic stimulation of marginal zone B-cells and activation of the nuclear factor-kappa B signaling pathway. This concept is underlined by the strong causal connection of chronic Helicobacter pylori associated gastritis and MALT lymphoma development based on perpetual auto-antigenic stimulation of Helicobacter pylori-specific T-cells, but also its association with further potential infectious triggers and autoimmune disorders for extragastric lymphoma sites. Thus, given the dependency of MALT lymphoma cells on the tumor microenvironment, this specific entity appears highly suitable for immunomodulatory treatment strategies. Several approaches have been assessed in the last years including promising data on immunomodulatory agents "IMiDs" thalidomide and lenalidomide, macrolide antibiotics and antibodies. The aim of the present review is to discuss rationales for immunomodulatory therapies in MALT lymphoma and to present the statu quo on immunomodulatory and therefore chemotherapy-free treatment strategies for these patients.

PTEN Loss and Cyclin A2 Upregulation Define a PI3K/AKT Pathway Activation in Helicobacter pylori-induced MALT and DLBCL Gastric Lymphoma With Features of MALT.

Helicobacter pylori infection is strongly associated with primary gastric diseases, such as extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, diffuse large B-cell lymphoma (DLBCL) with histologic evidence of MALT origin, and gastric carcinoma. The cytotoxin-associated gene A (CagA) protein behaves as a bacterial oncoprotein, promoting tumorigenesis via dysregulation of the phosphatidylinositol 3-kinase/AKT pathway (PI3K/AKT). We investigated the molecular mechanisms of PI3K/AKT pathway dysregulation in H. pylori-induced MALT and DLBCL gastric lymphoma. Immunohistochemical assays for CagA, phospho(p)-S473-AKT, PTEN, SHIP, and cyclin A2 proteins were performed on samples from 23 patients with H. pylori-positive MALT lymphoma and 16 patients with H. pylori-positive gastric DLBCL. We showed that CagA localization is correlated with the activation of the AKT pathway in both MALT and DLBCL lymphoma cells. Interestingly, we found a close association between the loss of PTEN, the overexpression of cyclin A2, and the phosphorylation of AKT in gastric MALT and DLBCL tumor cells.

1984 Helicobacter pylori-Negative MALT Lymphoma Presenting as Massive Recurrent Gastrointestinal Hemorrhage

INTRODUCTION: Extranodal marginal zone lymphoma or low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT), an uncommon type of non-Hodgkin lymphoma (NHL), accounts for 5–10% of NHL in the US (18.3 cases per 1 million person-years1). It usually presents as gastro-esophageal reflux, nausea, anorexia, weight loss or occult GI bleeding2. Massive GI bleeding is unusual and rare. CASE DESCRIPTION/METHODS: Here we present a 68-year-old woman who presented with weakness and syncope after large volume hematemesis. Physical exam showed tachycardia, hypotension and conjunctival pallor. Her hemoglobin and hematocrit on admission were 8.5 g/dL and 25.6 %. She was managed with IV fluids, packed RBC transfusion and Pantoprazole and Octreotide infusions. An EGD within 24 hours showed erythematous, friable, spontaneously oozing mucosa with neovascularization in gastric fundus which was treated with bipolar cautery. A biopsy was not obtained due to recent bleeding. She was discharged on oral Pantoprazole. Two days later she was readmitted due to severe recurrent hematemesis with similar findings on repeat EGD. Bleeding was controlled with APC and biopsies were obtained from the gastric fundus. Due to the recurrent bleeding, an angiogram was performed. Active bleeding could not be seen. Prophylactically, left gastric artery was embolized. Biopsies revealed low-grade B cell MALT lymphoma with negative H.pylori. She was treated with 20 fractions of radiotherapy with the intention to cure. She did not experience further episodes of bleeding and has remained in remission since. DISCUSSION: Studies show the indolent nature of GI MALT lymphoma3, but our case illustrates the life-threatening presentation of a rare low-grade B cell MALT lymphoma as massive and recurrent hematemesis with negative underlying H.pylori infection or autoimmune process45. H.pylori positive localized MALT lymphoma is treated with the eradication of infection. H pylori negative, localized and recurrent disease is treated with radiotherapy6. Chemotherapy and/or immunotherapy is given when patients fail to respond to radiotherapy or develop metastasis. Long term endoscopic and laboratory follow up is needed as gastric MALT lymphoma is associated with a significant risk of gastric adenocarcinoma8 and increased incidence of gastric cancer and residual NHL. Our case emphasizes the importance of early diagnosis and timely intensive radiotherapy of a localized but aggressive gastric MALT lymphoma which induced remission and cessation of GI bleeding.

