Transformation of marginal zone lymphoma into high-grade B-cell lymphoma expressing terminal deoxynucleotidyl transferase:A case report

BACKGROUND High-grade B-cell lymphoma(HGBL)is an unusual malignancy that includes myelocytomatosis viral oncogene(MYC),B-cell lymphoma-2(BCL-2),and/or BCL-6 rearrangements,termed double-hit or triple-hit lymphomas,and HGBL-not otherwise specific(HGBL-NOS),which are morphologically characteristic of HGBL but lack MYC,BCL-2,or BCL-6 rearrangements.HGBL is partially transformed by follicular lymphoma and other indolent lymphoma,with few cases of marginal zone lymphoma(MZL)transformation.HGBL often has a poor prognosis and intensive therapy is currently mainly advocated,but there is no good treatment for these patients who cannot tolerate chemotherapy.CASE SUMMARY We reported a case of MZL transformed into HGBL-NOS with TP53 mutation and terminal deoxynucleotidyl transferase expression.Gene analysis revealed the gene expression profile was identical in the pre-and post-transformed tissues,suggesting that the two diseases are homologous,not secondary tumors.The chemotherapy was ineffective and the side effect was severe,so we tried combination therapy including venetoclax and obinutuzumab.The patient tolerated treatment well,and reached partial response.The patient had recurrence of hepatocellular carcinoma and died of multifunctional organ failure.He survived for 12 months after diagnosis.CONCLUSION Venetoclax combined with obinutuzumab might improve the survival in some HGBL patients,who are unsuitable for chemotherapy.

Marginal zone lymphoma with severe rashes: A case report

BACKGROUND Marginal zone lymphoma(MZL)is an indolent subtype of non-Hodgkin lymphoma(NHL),which is rare clinically with severe rashes as the initial symptom.CASE SUMMARY This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge.First-line treatment with rituximab combined with zanubrutinib had poor effects.However,after switching to obinutuzumab combined with zanubrutinib,the case was alleviated,and the rashes disappeared.CONCLUSION For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody(mAb)combination therapy,switching to a type II anti-CD20 mAb combination regimen may be considered.This approach may provide a new perspective in the treatment of MZL.

Bendamustine and rituximab as frontline therapy in extranodal marginal zone lymphoma:a single-institution experience

Extranodal marginal zone lymphoma(EMZL)encompasses 70%of cases of marginal zone lymphoma.Frontline bendamustine and rituximab(BR)were derived from trials involving other indolent non-Hodgkin’s lymphomas.Only one trial has evaluated frontline BR prospectively in EMZL.This retrospective study reports outcomes among EMZL patients receiving frontline BR.Twenty-five patients were included with a median age of 69 years(40–81).Five(20.0%)patients had stage Ⅰ/Ⅱ disease,and 20(80.0%)had stage Ⅲ/Ⅳ disease.The median number of cycles was 6.0(3.0–6.0).Maintenance rituximab was administered to 10(41.7%)individuals.Overall response rate(ORR)was 100.0%(60.0%complete response,40.0%partial response).Medians of overall survival and progression-free survival were not reached.The estimated 2-year progression-free survival was 85.2%and overall survival was 100.0%.Four(16.6%)patients had infections related to treatment;3(12.0%)transformed to diffuse large B-cell lymphoma;5(20.8%)had a relapse or progression of EMZL;and 3(12.0%)died unrelated to BR.BR is an efficacious and well-tolerated front-line regimen for EMZL with response data consistent with existing literature.

Sclerotic marginal zone lymphoma:A case report

BACKGROUND Marginal zone lymphoma(MZL)is an indolent non-Hodgkin B cell lymphoma with various architectural pattern including perifollicular,follicular colonization,nodular,micronodular,and diffuse patterns.A sclerotic variant has not been previously reported and represents a diagnostic pitfall.CASE SUMMARY A 66-year-old male developed left upper extremity swelling.Chest computed tomography(CT)in September 2020 showed 14 cm mass in left axilla.Needle core biopsy of axillary lymph node showed sclerotic tissue with atypical B lymphoid infiltrate but was non-diagnostic.Excisional biopsy was performed for diagnosis and showed extensive fibrosis and minor component of infiltrating B cells.Flow cytometry showed a small population of CD5-,CD10-,kappa restricted B cells.Monoclonal immunoglobulin heavy chain and light chain gene rearrangement were identified.Upon being diagnosed with MZL,patient was treated with rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone and achieved complete remission by positron emission tomography/CT.CONCLUSION This is an important case report because by morphology this case could have easily been overlooked as non-specific fibrosis with chronic inflammation representing a significant diagnostic pitfall.Moreover,this constitutes a new architectural pattern.While sclerotic lymphomas have rarely been described(often misdiagnosed as retroperitoneal fibrosis),we do not know of any cases describing this architectural presentation of MZL.

