Transformed gastric mucosa-associated lymphoid tissue lymphoma originating in the colon and developing metachronously after Helicobacter pylori eradication:A case report

BACKGROUND Helicobacter pylori(H.pylori)eradication treatment for primary gastric mucosaassociated lymphoid tissue(MALT)lymphoma has already been established.However,t(11;18)(q21;q21)/API2-MALT1 translocation-positive lesions are a type of primary gastric MALT lymphoma in which a response to eradication treatment is difficult to achieve.In addition,trisomy 18 may be associated with diffuse large B-cell lymphoma(DLBCL)transformation of gastric MALT lymphoma.CASE SUMMARY A 66-year-old man was diagnosed with MALT lymphoma in the ascending colon by colonoscopy and biopsy.Two years later,esophagogastroduodenoscopy revealed chronic atrophic gastritis that was positive for H.pylori,and eradication treatment was administered.Two years and nine months later(at the age of 70),a new ulcerative lesion suggestive of MALT lymphoma appeared in the gastric body,and six months later,a similar lesion was also found in the fundus.One year later(4 years and 3 months after H.pylori eradication),at the age of 72,the lesion in the gastric body had become deeper and had propagated.A biopsy revealed a pathological diagnosis of DLBCL.Both MALT lymphoma lesions in the ascending colon and DLBCL lesions in the stomach were positive for the t(11;18)(q21;q21)/API2-MALT1 translocation,and trisomy 18q21 was also detected.After 6 courses of R-CHOP(rituximab,cyclophosphamide,doxorubicin,vincristine and prednisone)chemotherapy,all of the above lesions disappeared[complete remission(CR)],and CR has been maintained for more than 3 years.In addition,both the colonic and gastric lesions were proven to have the same clonality.CONCLUSION Because the patient had a MALT1 translocation with trisomy 18q21,it was thought that this gastric MALT lymphoma developed independently of H.pylori infection and progressed.

Rare incidence of mucosa-associated lymphoid tissue lymphoma presenting as buccal fat pad tumor:A case report

BACKGROUND Mucosa-associated lymphoid tissue(MALT)lymphoma,a type of non-Hodgkin lymphoma,originates in the mucosal lining of body organs and internal cavities,including the nose,mouth,lungs,and digestive tract.The lymphoma develops when the body produces abnormal B lymphocytes.These lymphomas develop at the edge of the lymphoid tissue,called the marginal zone,and,hence,are classified as a type of marginal zone lymphomas.They are the most common type of marginal zone lymphomas although their occurrence is rare.To date,no previous cases of MALT lymphoma in the buccal fat pad have been reported.CASE SUMMARY We report the case of a patient who presented with a mass on the frontal cheek.Magnetic resonance imaging revealed a tumor in the buccal fat pad,and histopathological and immunohistochemical findings confirmed the diagnosis of MALT lymphoma.The patient had a history of Helicobacter pylori and hepatitis C virus infection,suggesting an association between these infective agents and MALT lymphoma.CONCLUSION Consideration of MALT lymphoma is essential in the differential diagnosis of frontal cheek masses.

Early gastric composite tumor comprising signet-ring cell carcinoma and mucosa-associated lymphoid tissue lymphoma:A case report

BACKGROUND Composite tumors are neoplasms comprising two distinct,yet intermingling,cell populations.This paper reports a rare phenomenon where early gastric signet-ring cell carcinoma(SRCC)and gastric mucosa-associated lymphoid tissue(MALT)lymphoma coexist within the same lesion.CASE SUMMARY A 40-year-old woman presented to the West China Hospital for examination,which revealed a whitish,shallow,and uneven mucosal lesion in the stomach.The lesion was diagnosed as a poorly differentiated adenocarcinoma,including SRCC with atypical lymphoid hyperplasia associated with Helicobacter pylori infection,based on histopathological examination of the biopsy specimen.The lesion was excised using segmental gastrectomy.However,histological exami-nation of the surgical specimen confirmed that it was a poorly differentiated gastric adenocarcinoma with features of SRCC and MALT lymphoma.These two entities were stage I and coexisted in the same lesion.CONCLUSION It is uncommon for gastric SRCC and MALT lymphoma to coexist without distinct borders.Surgical resection is effective for these lesions.