A Case of Orbital MALT Lymphoma in a Patient with Rheumatoid Arthritis

Purpose: To report a case of orbital mucosa-associated lymphoid tissue (MALT) lymphoma that occurred in a patient with rheumatoid arthritis (RA). Case summary: A 70-year-old male with alleged RA presented with a 3-month history of spontaneous and painless upper and lower eyelid swelling in the right eye. On initial examination, palpable nodules were observed at the right upper and lower eyelids and orbital computed tomography (CT) revealed a contrast-enhancing nodule just inferior to the lacrimal gland, thus an incisional biopsy was performed. The pathological report showed malignant orbital lymphoma (low grade extranodal marginal zone B cell lymphoma of MALT). Since distant metastases were not detected on whole-body CT and positron emission tomography, the patient was advised to keep previous medication and regular follow-up examinations. Conclusions: The possibility of MALT lymphoma should be considered as a differential diagnosis in patients with eyelid swelling and autoimmune diseases such as RA. J Korean Ophthalmol Soc 2015;56(5):780-783

Helicobacter pylori infection: new pathogenetic and clinical aspects.

Helicobacter pylori (H. pylori) infects more than half of the world's human population, but only 1% to 3% of infected people consequently develop gastric adenocarcinomas. The clinical outcome of the infection is determined by host genetic predisposition, bacterial virulence factors, and environmental factors. The association between H. pylori infection and chronic active gastritis, peptic ulcer disease, gastric cell carcinoma, and B cell mucosa-associated lymphoid tissue lymphoma has been well established. With the exception of unexplained iron deficiency anemia and idiopathic thrombocytopenic purpura, H. pylori infection has no proven role in extraintestinal diseases. On the other hand, there is data showing that H. pylori infection could be beneficial for some human diseases. The unpredictability of the long-term consequences of H. pylori infection and the economic challenge in eradicating it is why identification of high-risk individuals is crucial.

BCL10 aberations and NF-kappa B activation involving p65 are absent or rare in primary gastric MALT lymphoma.

Mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 5-17% non-Hodgkin lymphomas (NHL). The molecular pathogenesis of MALT lymphomas is not well-established. The aim of this study was to evaluate immunohistochemically determined nuclear coexpression of BCL10 and NF-kappaB (NF-kappaB) in tumor cells of gastric MALT lymphoma and its impact on the patogenesis and outcome of the disease. Medical records of 35 patients with newly diagnosed gastric MALT lymphoma were analyzed and biopsy specimens were immunostained for BCL10 and NF-kappaB expression (p65 subunit). The median age of 35 patients diagnosed with gastric MALT lymphoma was 63.5 years (male/female = 21/14). Symptoms were present in 23/35 (65.7%) patients with the weight loss as the most common symptom. Gastric MALT lymphomas were usually localized in the stomach corpus and corpus and antrum (45.7% and 31.2%, respectively). H. pylon infection was confirmed in 20 out of 30 (66.7%) patients. Treatment options were as follows: immunochemotherapy in 10 (28.5%) patients, surgery in 9 (25.8%) patients, combined surgery and chemotherapy in 14 (40%) patients and supportive measures in 2 (5.7%) patients. Complete remission was achieved in 13 (37.10/) patients and partial remission in two (5.7%/) patients. Sixteen (45.7%/) patients had disease progression (p < 0.001). Cytoplasmatic expression of BCL10 in tumor cells was detected in 19 (54.3%) specimens. Nuclear expression was detected in no specimen. Cytoplasmic expression of NF-kappaB was present in 22 (65.7%) specimens, but nuclear expression was not detected in any specimens. Nuclear expressions (activation)of NF-kappaB p65 subunit and BCL10 were not detected in specimens of gastric MALT lymphoma. The correlation of nuclear coexpression of BCL10 and NF-kappaB in gastric MALT lymphoma was not established. These results indicate that other mechanisms and signal pathways are active in lymphogenesis of gastric MALT lymphoma, as that apoptotic inhibition is not the main, nor the only mechanism in tumorogenesis.