Secondary light chain amyloidosis with Waldenstr?m’s macroglobulinemia and intermodal marginal zone lymphoma:A case report

BACKGROUND The co-existence of Waldenstr?m’s macroglobulinemia(WM) with internodal marginal zone lymphoma(INMZL) is rare and often associated with poor prognosis.CASE SUMMARY We present a Chinese female patient who developed secondary light chain amyloidosis due to WM and INMZL and provides opinions on its systemic treatment.A 65-year-old woman was diagnosed with WM 6 years ago and received Bruton tyrosine kinase inhibitor monotherapy for two years.Her INMZL was confirmed due to left cervical lymphadenopathy.The patient presented with oedema in both lower limbs one year ago,and was diagnosed with secondary light chain amyloidosis.Treatment with the BC regimen(rituximab 375 mg/m~2 monthly for 6-8 courses,and bendamustine 90 mg/m~2 per day × 2,monthly for six courses) was initiated,but not tolerated due to toxic side effects.Bortezomibbased therapy was given for two months,including bortezomib,dexamethasone,and zanubrutinb.Oedema in both lower limbs was relieved and treatment efficacy was evaluated as partial remission.CONCLUSION A detailed clinical evaluation and active identification of the aetiology are recommended to avoid missed diagnosis and misdiagnosis.

Splenectomy with chemotherapy vs surgery alone as initial treatment for splenic marginal zone lymphoma

AIM： To evaluate the clinical characteristics of splenic marginal-zone lymphoma （SMZL） following antigen expression and the influence of therapeutic approaches on clinical outcome and overall survival （OS）.METHODS： A total of 30 patients with typical histological and immunohistochemical SMZL patterns were examined. Splenectomy plus chemotherapy was applied in 20 patients, while splenectomy as a single treatment-option was performed in 10 patients. Prognostic factor and overall survival rate were analyzed.RESULTS： Complete remission （CR） was achieved in 20 （66.7%）, partial remission （PR） in seven （23.3%）, and lethal outcome due to disease progression occurred in three （10.0%） patients. Median survival of patients with a splenectomy was 93.0 mo and for patients with splenectomy plus chemotherapy it was 207.5 mo （Log rank = 0.056, P 〉 0.05）. Time from onset of first symptoms to the beginning of the treatment （mean 9.4 too） was influenced by spleen dimensions, as measured by computerized tomography and ultra-sound （t = 2.558, P = 0.018）. Strong positivity （＋＋＋） of CD20 antigen expression in splenic tissue had a positive influence on OS （Log rank = 5.244, P 〈 0.05）. The analysis of factors interfering with survival （by the Kaplan-Meier method） revealed that gender, general symptoms, clinical stage, and spleen infiltration type （nodular vs diffuse） had no significant （P 〉 0.05） effects on the OS. The expression of other antigens （immunohistochemistry） also had no effect on survival-rate, as measured by a χ^2 test （P 〉 0.05）.CONCLUSION： Initial splenectomy combined with chemotherapy has been shown to be beneficial due to its advanced remission rate/duration; however, a larger controlled clinical study is required to confirm our findings.

Primary mucosal-associated lymphoid tissue extranodal marginal zone lymphoma of the bladder from an imaging perspective: A case report

BACKGROUND Mucosal-associated lymphoid tissue extranodal marginal zone(MALT)lymphoma is a low-grade tumor that rarely occurs in the urinary bladder.There is currently no consensus on the common imaging findings or most appropriate treatment in MALT lymphoma in the urinary bladder due to the limited number of reports.CASE SUMMARY A 48-year-old woman was admitted to the hospital with a 1-year history of macroscopic hematuria.Imaging showed a large homogeneous mass with an unclear boundary and an irregular morphology in the bladder.The mass had an abundant blood supply.For further diagnosis,transurethral cystoscopic biopsy and bone marrow biopsy was performed,and the patient was finally diagnosed with primary MALT lymphoma of the bladder.R-CHOP chemotherapy was carried out.After three cycles of chemotherapy,the mass disappeared and the bladder wall thickness was only 4 mm,which indicated excellent therapeutic response to the chemotherapy.To date,the patient remains asymptomatic and she visits our hospital regularly for the completion of the remaining chemotherapy cycles.CONCLUSION Primary MALT lymphoma of the bladder is rare,and there are certain characteristics in the ultrasonographic findings.Imaging findings play an important role in evaluating the therapeutic efficacy and are critical during long-term follow-up after therapy.

