Low-grade Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

Long-term clinical outcomes of gastric mucosa-associated lymphoid tissue lymphoma in real-world experience

This long-term, retrospective, single-center study evaluated real-world clinical outcomes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma using different therapeutic modalities and analyzed factors affecting survival outcomes and long-term prognosis. We enrolled 203 patients with pathologically confirmed low-grade gastric MALT lymphoma and examined their treatment responses. Helicobacter pylori eradication was performed in all patients with H. pylori infection (HPI) and localized stage gastric MALT lymphoma. All patients underwent pre-treatment and physical evaluations, with complete blood count, biochemistry panel, and staging workup. Among 144 HPI-positive patients with stage I or II1–2 disease who underwent H. pylori eradication, 112 (77.8%) achieved complete remission (CR). All HPI-negative patients who received first-line radiotherapy achieved CR (100%), but only 22 of 27 first-line chemotherapy-treated patients achieved CR (81.5%). Lesions in the proximal upper-third or in multiple locations and an invasion depth to the submucosa or deeper were associated with poor response to eradication, and HPI negativity was significantly correlated with poor progression-free survival. HPI eradication treatment should be the first-line treatment for patients with localized stage HPI-positive gastric MALT lymphoma. The “watch-and-wait” strategy should be adopted for delayed responders. We suggest radiotherapy for patients with a localized HPI-negative status or when eradication has failed.

Primary Esophageal Lymphoma: A Histopathological Experience from Two Tertiary Hospitals, Western Saudi Arabia.

Primary esophageal lymphoma (PEL) is a rare disorder. The objective of this study was to document the clinicopathological features of PEL at two tertiary hospitals in the western region of the Kingdom of Saudi Arabia. All PELs diagnosed between May 2002 and June 2022 were retrieved. Histopathological and immunohistochemical slides were reviewed. Additional immunohistochemistry stains were performed in selected cases. Follow-up data were collected. There were only eight cases of PEL in the records of the two hospitals. The age of the patients ranged between 50 and 74 years (median 62 years and mean 62.5 years). There were six males (80%) and two females (20%). None of the patients were immunocompromised or had human immunodeficiency virus (HIV) infection. The clinical manifestation included dysphagia and loss of weight. Six cases were diffuse large B-cell lymphoma (DLBCL), and two were low-grade mucosa-associated lymphoid tissue lymphoma. PEL is an extremely rare disease with male predominance. DLBCL is the most common pathological type in our community. There was no relation to immune status or HIV infection in this series. Clinical presentations were typically dysphagia with weight loss. Further reporting of PEL cases might help explain this disease and improve its diagnosis and management.

The outcome of radiation therapy as a primary treatment in orbital lymphoma: a systematic review.

BackgroundThe extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) is the most common orbital and adnexal lymphomas. Radiotherapy is one of the most preferred treatment options for orbital lymphomas since they are localized and radiation sensitive. The objective of this study is to evaluate how radiation therapy affected the outcome of orbital MALT lymphoma.Materials and methodsPRISMA guideline was used to conduct this systematic review of electronic databases (PubMed, EMBASE and Cochrane Library), then we assessed the quality of evidence of each paper.ResultsTwenty-five studies were finally included. 94% studies were intended for definitive therapy and almost all of the studies used external radiation sources. The total doses given to the tumor bed ranged from 4 Gy to 55 Gy and were divided into three groups: ultra-low dose (4–6 Gy), standard-dose (24–30.6 Gy), and high-dose (> 30.6 Gy). 75–90% patients showed CR and local relapse was only reported at 3.5–5%. Higher 5-year PFS was reported in the patients group with lens shielding (90.1% vs. 82.1%) and an increase in Meiboscore after RT courses. Toxicities, including dry eye and cataract, were reported in several patients. Acute toxicities subsided gradually over a few months with artificial tears. The risk of early cataract formation increases in patients who received > 30 Gy and lower in the IMRT group.ConclusionRT is a successful primary definitive therapy for low-grade orbital MALT lymphoma, with a high survival rate, low recurrence rate, and typically acceptable toxicity.