Endocytoscopic findings of lymphomas of the stomach.

BackgroundThe gastric lesions of various lymphomas were observed at the cellular level using endocytoscopy.MethodsEndocytoscopy and magnifying endoscopy with narrow band imaging (NBI) were performed in 17 patients with lymphomas of the stomach. The lesions consisted of 7 with low-grade mucosa-associated lymphoid tissue (MALT), 5 with gastric involvement by adult T-cell leukemia/lymphoma (ATLL), 4 with diffuse large B-cell lymphoma (DLBCL), and 1 with peripheral T-cell lymphoma.ResultsOn conventional endoscopy, 9 were classified as having superficial spreading type, 7 were mass-forming type, and 1 was diffuse infiltrating type. Anti-H. pylori treatment was given in the 7 MALT lymphoma cases. NBI magnification endoscopy invariably showed dilatation or ballooning and destruction of gastric pits and elongation and distortion in microvessels. Endocytoscopy showed mucosal aggregation of interstitial cellular elements in almost all gastric lymphoma cases. The nuclear diversity in size and configuration was exclusively seen in gastric lymphomas other than MALT lymphoma, whereas the nuclei of MALT lymphoma cells were regular and small to moderate in size. Inter-glandular infiltration by lymphomatous cell elements was frequently observed in MALT lymphoma and DLBCL, but it was uncommon in peripheral gastric T-cell malignancies. Endocytoscopy could identify the disease-specific histology, the lymphoepithelial origin, as inter-glandular infiltration of cellular components in MALT lymphoma and the possibly related DLBCL cases. Complete regression (CR) was observed in 2 of the 7 MALT lymphoma patients. In the 2 patients with CR who underwent repeat endocytoscopy, the ultra-high magnification abnormalities returned to normal, while they were unchanged in those without tumor regression.ConclusionsOn endocytoscopy, intra-glandular aggregation of cellular components was invariably identified in lymphomas of the stomach. Nuclear regularity in size and configuration may indicate the cytological grade, differentiating the indolent low-grade from aggressive lymphoproliferative diseases. The inter-glandular infiltration seen on endocytoscopy can indicate the lymphoepithelial lesions seen in MALT lymphoma and related DLBCL. Endocytoscopy would be applicable for virtual histopathological diagnosis of different lymphoproliferative disorders and their clinical assessment during ongoing endoscopy.

Malt Lymphoma of the Colon: a Rare Occurrence

Non-Hodgkin's lymphoma (NHL) is one of the leading causes of cancer in the US. NHL can be seen in the gastrointestinal tract in extralymphatic presentation. Primary GI lymphomas are rare. When present, they are more common in the stomach and small bowel. The most common histologic subtype affecting the gastrointestinal tract and colon is diffuse large B cell lymphoma. These are generally aggressive and are composed of rapidly proliferating cells of B cell origin. The second most common colorectal lymphoma is mucosa-associated lymphoid tissue (MALT)-associated low-grade B cell lymphoma. MALT-associated lymphomas are low-grade tumors arising from B cells associated with mucosal immunity. MALT is predominantly found in the gastrointestinal tract and plays a vital role in immune surveillance, mucosal regeneration, and in carcinogenesis. In the colon, lymphoid tissue consists of isolated lymphoid follicles which are composed mainly of B lymphocytes. These cells occasionally undergo abnormal proliferation and give rise to lymphoma of the MALT type. Colonic MALT lymphoma is a rare entity of increasing recognition, for which no definitive treatment has been established. There are very few case reports of colonic MALT type lymphoma given its uncommon occurrence, thereby lacking sufficient data required in evaluation, management, and treatment of these patients. We describe a rare case of colon marginal-zone B cell lymphoma of MALT (MALT lymphoma) found on routine colonoscopy. Case Presentation

Detection of the Helicobacter pylori CagA protein in gastric mucosa-associated lymphoid tissue lymphoma cells: clinical and biological significance