Follicular lymphoma presenting like marginal zone lymphoma:A case report

BACKGROUND Follicular lymphoma(FL),a common type of indolent lymphoma,carries markers of the germinal center,and the rearrangement of the BCL-2 gene is regarded as an initiating event and a hallmark of the neoplasm.When FL has marginal zone differentiation,some marginal zone features are carried by the neoplasm.CASE SUMMARY A 54-year-old male with lymphadenopathy,splenomegaly and hyperlymphocytosis was diagnosed with FL with marginal zone differentiation.The tumor demonstrated different features in the bone marrow(BM)compared with the follicle of the lymph node(LN).Some component of the neoplasm mimicked marginal zone lymphoma,such as infiltrating the marginal zone of the LN,displaying a monocytoid shape and lacking the expression of CD10 in the BM.The diagnosis of FL was made due to the concurrent detection of BCL-2 rearrangement in the LN and BM.CONCLUSION Discordant pathological features in LN and BM could mislead diagnosis.When clinical and pathological manifestations are confusing in diagnosis,typical genetic abnormalities are decisive.

Laparoscopic splenectomy for treatment of splenic marginal zone lymphoma

AIM: To investigate the short-term and long-term ef-ficacy and safety of laparoscopic splenectomy (LS) for treatment of splenic marginal zone lymphoma (SMZL). METHODS: A total of 18 continuous patients who were diagnosed with SMZL and underwent LS in our department from 2008 to 2012 were reviewed. The perioperative variables and long-term follow-up were evaluated. To evaluate the efficacy and safety of this procedure better, we also included 34 patients with liver cirrhosis who underwent LS, 49 patients with immune thrombocytopenia (ITP) who underwent LS, and 20 patients with SMZL who underwent open splenectomy (OS). The results observed in the different groups were compared.RESULTS: No differences were found in the sex and Child-Pugh class of the patients in SMZL-LS, SMZL-OS, ITP, and liver cirrhosis groups. The splenic length of the patients in the SMZL-LS group was similar to that in the SMZL-OS and liver cirrhosis groups but significantly longer than in the ITP group. The SMZL-LS group had a significantly longer operating time compared with the SMZL-OS, ITP, and liver cirrhosis groups, and the SMZL-LS group exhibited significantly less blood loss compared with the SMZL-OS group. No difference was found in the length of the postoperative hospital stay between the SMZL-LS, SMZL-OS, ITP, and liver cirrhosis-LS groups. After surgery, 6 (33.3%) SMZL-LS patients suffered slight complications. During mean fol-low-up periods of 13.6 and 12.8 mo, one patient from the SMZL-LS group and two from the SMZL-OS group died as a result of metastasis after surgery. None of the ITP and liver cirrhosis patients died. CONCLUSION: LS should be considered a feasible and safe procedure for treatment of SMZL in an effort to improve the treatment options and survival of patients.

Splenic Marginal Zone Lymphoma in a Patient with Positive Hepatitis B Virus Serology

We present a case in which an elderly woman diagnosed with a splenic marginal zone lymphoma (MZL) was found to have positive Hepatitis B serology. Link with Hepatitis C virus is well documented but reports of association of Hepatitis B virus (HBV) with splenic marginal zone lymphoma are still emerging. A 69-year-old lady presented with weight loss, pancytopenia and marked splenomegaly. Prior to commencing treatment, Hepatitis B serology confirmed Hepatitis B infection. She was treated with Chlorambucil along with anti-hepatitis B prophylaxis and HBV PCR monitoring. She had an excellent response to treatment with resolution of symptoms and splenomegaly. This case highlights the importance of testing for hepatitis B serology in patients diagnosed with splenic MZLs as causative agent. Although the association between HCV is well documented in the literature, a relationship between HBV may also be important. Also, chemotherapy +/- Rituximab for splenic MZL is associated with the reactivation of latent infections;hence providing prophylactic cover for pre-existing latent HBV infection may be required to prevent reactivation as in this case.

HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and open questions

There is plenty of data confirming that hepatitis C virus (HCV) infection is a predisposing factor for a B-cell non-Hodgkin's lymphoma (B-NHL) outbreak, while relatively few reports have addressed the role of HCV in affecting B-NHL patients' outcome. HCV infection may influence the short-term outcome of B-NHL because of the emergence of severe hepatic toxicity (HT) during immunochemotherapy. Furthermore, the long term outcome of HCV-related liver disease and patients' quality of life will possibly be affected by Rituximab maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic stem cell transplantation. In this review, data dealing with aggressive and low-grade B-NHL were separately analyzed. The few retrospective papers reporting on aggressive B-NHL patients showed that HCV infection is a risk factor for the outbreak of severe HT during treatment. This adverse event not infrequently leads to the reduction of treatment density and intensity. Existing papers report that low-grade B-NHL patients with HCV infection may have a more widespread disease, more frequent relapses or a lower ORR compared to HCV-negative patients. Notwithstanding, there is no statistical evidence that the prognosis of HCV-positive patients is inferior to that of HCV-negative subjects. HCV-positive prospective studies and longer follow-up are necessary to ascertain if HCV-positive B-NHL patients have inferior outcomes and if there are long term sequels of immunochemotherapies on the progression of liver disease.

Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma

The association of hepatitis C virus(HCV) and B-cell non-Hodgkin lymphomas(NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment(AT) with interferon(IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study(100 patients) the overall response rate(ORR) after first-line IFN-based AT was 77%(44% complete responses) and responses were sustainable(median duration of response 33 mo). These results were confirmed by a recent metaanalysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response(SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines' recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents(DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.

Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma:An up-to-date meta-analysis

BACKGROUND Gastric mucosa-associated lymphoid tissue(MALT)lymphoma(GML)is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori(H.pylori)-induced chronic gastritis.Clinical practice guidelines currently recommend H.pylori eradication as the preferred initial treatment for early-stage GML.To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML,an updated analysis and review of available evidence is imperative.AIM To perform a meta-analysis to assess the rate of complete remission(CR)of H.pylori-positive early-stage GML following bacterial eradication.METHODS We performed independent,computer-assisted literature searches using the PubMed/MEDLINE,Embase,and Cochrane Central databases through September 2022.Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H.pylori-positive patients.The risk of bias was assessed using Joanna Briggs Institute(JBI)Critical Appraisal Tools.The pooled estimate of the complete histopathological remission rate and respective confidence intervals(95%CI)were calculated following the random-effects model.Heterogeneity and inconsistency were assessed using Cochran’s Q test and I2 statistic,and heterogeneity was defined as P<0.01 and I²>50%,respectively.Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity.RESULTS The titles and abstracts of 1576 studies were screened;96 articles were retrieved and selected for full-text reading.Finally,61 studies were included in the proportional meta-analysis(P-MA).Forty-six were prospective and fifteen were retrospective uncontrolled,single-arm,observational studies.The overall risk of bias was low to moderate in all but a single report,with an average critical appraisal score across all studies of 79.02%.A total of 2936 H.pylori-positive early-stage GML patients,in whom H.pylori was successfully eradicated,were included in the analysis.The pooled CR of H.pylori-positive early-stage GML after bacterial eradication was 75.18%(95%CI:70.45%-79.91%).P-MA indicated the substantial heterogeneity in CR reported across studies(I2=92%;P<0.01).Meta-regression analysis identified statistically significant effect modifiers,including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study.CONCLUSION Comprehensive synthesis of available evidence suggests that H.pylori eradication is effective as the sole initial therapy for early-stage GML.Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR,the present study is a relevant to informing clinical practice.

Phase Ⅱ study of R-CVP followed by rituximab maintenance therapy for patients with advanced marginal zone lymphoma:consortium for improving survival of lymphoma(CISL)study