Helicobacter pylori Eradication and Gastric Cancer Prevention

Since Warren and Marshall demonstrated Helicobacter pylori (H. pylori) as a cause of gastritis in the early 1980s, H. pylori has been associated with various gastric diseases, including gastric ulcer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, gastric adenoma, gastric adenocarcinoma, and hyperplastic gastric polyps. H. pylori eradication therapy can treat some associated diseases, including low-grade gastric MALT lymphoma, and significantly reduce the risk of peptic ulcer recurrence or progression of atrophic gastritis and intestinal metaplasia. In East Asia, where H. pylori and gastric cancer are prevalent, several studies have been conducted to prove whether the risk of gastric cancer development is reduced through H. pylori eradication therapy. Early studies failed to show the benefits of H. pylori eradication therapy in gastric cancer prevention. However, recent studies with extended follow-up periods have reported reduced risks of gastric cancer after treatment of H. pylori infection. H. pylori eradication therapy effectively prevents gastric cancer even in patients who were treated for early gastric cancer, and can be used in treating hyperplastic gastric polyps. Herein, we reviewed current evidence supporting the benefits of H. pylori eradication therapy to help clinicians understand its impact on gastric cancer prevention and hyperplastic polyp treatment.

The Helicobacter pylori CagY Protein Drives Gastric Th1 and Th17 Inflammation and B Cell Proliferation in Gastric MALT Lymphoma.

Background: the neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to H. pylori, however, the nature of the H. pylori antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the H. pylori antigen able to drive B cell proliferation. Methods: the B cells and the clonal progeny of T cells from the gastric mucosa of five patients with MALT lymphoma were compared with those of T cell clones obtained from five H. pylori–infected patients with chronic gastritis. The T cell clones were assessed for their specificity to H. pylori CagY, cytokine profile and helper function for B cell proliferation. Results: 22 of 158 CD4+ (13.9%) gastric clones from MALT lymphoma and three of 179 CD4+ (1.7%) clones from chronic gastritis recognized CagY. CagY predominantly drives Interferon-gamma (IFN-γ) and Interleukin-17 (IL-17) secretion by gastric CD4+ T cells from H. pylori-infected patients with low-grade gastric MALT lymphoma. All MALT lymphoma-derived clones dose dependently increased their B cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1. Conclusion: the results obtained indicate that CagY drives both B cell proliferation and T cell activation in gastric MALT lymphomas.

Nuclear expression of BCL10 or nuclear factor kappa B helps predict Helicobacter pylori–independent status of low-grade gastric mucosa–associated lymphoid tissue lymphomas with or without t(11;18)(q21;q21)

AbstractThe t(11;11212121212127)(q21;q21) translocation is a specific marker for Helicobacter pylori–independent status of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there are no reliable markers to predict tumor response to H pylori eradication in patients without t(11;18)(q21;q21). Nuclear expression of BCL10 and nuclear factor kappa B (NF-κB) was recently found to be closely associated with H pylori–independent status of the high-grade counterpart of gastric MALT lymphoma, which usually lacks t(11;18)(q21;q21). This study examined whether these 2 markers can also predict H pylori–independent status of low-grade gastric MALT lymphomas without t(11; 18)(q21;q21). Sixty patients who underwent successful H pylori eradication for low-grade gastric MALT lymphomas were included. Forty-seven (78.3%) patients were negative for t(11;18)(q21;q21); among them, 36 (76.6%) were H pylori dependent and 11 (23.4%) were H pylori independent. Nuclear expression of BCL10 was significantly higher in H pylori–independent than in H pylori–dependent tumors (8 of 11 [72.7%] vs 3 of 36 [8.3%]; P < .001). Nuclear expression of NF-κB was also significantly higher in H pylori–independent than in H pylori–dependent tumors (7 of 11 [63.6%] vs 3 of 36 [8.3%]; P < .001). Further, nuclear translocation of BCL10 and NF-κB was observed in 12 of the 13 patients with t(11;18)(q21;q21), and all these 12 patients were H pylori independent. In summary, nuclear expression of BCL10 or NF-κB is predictive of H pylori–independent status of low-grade gastric MALT lymphoma with or without t(11;18)(q21; q21).

Association of Pulmonary MALT Lymphoma and Sarcoidosis

Introduction Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by the chronic inflammation. Mucosa associated lymphoid tissue (MALT) lymphoma is a low-grade marginal zone B-cell lymphoma of MALT often etiologically associated with chronic inflammation in the underlying organ. A rare association between sarcoidosis and MALT lymphoma has been reported. Case Description We present the case of a 75-year-old woman who presented with chronic cough and dyspnea of several years' duration. She was found to have fluctuating lung infiltrates on serial imaging studies. A bronchial biopsy revealed chronic inflammation, and no evidence of infection. She was then treated with oral steroids with a transient benefit. However, the infiltrate and symptoms recurred, therefore 8 months later, she underwent repeat imaging. This showed a relapse of the infiltrate and enlarged mediastinal lymphadenopathy. The lung infiltrate was biopsied (percutaneously). This demonstrated a MALT lymphoma. Imaging studies done for staging showed a large retroperitoneal lymph node. A biopsy of this node revealed non-caseating granulomas, consistent with sarcoidosis. Chemotherapy with bendamustine and rituximab was initiated for therapy of the MALT lymphoma. Discussion A rare association between pulmonary MALT lymphoma and underlying inflammation caused by sarcoidosis has been previously described. In our patient, sarcoidosis was diagnosed in a biopsy of a retroperitoneal lymph node, but we suspect that there is likely involvement of the mediastinal nodes. Disclosures Rao: Bayer &amp; Daiichi Sankyo:Consultancy.Daniel:GSK:Other: Paid speaker for COPD medications.