We previously reported that CagA can be translocated into B cells in Helicobacter pylori (HP) coculture media, and the translocation appears biologically significant as activation of the relevant cellular pathways was noticed. In this study, we further explore if CagA can be detected in malignant B cells of HP-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Expression of CagA was evaluated by immunohistochemistry. CagA expression was further confirmed by western blot analysis. The association between CagA expression in malignant B cells and tumor response to HP eradication therapy (HPE) was evaluated in 64 stage IE gastric MALT lymphoma patients. We detected CagA expression in 31 (48.4%) of 64 patients: 26 (68.4%) of the 38 HP-dependent cases and 5 (19.2%) of the 26 HP-independent cases (P<0.001). Patients with CagA expression responded to HPE quicker than those without (median time to complete remission, 3.0 vs 6.5 months, P=0.025). Our results indicated that CagA can be translocated into malignant B cells of MALT lymphoma, and the translocation is clinically and biologically significant.

Chemokine receptors in gastric MALT lymphoma: loss of CXCR4 and upregulation of CXCR7 is associated with progression to diffuse large B-cell lymphoma

Chemokine receptors have a crucial role in the development and progression of lymphoid neoplasms. To determine the chemokine receptor expression profile in gastric mucosa-associated lymphoid tissue (MALT) lymphoma, we performed an expression analysis of 19 chemokine receptors at mRNA levels by using real-time RT-PCR, as well as of five chemokine receptors—CCR8, CCR9, CXCR4, CXCR6 and CXCR7—by immunohistochemistry on human tissue samples of Helicobacter pylori-associated gastritis, gastric MALT lymphoma and gastric extranodal diffuse large B-cell lymphoma originating from MALT lymphoma (transformed MALT lymphoma). Following malignant transformation from H. pylori-associated gastritis to MALT lymphoma, an upregulation of CCR7, CXCR3 and CXCR7, and a loss of CXCR4 were detected. The transformation of gastric MALT lymphomas to gastric extranodal diffuse large B-cell lymphoma was accompanied by upregulation of CCR1, CCR5, CCR7, CCR8, CCR9, CXCR3, CXCR6, CXCR7 and XCR1. Remarkably, CXCR4 expression was exclusively found in nodal marginal B-cell lymphomas and nodal diffuse large B-cell lymphomas but not at extranodal manifestation sites, ie, in gastric MALT lymphomas or gastric extranodal diffuse large B-cell lymphomas. Furthermore, the incidence of bone marrow infiltration (16/51 with bone marrow involvement vs 35/51 with bone marrow involvement; Spearman ρ=0467 P<0.001) positively correlated with CXCR4 expression. CXCL12, the ligand of CXCR4 and CXCR7, was expressed by epithelial, endothelial and inflammatory cells, MALT lymphoma cells and was most strongly expressed by extranodal diffuse large B-cell lymphoma cells, suggesting at least in part an autocrine signaling pathway. Our data indicate that CXCR4 expression is associated with nodal manifestation and a more advanced stage of lymphomas and hence, might serve as useful clinical prognostic marker.

1075P - Detection of Caga Expression in Gastric Mucosa-Associated Lymphoid Tissue Lymphoma—Biologic Significance and Clinical Implication

ABSTRACT Background We recently reported that a direct contact of Helicobacter pylori (HP) with B cells resulted in CagA translocation into the cells (Cancer Res 2010;70:5740-8). The translocated CagA further activates extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), and up-regulates the expressions of Bcl-2 and Bcl-xL. In this study, we sought to verify if CagA exists in the malignant B cells of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods Expression of CagA protein, phospho-SHP-2, phospho-ERK, phospho-p38MAPK, Bcl-2 and Bcl-xL in a series of 26 gastric MALT lymphoma was determined by immunohistochemistry. Western blot analysis was done to confirm immunohistochemical detection of CagA and biopsies from non-gastric MALT lymphoma served as negative controls. The association of CagA expression and the tumor response to HP-eradication (HPE) therapy was evaluated in 77 stage IE/IIE1 low-grade gastric MALT lymphoma patients. Results The expression of CagA was detected in 35 (45.5%) of 77 patients. CagA expression was closely associated with the expression phospho-SHP-2 (P = .016), phospho-ERK (P Conclusion CagA protein can be translocated into malignant B cells of MALT lymphoma. The expression of CagA in lymphoma cells appears to be biologically and clinically significant. Disclosure All authors have declared no conflicts of interest.