Background:The response rate and survival improvement for rituximab,a CD20-targeting monoclonal antibody,have been demonstrated in marginal zone lymphoma(MZL)as monotherapy and in combination with chemotherapeutic regimens,yet relapses still occur despite treatment completion.Thus,extending the period of remission in MZL patients remains an essential goal.This multicenter,single-arm,open-label phase II study evaluated the survival efficacy of 2 years of rituximab-maintenance therapy in patients with stage III-IV CD20-positive MZL who had responded to first-line R-CVP(rituximab,cyclophosphamide,vincristine,and prednisolone).The objective of this study was to determine whether rituximab maintenance following R-CVP warrants further investigation.Methods:Prior to rituximab-maintenance therapy,patients received 6-8 cycles of first-line R-CVP therapy for stage III-IV MZL.Rituximab(375 mg/m^(2)),cyclophosphamide(750 mg/m^(2)),and vincristine(1.4 mg/m^(2);maximum 2 mg)were administered via an intravenous infusion on day 1 of each 3-week cycle,while oral prednisolone(100 mg)was given on days 1-5 of each 3-week cycle.The patients who achieved complete response(CR),partial response(PR),or stable disease(SD)to R-CVP treatment,were prescribed rituximab-maintenance therapy which was administered intravenously at a dose of 375 mg/m^(2) every 8 weeks for up to 12 cycles.The primary endpoint was progression-free survival(PFS).Secondary endpoints were overall survival(OS)and treatment safety.Results:47 patients were enrolled,of whom,45(96%)received rituximab-maintenance treatment.Fifteen(33%)patients had nodal MZL.Following R-CVP first-line therapy,20(44%),22(49%),and 3(7%)patients achieved CR,PR,and SD,respectively.After a median follow-up of 38.2 months,their observed 3-year PFS rate was 81%.During the rituximab-maintenance,6 PR and 1 SD patients achieved CR following the administration of R-CVP.Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS(P=0.003)and demonstrated a 3-year OS rate of 90%.Rituximab-maintenance therapy was well tolerated,and the common treatment-emergent adverse events were sensory neuropathy(18%),myalgia(13%),fatigue(9%),and neutropenia(9%).Conclusion: Rituximab-maintenance therapy following first-line R-CVP demonstrated good PFS in patients with stage III-IV MZL, in addition to a favorable toxicity profile.

Gray zone lymphoma effectively treated with cyclophosphamide,doxorubicin,vincristine,prednisolone,and rituximab chemotherapy:A case report

BACKGROUND B-cell lymphoma,unclassifiable,with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma(BCLu-DLBCL/cHL),also referred to as gray zone lymphoma(GZL),is known to share features with cHL and DLBCL.However,GZL is often difficult to diagnose.There is no consensus regarding the optimal therapeutic regimen.Most reported cases of GZL have been in Caucasian and Hispanic individuals,and its incidence is lower in African-American and Asian populations,including the Japanese population.CASE SUMMARY A 69-year-old female presented at our hospital with a growing mass on the right side of her neck.An elastic,soft mass measuring 9 cm×6 cm was palpable in the right cervical region.Laboratory analyses showed pancytopenia,increased serum lactate dehydrogenase levels,and markedly increased levels of soluble interleukin-2 receptor.Enhanced computed tomography(CT)and fluorodeoxyglucose positron emission tomography(PET)/CT revealed multiple lesions throughout her body.She was diagnosed with GZL based on the characteristic pathological findings,the immunophenotype[CD20+,PAX5+,OCT2+/BOB1(focal+),CD30+,CD15-],and the strong positive expression of neoplastic programmed cell death protein ligand 1(PD-L1)in her lymphoma cells.The lymphoma was stage IV according to the Lugano classification and high-risk according to the International Prognostic Index for aggressive non-Hodgkin lymphoma.The patient received cyclophosphamide,doxorubicin,vincristine,prednisolone,and rituximab(R-CHOP)chemotherapy because the tumor cells were CD20+.She has remained in complete remission for 3 years.CONCLUSION GZL was diagnosed based on histopathology and immunophenotyping with ancillary PD-L1 positivity.R-CHOP chemotherapy was an effective treatment.

Role of non-Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma,trailing behind diffuse large B-cell lymphoma and follicular lymphoma.Gastric mucosa-associated lymphoid tissue lymphoma(GML)is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori(H.pylori)-induced chronic gastritis.On the other hand,a specific subset of individuals diagnosed with GML does not exhibit H.pylori infection.In contrast to its H.pylori-positive counterpart,it was previously believed that H.pylori-negative GML was less likely to respond to antimicrobial therapy.Despite this,surprisingly,increasing evidence supports that a considerable proportion of patients with H.pylori-negative GML show complete histopathological remission after bacterial eradication therapy.Nonetheless,the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended.In recent years,there has been growing interest in investigating the role of non-H.pylori gastric helicobacters(NHPHs)in the pathogenesis of H.pylori-negative GML.However,additional research is required to establish the causal relationship between NHPHs and GML.In this minireview,we examined the current understanding and proposed prospects on the involvement of NHPHs in H.pylori-negative GML,as well as their potential response to bacterial eradication therapy.