PRIMARY SJOGREN SYNDROME CAUSING PULMONARY EXTRANODAL MARGINAL CELL LYMPHOMA

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Extranodal marginal zone lymphoma (MZL) of the lung is a rare pulmonary lymphoid malignancy and World Health Organization (WHO) classifies Mucosa associated lymphoid tissue (MALT) lymphoma as a subtype of B-cell MZL. CASE PRESENTATION: 80 year old Caucasian male with past medical history of obstructive sleep apnea, chronic kidney disease stage III, type II diabetes mellitus, hypertension and tobacco abuse, was first seen in pulmonary clinic for asymptomatic innumerate bilateral pulmonary nodules noted on Computed Tomography (CT) scan of the chest. He complained of occasional chronic dry mouth on further questioning. Antibody testing was positive for Antinuclear antibodies (245 AU/ml) and SS Ro antibody (188 AU/ml). His dry mouth and lower lobe predominant cystic and nodular changes were concerning for lymphoid interstitial pneumonia associated with Sjogren's syndrome. He was referred to rheumatology then subsequently lost to follow up. He presented two years later with increased shortness of breath and progressive weight loss. Pulmonary function tests (PFTs) showed an isolated low diffusing capacity for carbon monoxide at 33% predicted (down from 75% prior). CT scan revealed progression of his bilateral lung nodules and cystic changes in the lower lungs bilaterally. He then underwent bronchoscopy and surgical lung biopsy. This showed a low-grade B- cell lymphoma with plasmacytic differentiation, most consistent with MALT stage 1E Extranodal marginal zone lymphoma. Patient was started on rituximab weekly for 4 weeks and reported some improvement in his sicca symptoms. DISCUSSION: Roughly 10 to 20 percent of SS patients have clinically significant lung disease defined by symptoms most commonly cough and dyspnea. Abnormal imaging and PFTs are common. Thin-walled lung cysts are detected with CT imaging in 12 to 46 percent of SS patients. Interstitial lung disease can occur in SS in several forms (1). In a series of thirteen patients with pulmonary MALT lymphoma performed by Yachoui et. al, 54% were positive for primary sjogren syndrome (PSS) (2). No difference in outcomes was noted on two large retrospectives studies involving different treatment modalities including surgery, chemotherapy or combined therapy. Asymptomatic patients should be observed with no treatment indicated initially. It is indicated for patients with a high burden of lymphadenopathy with splenomegaly, organ dysfunction, bone marrow suppression, and/or rapid disease progression (3). Series performed by Yachoui et. al demonstrated a favorable prognosis in all cases of pulmonary MALT lymphoma with all treatment modalities resulting in complete and sustained response (2). CONCLUSIONS: SS can have wide ranging organ involvement. Prompt referral to rheumatology and active monitoring is paramount. Further investigation is warranted to better understand pulmonary MALT pathogenesis, treatment, and outcomes in PSS. Reference #1: Stojan, G., et al. (2013). “Pulmonary manifestations of Sjögren's syndrome.” Current allergy and asthma reports 13(4): 354-360. Reference #2: Yachoui R, Leon C, Sitwala K, Kreidy M. Pulmonary MALT lymphoma in patients with Sjögren's syndrome. Clinical medicine & research. 2017;15(1-2):6-12. Reference #3: Pinotti G, Zucca E, Roggero E, Pascarella A, Bertoni F, Savio A, et al. Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma. Leukemia & lymphoma. 1997;26(5-6):527-37

A case of Barrett\u2019s esophageal cancer with gastric mucosa-associated lymphoma

BackgroundAlthough the first-line therapy for early-stage gastric mucosa-associated lymphoid tissue lymphoma is the eradication of Helicobacter pylori, the effect of eradication in Helicobacter pylori-negative cases is unclear. In this case report, we describe a surgical option for a case of Barrett’s esophageal cancer with concurrent gastric mucosa-associated lymphoid tissue lymphoma.Case presentationA 79-year-old man was admitted to our hospital with Barrett’s esophageal cancer and gastric mucosa-associated lymphoid tissue lymphoma. Initially, we performed endoscopic submucosal dissection for Barrett’s esophageal cancer. Since residual tumor was observed after the endoscopic submucosal dissection, we performed an esophagectomy with two-field lymph node dissection, which was followed by placement of a gastric conduit via the posterior mediastinal route. He was discharged 14 days after surgery. Although no additional treatment exists for mucosa-associated lymphoid tissue lymphoma, no recurrent disease has been detected to date.ConclusionAn option to use a portion of the stomach with low-grade malignant mucosa-associated lymphoid tissue lymphoma as a conduit after esophagectomy was suggested.