Apoptotic-related gene expression in oxaliplatin-treated CCM-1 colorectal adenocarcinoma and MALT-nt-1 mucosa-associated lymphoid tissue lymphoma cell lines

The purpose of this study was to assess the apoptotic -related gene expression of single-agent oxaliplatin in vitro. Growth inhibition studies were performed using the human cerebral cavernous malformation-1 colorectal adenocarcinoma cell line and mucosa-associated lymphoid tissue-nt-1 lymphoma cell line. At 50% inhibitory concentrations, oxaliplatin displayed suppressive effects toward Bcl-2 and the surviving expression in human cancer cell lines, whereas the expression of Fas/FasL was completely abolished in peripheral blood cells. Our data showed that oxaliplatin exerts potent antiapoptotic effects in human normal peripheral blood mononuclear cells at the suprapharmacologic concentration, warranting further investigations in the role of autoimmune adverse events while being used in numerous cycles for the treatment of malignancies.

Two Cases of Gastric MALT Lymphoma Diagnosed at Long Last after Successful Eradication ofHelicobacter pylori

The gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a rare disease. Helicobacter pylori infection is known as an important etiologic factor of the pathogenesis of MALT lymphoma. H. pylori colonization at the epithelium of gastric mucosa induces T cell and B cell recruitment. T cell induced B cell proliferation develops the MALT in the gastric mucosa. Monoclonal proliferation of B cell in the MALT transform into MALT lymphoma. The eradication of H. pylori is known to induce remission of the disease in more than 80% of patients. But there is no report on progression and development of MALT lymphoma after H. pylori eradication. We experienced two cases of gastric B cell MALT lymphoma diagnosed at long last, after the successful eradication of H. pylori. (Korean J Helicobacter Up Gastrointest Res 2012;12:265-270)

Immunohistochemical comparison of CD5, lambda, and kappa expression in primary and recurrent buccal Mucosa-associated lymphoid tissue (MALT) lymphomas

Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal marginal zone B-cell lymphoma and is a distinct subtype of non-Hodgkin's lymphoma.Primary MALT lymphomas can also occur in the oral cavity, although their appearance in this location is rare. The neoplastic cells of which MALT lymphomas are composed express B-cell antigens and show monotypic immunoglobulin expression with light-chain restriction.Although neoplastic MALT lymphoma cells do not express CD5, previous studies have shown that CD5 positive MALT lymphomas are more prone to dissemination than those that do not express CD5. Moreover, there are some reports that describe kappa- and lambda- dual light chain expression in B cell malignant neoplasms.A 66-year-old Japanese woman with swelling of the right buccal mucosa was referred to our hospital. The lesion was excised and was pathologically diagnosed as a MALT lymphoma tumor with a t(11;18)(q21;q21) chromosome translocation.Swelling of the right buccal mucosa recurred 2 years later. The recurrent tumor was then excised and pathologically diagnosed as MALT lymphoma.Immunohistochemical examination of CD5, lambda, and kappa expressions revealed that the primary tumor was positive for CD5, kappa, and lambda, but the recurrent tumor was weakly positive for CD5 and kappa.With respect to lambda positivity, the recurrent tumor showed negativity.Our study suggests that immunohistochemical expression of CD5, kappa, and lambda in oral MALT lymphoma have the risk of recurrence.We first described the recurrence of CD5 positive MALT lymphoma in the oral cavity and compared the immunohistochemical expressions of CD5, lambda, and kappa between the primary and recurrent tumors.

Establishment of a novel MALT lymphoma cell line, ma‐1, from a patient with t(14;18)(q32;q21)‐positive Helicobacter Pylori‐Independent Gastric MALT Lymphoma