Endoscopic features of gastro-intestinal lymphomas: From diagnosis to follow-up

Many progresses have been done in the management of gastrointestinal(GI) lymphomas during last decades, especially after the discovery of Helicobacter pylori-dependent lymphoma development. The stepwise implementation of new endoscopic techniques, by means of echoendoscopy or double-balloon enteroscopy, enabled us to more precisely describe the endoscopic features of GI lymphomas with substantial contribution in patient management and in tailoring the treatment strategy with organ preserving approaches. In this review, we describe the recent progresses in GI lymphoma management from disease diagnosis to follow-up with a specific focus on the endoscopic presentation according to the involved site and the lymphoma subtype. Additionally, new or emerging endoscopic technologies that have an impact on the management of gastrointestinal lymphomas are reported. We here discuss the two most common subtypes of GI lymphomas: the mucosaassociated lymphoid tissue and the diffuse large B cell lymphoma. A general outline on the state-of-the-art of the disease and on the role of endoscopy in both diagnosis and follow-up will be performed.

Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue lymphomas

Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent extranodal marginal zone B-cell lymphoma, originating in acquired MALT that is induced in mucosal barriers as part of a normal adaptive immune response to a chronic immunoinflammatory stimulus, most notably chronic infection by Helicobacter pylori (H. pylori). This antigenic stimulation initially leads to lymphoid hyperplasia; the acquisition of additional genetic aberrations culminates in the activation of intracellular survival pathways, with disease progression due to proliferation and resistance to apoptosis, and the emergence of a malignant clone. There are descriptions of MALT lymphomas affecting practically every organ and system, with a marked geographic variability partially attributable to the epidemiology of the underlying risk factors; nevertheless, the digestive system (and predominantly the stomach) is the most frequently involved location, reflecting the gastrointestinal tract’s unique characteristics of contact with foreign antigens, high mucosal permeability, large extension and intrinsic lymphoid system. While early-stage gastric MALT lymphoma can frequently regress after the therapeutic reversal of the chronic immune stimulus through antibiotic eradication of H. pylori infection, the presence of immortalizing genetic abnormalities, of advanced disease or of eradication-refractoriness requires a more aggressive approach which is, presently, not consensual. The fact that MALT lymphomas are rare neoplasms, with a worldwide incidence of 1-1.5 cases per 105 population, per year, limits the ease of accrual of representative series of patients for robust clinical trials that could sustain informed evidence-based therapeutic decisions to optimize the quality of patient care.

Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment

The relationships between lymphomas and their microenvironment appear to follow 3 major patterns:(1)an independent pattern;(2)a dependent pattern on deregulated interactions;and(3)a dependent pattern on regulated coexistence.Typical examples of the third pattern are hepatitis C virus(HCV)-associated marginal zone lymphomas(MZLs)and mucosa-associated lymphoid tissue lymphomas.In these lymphomas,a regulated coexistence of the malignant cells and the microenvironmental factors usually occurs.At least initially,however,tumor development and cell growth largely depend on external signals from the microenvironment,such as viral antigens,cytokines,and cell-cell interactions.The association between HCV infection and B-cell lymphomas is not completely defined,although this association has been demonstrated by epidemiological studies.MZL and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV infection.Many mechanisms have been proposed for explaining HCV-induced lymphomagenesis;antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell lymphomas.Recently,antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent lymphomas.Importantly,clinically responses were linked to the eradication of the HCV-RNA,providing a strong argument in favor of a causative link between HCV and lymphoproliferation.

Management of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene

AIM To identify the clinical features of gastric mucosaassociated lymphoid tissue(MALT) lymphoma with extra copies of MALT1.METHODS This is a multi-centered,retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11;18) translocation. Patients were subdivided into patients without t(11;18) translocation or extra copies of MALT1(Group A,n = 88),patients with t(11;18) translocation(Group B,n = 27),and patients with extra copies of MALT1(Group C,n = 31). The clinical background,treatment,and outcomes of each group were investigated.RESULTS Groups A and C showed slight female predominance,whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A(69.3%),22 in Group B(81.5%),and 21 in Group C(67.7%). Helicobacter pylori(H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B,14 patients underwent radiotherapy alone,which resulted in lymphoma disappearance. Although the difference was not statistically significant,event-free survival in Group C tended to be inferior to that in Group A(P = 0.10).CONCLUSION Patients with t(11;18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication,similar to patients without t(11;18) translocation or extra copies of MALT1.