Clinical efficacy of the modified Helicobacter pylori eradication therapy for Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: a meta analysis.

BackgroundHelicobacter pylori (HP) has been considered to be one of the primary causes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma since 1993. Low-grade gastric MALT lymphoma with HP is widely treated with HP eradication therapy, according to each specific clinical situation. However, several studies and guidelines indicate that the modified HP eradication therapy is also valid for HP-negative gastric MALT lymphoma. The aim of this study was to perform a meta-analysis of the clinical efficacy of the modified HP eradication therapy for gastric MALT lymphoma without HP.MethodsWe searched studies that reported the response rate of the modified HP eradication therapy regimen for gastric MALT lymphoma without HP by using PubMed, Medline, and Ebsco from January 1971 until February 2019. All statistical analyses were carried out using R 3.5.3 (Mathsoft Company, Cambridge, MA, USA). The pooled response rate was expressed as a decimal. The heterogeneity test was performed using the I-squared (I2) statistic.ResultsA total of 14 studies were selected with a total of 148 patients with HP-negative gastric MALT lymphoma. The overall pooled response rate was 0.38 (95% confidence interval [CI]: 0.29–0.47). The combined estimate is I2 = 57% (P < 0.01). The study subjects were categorized by factors (area of patients). The pooled response rate of the sub-groups (Korea, Japan, China, and Western countries) was 0.63 (95% CI: 0.50–0.76), 0.16 (95% CI: 0.05–0.30), 0.38 (95% CI: 0.20–0.55), and 0.57 (95% CI: 0.08–1.00). The response rate showed that the modified HP eradication therapy was effective for patients with HP-negative gastric MALT lymphoma, especially in Korea and Western countries.ConclusionTherefore, the modified HP eradication therapy can be considered an optional therapy for patients with low-grade HP-negative gastric MALT lymphoma. However, several limitations were revealed in the meta-analysis. Further systematic reviews and research are required.

Low-grade gastric mucosa-associated lymphoid tissue lymphoma: Clinicopathological factors associated with Helicobacter pylori eradication and tumor regression.

353 Background: Eradication of Helicobacter pylori is widely accepted as the initial therapy for low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The aim of this study was to assess the remission and relapse rates of low-grade gastric MALT lymphoma after H. pylori eradication and to identify the clinical factors affecting remission. Methods: We retrospectively analyzed 151 patients diagnosed with gastric MALT lymphoma from May 2003 to December 2018. Results: Of the 151 patients, 112 (74.2%) had an H. pylori infection. Total regression rates with eradication was 90.2% (101/112) in H. pylori-positive patients and 55% (11/20) in H. pylori-negative patients. Age, sex, tumor location, endoscopic findings, and the severity of mononuclear lymphocytes were not related to achieving successful initial H. pylori eradication and remission. However, patients with a smaller H. pylori burden ( p=0.030) and less neutrophil infiltration ( p=0.003) were more likely to achieve a successful initial H. pylori eradication. H. pylori ( p&lt;0.001) and the burden ( p=0.020) were significantly related to remission of MALT lymphoma. Conclusions: The results show that H. pylori burden and neutrophil infiltration were inversely related to the success of the initial H. pylori eradication procedure and that the H. pylori burden was inversely related to the remission of MALT lymphoma.

Heterogeneity of clinical management of low-grade gastric lymphoma of mucosa-associated lymphoid tissue. An audit of 198 patients in Spain

IntroductionCure of Helicobacter pylori infection in patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT) leads to long-term clinical remission in the initial stages. As it is a rare disease, its management in clinical practice remains largely unknown and heterogeneity of care remains a concern.The aim was to audit the management and evolution of a large series of low-grade gastric MALT lymphomas from thirteen Spanish hospitals. Materials and methodsMulticentre retrospective study including data on the diagnosis and follow-up of patients with gastric low-grade MALT lymphoma from January 1998 to December 2013. Clinical, biological and pathological data were analyzed and survival curves were drawn. ResultsOne-hundred and ninety-eight patients were included. Helicobacter pylori was present in 132 (69%) patients and 103 (82%) in tumors confined to the stomach (stage EI) and was eradicated in 92% of patients. Chemotherapy was given in 90 (45%) patients and 43 (33%) with stage EI. Marked heterogeneity in the use of diagnostic methods and chemotherapy was observed. Five-year overall survival was 86% (89% in EI). Survival was similar in EI patients receiving aggressive treatment and in those receiving only antibiotics (p=0.577). DiscussionGastric MALT lymphoma has an excellent prognosis. We observed, however, a marked heterogeneity in the use of diagnostic methods or chemotherapy in early-stage patients.