Although t(11;18)(q21;q21), t(1;14)(p22;q32), and a few other genetic mutations are specific markers for the Helicobacter pylori (HP)-independent status of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the molecular mechanisms responsible for HP-independence of gastric MALT lymphoma without such translocations and mutations remain uncharacterized. In the present study, we describe the establishment and characterization of a novel MALT lymphoma cell line, MA-1, which was derived from a gastric MALT lymphoma which was negative for both t(11;18)(q21;q21) and t(1;14)(p22;q32); the patient had failed HP eradication therapy and chemotherapy. The cell morphology and the immunophenotype of this cell line were similar to that of the original gastric MALT lymphoma. Comparative genomic hybridization analysis showed no significant gene copy number changes. Spectral karyotyping displayed a near-diploid chromosome content (48 < 2n>XY), with at least 13 chromosome structural abnormalities. Furthermore, fluorescence in situ hybridization analyses disclosed the existence of three sub-clones, characterized by t(14;18)(q32;q21)/IGH-BCL2, t(14;18)(q32;q21)/IGH-MALT1, and the presence of both chromosomal translocations in the same cell, respectively; whereas amplification of the genes CRAD9, TRAF2, and BCL10 were not found. In conclusion, we have established the first human gastric MALT lymphoma cell line, which is characterized by unusual and complex chromosome translocations and will be useful to explore further the molecular mechanisms of HP-independence in gastric MALT lymphoma.

Ileal Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma with a Large-Cell Component That Regressed Spontaneously

Reported herein is a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the terminal ileum with a large-cell component, which regressed spontaneously. To the best of our knowledge, only five cases of spontaneously regressing MALT lymphoma have been reported in the English-language literature, and all of these cases were low-grade lymphomas. Spontaneous regression of a MALT lymphoma with a high-grade component is very rare. The present case suggests that MALT lymphoma cells have a reversible nature, even in the presence of a high-grade component.

Expression of thyroglobulin on follicular dendritic cells of thyroid mucosa-associated lymphoid tissue (MALT) lymphoma.

Reportedly, thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Hashimoto's thyroiditis. However, it remains unknown which antigen is closely associated with thyroid MALT lymphoma. We examined whether B cell response to thyroglobulin (Tg), which is a common thyroid-specific autoantigen, is related etiologically to the pathogenesis of thyroid MALT lymphoma. Expression of human Tg antigens and Cluster of differentiation (CD) 35 was examined immunohistochemically in 15 cases of thyroid MALT lymphoma using paraffin-embedded, formalin-fixed tissue specimens. In all cases of thyroid MALT lymphoma, human Tg was detected immunohistochemically in the follicular epithelial cells and follicular dendritic cells (FDCs). These FDCs were positive by double immunostaining for anti-human Tg rabbit polyclonal antibody (Ab) and for CD35. Results showed that the Tg, a thyroid autoantigen, had immunostained the germinal center of the thyroid MALT lymphoma. The Tg was present in the FDCs, as revealed by the staining pattern of the germinal center;this fact was confirmed by double immunostaining of anti-human Tg mouse monoclonal Ab and anti-CD35 mouse monoclonal Ab. The results of our study suggest that Tg is an autoantigen that is recognized by thyroid MALT lymphoma cells.

Significance of CXCR3 expression in gastric low‐grade B‐cell lymphoma of mucosa‐associated lymphoid tissue type for predicting responsiveness to Helicobacter pylori eradication

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct low-grade lymphoma that often regresses upon Helicobacter pylori eradication. It was reported that the chemokine receptor CXCR3 is expressed not only on activated T cells, but also on MALT lymphoma cells, and that CXCR3-positive B lymphocytes migrate or home to the MALT of MALT lymphoma. In the present study, we aimed to elucidate the correlation between CXCR3 expression and the clinicopathological features of gastric MALT lymphoma, and to determine whether CXCR3 expression was predictive of responsiveness to H. pylori eradication. Sixty-seven patients with gastric MALT lymphoma in a single-center study were treated with H. pylori eradication therapy. We evaluated the correlation of CXCR3 expression with response to H. pylori eradication therapy by logistic regression stratified according to potential confounders. Immunohistochemical analysis revealed that 28 of 67 cases (42%) were positive for CXCR3 expression. CXCR3 expression was significantly more prevalent in those without H. pylori infection, advanced-stage disease, and in those with API2-MALT1 fusion. In overall analysis, those with CXCR3 expression showed a significantly increased risk of non-responsiveness to H. pylori eradication therapy (odds ratio = 28.6; 95% confidence interval 5.70-143.4) compared to those without CXCR3 expression. This higher risk was observed consistently regardless of sex, API2-MALT1 fusion, H. pylori infection, or clinical stage. We showed that CXCR3 expression was an independent predictive factor for non-responsiveness to H. pylori eradication therapy in patients with gastric MALT lymphoma.