1081P - Efficacy of salvage therapy in the treatment of Helicobacter pylori-positive gastric low-grade mucosa-associated lymphoid tissue lymphoma

BackgroundHelicobacter pylori (H.pylori) infection has a critical role in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and its eradication can lead to tumor regression. However, in patients who do not achieve a lymphoma regression or relapse following antibiotic therapy, outcome of the patients are scarce. We evaluated the long-term outcome of the patients who received salvage therapy with relapsed or refractory gastric MALT lymphoma. MethodsBetween June 2000 and June 2017, a total of 29H.pylori-positive gastric MALT lymphoma patients who received frontline H.pylori eradication were included in this study. H.pylori-positive status was defined by positive results for the biopsy urease test and histology. They had all been diagnosed by endoscopy and had a complete staging including CT-scan. Patients received standard triple therapy for eradication of H.pylori and after treatment were sequentially followed-up with endoscopies performed to evaluate the response. Tumors that had resolved to complete remission (CR) score of GELA histologic grading system were considered treatment-responsive. ResultsDuring the follow-up periods 16 patients were refractory, nine had probable minimal residual disease and four relapsed after the first-line antibiotics. Of these 29 patients, transformation into high-grade B-cell lymphoma did not occur. Among the non-responder and relapsed patients, three patients were subjected to a watch and wait, while 26 patients underwent second-line treatment including radiotherapy (n=20), chemotherapy (n=5), chemotherapy plus sequential radiotherapy (n=1). Of the 20 patients treated with radiotherapy, the median dose to stomach was 3060 cGy (range, 1620-5000 cGy). After radiotherapy a CR was achieved in 20 patients (100%). Among six patients who received chemotherapy, a CR was achieved in five patients and no change was in one. That patient was achieved CR after radiotherapy. Probabilities of freedom from treatment failure and overall survival after 10 years were 100% and 83%. ConclusionsOutcome of patients with first-line H.pylori eradication failure followed by delayed chemotherapy and/or radiotherapy on indication was excellent. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

3229 Helicobacter pylori-Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphomas: A Challenge in Treatment Options

INTRODUCTION: Primary gastric lymphoma is a rare entity of which the specific variant, mucosa-associated lymphoid tissue (MALT) lymphomas may be the best recognized given its association with Helicobacter pylori (H. pylori) infection. It has been thought that repetitive immune stimulation from underlying infection is influential in the pathogenesis of this tumor. However up to 10% of gastric MALT lymphomas are diagnosed without a concomitant H. pylori infection. The pathogenesis and management of H. pylori-negative gastric MALT lymphomas remains uncertain. CASE DESCRIPTION/METHODS: 65 year old woman with Celiac disease and GERD presented with worsening severe reflux and epigastric pain. She underwent EGD which revealed multiple superficial ulcers in the cardia with notable nodularity, ulceration, and friability. Cold forceps biopsies of the abnormal mucosa demonstrated diffuse atypical small B-Cell lymphoid infiltrate with features compatible with low grade MALT lymphoma. Of note, immunostain for H. Pylori was negative. Subsequent H. pylori stool antigen assay as well H. pylori IgG, IgM, and IgA were all negative. Given her negative antibodies indicating she truly had no exposure to H. Pylori, the patient has been referred to oncology for multidisciplinary management. DISCUSSION: This case of early stage gastric MALT lymphoma without evidence of active H. pylori infection elucidates that there is limited literature for the management for these patients. Studies have suggested that H. pylori eradication therapy can be efficacious for a proportion of H. pylori-negative gastric MALT lymphomas, possibly due to a false negative detection by biopsy. Local radiation therapy with curative intent and single agent rituximab therapy rather than H. pylori eradication have also been explored as alternate options. The data stems from retrospective studies and single agent prospective trials. Thus, there may be a role for future research directly comparing treatment strategies for optimal management of this clinical entity.

2707 Gastric Mucosa-Associated Lymphoid Tissue Lymophoma Treated by Endoscopic Mucosal Resection

INTRODUCTION: Primary low-grade gastric Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinctive type of B-cell lymphoma. Endoscopic appearances of low-grade gastric MALT lymphoma are quite varied and polypoid or subepithelial type (exophytic) is rare. Here, we reported the case of H. pylori negative gastric MALToma presenting as an exophytic subepithelial tumor, diagnosing and treating by endoscopic mucosal resection (EMR). CASE DESCRIPTION/METHODS: A 53-year-old man was referred to our hospital because of a large subepithelial tumor of the stomach, which was incidentally found on an endoscopy for a routine checkup in outside hospital. Initial outside endoscopic biopsy was a simple chronic gastritis. Physical examination and laboratory results were unremarkable. On endoscopic examination, a 2.0 cm sized round and hard exophytic subepithelial tumor was seen on the great curvature side of high body of the stomach. The tumor showed a well-demarcated smooth border without any erosion and ulceration. An abdominal pelvic CT demonstrated an enhancing subepithelial tumor without regional lymphadenopathy, such as gastrointestinal stromal tumor. EUS showed a hypoechoic and heterogeneous mass in the 2nd and 3rd layer with ill-defined internal margin. EMR was done for both the definite diagnosis and the treatment without complications because the tumor had a semipedunculated morphology. Results of a histopathologic examination of the resected tumor showed diffuse lymphocytic proliferation in the submucosa mimicking a subepithelial tumor with lymphoepithelial lesions. Dense lymphocytic infiltration composed of mainly B cells forming vague follicular colonization. Immunohistochemical stain of cytokeratin also showed presence of lymphoepithelial lesions. The Ki-67 was positive in 7%. Histologically, no H. pylori was observed in the luminal side. Finally, the patient was diagnosed as a H. pylori–negative extranodal marginal zone B-cell lymphoma (MALToma) (stage EI1). No additional treatment such as chemotherapy or radiation was performed. The follow-up endoscopic examination showed no recurrence until 2 years after EMR. DISCUSSION: We suggest that EMR may be an alternative treatment modality in the diagnosis and the treatment of gastric MALT lymphoma in cases of submucosal or polypoid morphology type, especially when H. pylori is negative. Further study in terms of feasibility, efficacy, and long-term safety of EMR as a curative treatment would be warranted.

PB2021 GASTRIC MUCOSA‐ASSOCIATED LYMPHOID TISSUE LYMPHOMA: A MONOCENTRIC EXPERIENCE

Background:Mucosa‐associated lymphoid tissue (MALT) lymphoma accounts for 7‐8% of B‐cell lymphoma. Tumor proliferation consists of type B lymphomatous cells of low grade malignancy. They are considered indolent and are part of the marginal zone. They constitute the predominant histological type of non‐Hodgkin's malignant lymphoma of the stomach. Transformation into high‐grade lymphoma is rare.Aims:The aim of this study is to describe the clinical characteristics and the therapeutic results of MALT lymphoma.Methods:We reviewed retrospectively the records of 18 patients presenting with gastric MALT lymphoma treated between 1993 and 2018. Patients with low‐grade lymphoma in failure after helicobacter eradication had exclusive gastric external radiotherapy. Chemotherapy were indicated in case of high grade lymphoma transformation. Radiotherapy doses range between 30 and 40 Gy (2 Gy per fraction, five fractions per week).Results:Median age was 52 years old. All tumours were IE stage. Helicobacter pylori was positive in 15 cases. Three patients had other cancers (gastric adenocarcinoma, breast cancer, mantle lymphoma). All patients received antibiotic therapy (triple therapy in 12 cases and concomitant treatment in 7 cases) with responding residual disease in 6 cases and probable minimal residual disease in 9 cases. Second line antibiotherapy was pylera in 3 cases and levofloxacin with amoxicillin in 2 cases. Seven patients with low‐grade MALT lymphoma had radiotherapy. Four patients with high‐grade transformed lymphoma received chemotherapy. Seventeen patients are in complete remission after treatment achievement. Five and 10‐ year disease‐free survival are 100%.Summary/Conclusion:Eradication of Helicobacter pylori is the mainstay of treatment of gastric MALT lymphoma. The levocine‐amoxicillin combination with proton pump inhibitor seems to be effective as a second‐line treatment in case of non availability of the pylera. External irradiation is an effective and well‐tolerated treatment modality in case of resistance to helicobacter eradication. Immuno‐chemotherapy is indicated for diffuse lymphoma (stage III and IV) or in case of transformation into large cell lymphoma.

HRCT in primary pulmonary lymphoma: can CT imaging phenotypes differentiate histological subtypes between mucosa-associated lymphoid tissue (MALT) lymphoma and non-MALT lymphoma?

Primary pulmonary lymphoma (PPL) mainly comprises mucosa-associated lymphoid tissue (MALT) lymphoma as well as other subtypes of lymphoma. Different phenotypes of PPL demonstrate various high-resolution computed tomography (HRCT) features. We aimed to evaluate the value of HRCT in the diagnosis and differential diagnosis of PPL, especially between MALT lymphoma and non-MALT lymphoma and the correlation between CT and pathological features. We performed a retrospective analysis on 72 patients with PPL confirmed by pathology between 2007 and 2016. We compared the CT characteristics and correlation with pathological findings between MALT lymphoma and non-MALT lymphoma groups. All 72 patients with PPL were classified into two groups: low-grade MALT lymphoma (MALToma) (56/72) and high-grade non-MALT lymphoma (non-MALToma) (16/72). The latter group consisted of diffuse large B cell lymphoma (8/72), Hodgkin's lymphoma (3/72), T-cell lymphoma (4/72), and intravascular large B-cell lymphoma (1/72). A total of 168 lesions were analyzed, including 57 cases with multiple lesions and 15 cases with single lesion. The manifestation of four distribution patterns: nodular or mass-like involvement pattern, diffuse interstitial lung disease (DILD) pattern, pneumonia-like consolidative pattern and mixed pattern was not significantly different between MALToma and non-MALToma (all P>0.05). Signs of air bronchogram and CT angiogram occurred significantly more often in individuals with MALToma group than those with non-MALToma (75% vs. 25%, P=0.001; 64.3% vs. 12.5%, P<0.001; respectively). Conversely, the halo sign presented more often in non-MALToma than in MALToma patients (19% vs. 63.6%, P=0.02). In addition, the butterfly sign was only observed in four patients with MALToma. HRCT imaging phenotypes were beneficial in the diagnosis of PPL. Solitary or multifocal nodules/masses and consolidation were the most common imaging patterns. The air bronchogram sign, CT angiogram sign, halo sign, and butterfly sign could be potential to help to differentiate MALToma from non-MALToma.

Characterization and outcomes of local treatment for primary bladder lymphoma: A population-based cohort analysis.

Introduction:Primary bladder lymphoma (PBL) is rare, representing 0.2% of extranodal lymphoma and less than 1% of all tumors originating in the bladder. Since the initial description of the disease, low-grade mucosa-associated lymphoid tissue (MALT) lymphoma has been reported as the most common subtype while high-grade disease was thought to represent only 20% of the reported cases.Materials and Methods:One hundred and ninety five patients with PBL from the Surveillance, Epidemiology, and End Results (SEER) registry from 1998-2010 were reviewed. Tumors were classified as high or low grade based on histologic subtype of lymphoma based on revised European-American Lymphoma classification system. Socio-demographic and clinical variables were reported, as well as survival outcome analyses using the Kaplan-Meier method and log-rank test. Cox proportional hazard analysis was used to generate hazard ratios for risk factors associated with mortality.Results:Eighty-three patients (42.6%) with low-grade and 112 patients (57.4%) with high-grade bladder lymphoma were studied. There were no differences between the low and high-grade groups for socio-demographic or clinical variables. Median overall survival or patients with low-grade disease was 38 months versus 15 months for patients with high-grade disease (p< 0.001). Analysis demonstrated worse survival outcomes for patients with high-grade disease compared to low-grade disease (p< 0.001). On multivariable analysis, increasing age and high-grade disease were associated with worse disease specific mortality (p< 0.001).Conclusion:Patient with high-grade primary bladder lymphoma had worse survival outcomes compared to those with low-grade disease. While transurethral resection provides tissue for diagnosis, immunotherapy/chemotherapy remains the mainstay of treatment for bladder lymphoma. Consolidation chemotherapy has been recommended in young patients not achieving complete remission with immunotherapy/chemotherapy.

The B-cell-activating factor signalling pathway is associated with Helicobacter pylori independence in gastric mucosa-associated lymphoid tissue lymphoma without t(11;18)(q21;q21).

We previously reported that activation of the B-cell-activating factor (BAFF) pathway upregulates nuclear factor-κB (NF-κB) and induces BCL3 and BCL10 nuclear translocation in Helicobacter pylori (HP)-independent gastric diffuse large B-cell lymphoma (DLBCL) tumours with evidence of mucosa-associated lymphoid tissue (MALT). However, the significance of BAFF expression in HP independence of gastric low-grade MALT lymphomas without t(11;18)(q21;q21) remains unexplored. Sixty-four patients who underwent successful HP eradication for localized HP-positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied. BAFF expression was significantly higher in the HP-independent group than in the HP-dependent group [22/26 (84.6%) versus 8/38 (21.1%); p < 0.001]. Similarly, BAFF receptor (BAFF-R) expression (p = 0.004) and nuclear BCL3 (p = 0.004), BCL10 (p < 0.001), NF-κB (p65) (p = 0.001) and NF-κB (p52) (p = 0.005) expression were closely correlated with the HP independence of these tumours. Moreover, BAFF overexpression was significantly associated with BAFF-R expression and nuclear BCL3, BCL10, NF-κB (p65) and NF-κB (p52) expression. These findings were further validated in an independent cohort, including 40 HP-dependent cases and 18 HP-independent cases of gastric MALT lymphoma without t(11;18)(q21;q21). The biological significance of BAFF signalling in t(11;18)(q21;q21)-negative lymphoma cells was further studied in two types of lymphoma B cell: OCI-Ly3 [non-germinal centre B-cell origin DLBCL without t(11;18)(q21;q21) cell line] and MA-1 [t(14;18)(q32;q21)/IGH-MALT1-positive DLBCL cell line]. In both cell lines, we found that BAFF activated the canonical NF-κB and AKT pathways, and induced the formation of BCL10-BCL3 complexes, which translocated to the nucleus. BCL10 and BCL3 nuclear translocation and NF-κB (p65) transactivation were inhibited by either LY294002 or by silencing BCL3 or BCL10 with small interfering RNA. BAFF also activated non-canonical NF-κB pathways (p52) through tumour necrosis factor receptor-associated factor 3 degradation, NF-κB-inducing kinase accumulation, inhibitor of κB kinase (IKK) α/β phosphorylation and NF-κB p100 processing in both cell lines. Our data indicate that the autocrine BAFF signal transduction pathway contributes to HP independence in gastric MALT lymphomas without the t(11;18)(q21;q21) translocation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Hepatic MALTOMA in a Case of Chronic Hepatitis C

Primary hepatic lymphoma (PHL) must be considered in any patient who presents with a liver mass or infiltration picture with cholestatic liver abnormality. The presence of constitutional symptoms and significant lymphadenopathy with Hepatitis C infection should invoke a search for PHL by liver biopsy (LB) as it is treatable. A 59-yr male presented with epigastric discomfort, fatigue, 30 lb. weight loss. Minimal alcohol use, 30-pack year smoking, no IVDU, blood transfusion but had a tattoo. He was afebrile, anicteric and had mild hepatomegaly with no lymphadenopathy. Laboratory work up showed elevated AST 112 U/L, ALT 333 U/L, with normal ALP 111 U/L, bilirubin 0.6 mg/dL, LDH 151 U/L, platelets 152,000/mm3, PT 11.1 sec, and INR 1.1. Iron studies, alpha 1 antitrypsin levels, ANA, AMA, and ASMA were normal. However, HCV was positive with HCV RNA of 2.3 million with genotype 2. Subsequent CT abdomen showed multiple enlarged lymph nodes within retroperitoneal and portacaval regions and a 1 cm hypo density in gall bladder (GB) wall. MRCP showed a contracted normal GB. LB confirmed mild chronic hepatitis, with lymphocytic portal inflammation with minimal fibrosis. EUS with biopsy confirmed benign intra-abdominal lymphadenopathy. Bone marrow biopsy showed no evidence of lymphoma. Immunohistochemistry on LB showed portal-based lymphocytic infiltrate with immunophenotype: CD20+ / BCL2+ / CD5- / CD10- / BCL6- / CD23- / cyclin D1-, with monoclonal pattern on immunoglobulin heavy chain gene rearrangement. A diagnosis of extra nodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) was made. We treated with sofosbuvir and ribavirin for 12 weeks and he achieved SVR 12. Repeat LB after 3 months after achieving SVR 12 confirmed reduced lymphocytic infiltration and our oncologist decided to observe him with no chemotherapy but his LFT's are normal and he was asymptomatic. PHL is a rare malignancy (0.016% of all non-Hodgkin lymphomas) and is often misdiagnosed. Among PHLs, low-grade marginal B-cell lymphoma (MZL) of MALT is extremely rare. Etiology of MZL is unclear HCV, HBV and EBV are implicated. Hepatic MZL affect middle-aged men and present with constitutional symptoms, hepatomegaly and cholestatic jaundice. LB compatible with lymphoma with no lymphoproliferative disease outside the liver is the presentation. Treating the primary infection and Chemotherapy with rituximab is standard.