Guiding function of positron emission tomographycomputed tomography examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma

AIM:To explore the role of positron emission tomographycomputed tomography(PET-CT)examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma(OAML).METHODS:The general clinical data,postoperative PET-CT results,treatment regimens,and the prognosis of 21 histopathologically confirmed OAML patients between October 2017 and September 2021 were collected.Among the 21 patients,five patients underwent surgical treatment alone,13 patients underwent surgical treatment combined with radiotherapy,and three patients underwent surgical treatment combined with chemotherapy.RESULTS:The follow-up period ranged from 8 to 79mo,with four cases of recurrence and no deaths.Through PETCT examination,two patients exhibited both local ocular metabolic elevation and systemic metastasis,and one of these patients had cervical lymph node metastasis,while the other had submandibular and parotid gland metastasis.Nine patients showed only local ocular metabolic elevation,while 10 patients had no abnormal metabolic activity locally.CONCLUSION:PET-CT examination plays a crucial role in detecting residual lesions and recurrence following tumor resection,aiding in precise disease staging,and facilitating the development of personalized treatment plans,ultimately improving patient prognosis.

Laterally spreading tumor-like primary rectal mucosa-associated lymphoid tissue lymphoma:A case report

BACKGROUND Colorectal mucosa-associated lymphoid tissue(MALT)lymphoma is a rare disease,and only a few cases have been reported to date.It has no specific clinical presentations and shows various endoscopic appearances.There is no uniform consensus on its treatment.With the advancement of endoscopic technology,endoscopic treatment has achieved better results in individual case reports of early-stage patients.CASE SUMMARY We report a case of rectal MALT in a 57-year-old Chinese man with no symptoms who received endoscopy as part of a routine physical examination,which incidentally found a 25 mm×20 mm,laterally spreading tumor(LST)-like elevated lesion in the rectum.Therefore,he was referred to our hospital for further endoscopic treatment.Complete and curable removal of the tumor was performed by endoscopic submucosal dissection.We observed enlarged and dilated branch-like vessels similar to those of gastric MALT lymphoma on magnifying endoscopy with narrow-band imaging.And immunopathological staining showed hyperplastic capillaries in the mucosa.Histopathological findings revealed diffusely hyperplastic lymphoid tissue in the lamina propria,with a visible lymphoid follicle structure surrounded by a large number of diffusely infiltrated lymphoid cells that had a relatively simple morphology and clear cytoplasm.In addition,immunohistochemical analysis suggested strongly positive expression for CD20 and Bcl-2.Gene rearrangement results showed positivity for IGH-A,IGH-C,IGK-B,and IGL.Taking all the above findings together,we arrived at a diagnosis of extranodal marginal zone B-cell lymphoma of MALT lymphoma. Positron emission tomography-computed tomographyexamination showed no other lesions involved. The patient will be followed byperiodic endoscopic observation.CONCLUSIONIn conclusion, we report a case of rectal MALT with an LST-like appearancetreated by endoscopic submucosal dissection. Further studies will be needed toexplore the clinical behavior, endoscopic appearance, and treatment of rectalMALT.

The immune modifying effects of amino acids on gut-associated lymphoid tissue

The intestine and the gut-associated lymphoid tissue（GALT） are essential components of whole body immune defense,protecting the body from foreign antigens and pathogens,while allowing tolerance to commensal bacteria and dietary antigens.The requirement for protein to support the immune system is well established.Less is known regarding the immune modifying properties of individual amino acids,particularly on the GALT.Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake,but the availability of specific dietary amino acids（in particular glutamine,glutamate,and arginine,and perhaps methionine,cysteine and threonine） are essential to optimizing the immune functions of the intestine and the proximal resident immune cells.These amino acids each have unique properties that include,maintaining the integrity,growth and function of the intestine,as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers,specific T cell functions,and the secretion of IgA by lamina propria cells.Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters.Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.

Low grade gastric mucosa associated lymphoid tissue lymphoma:Treatment strategies based on 10 year follow-up

AIM:To deduce strategic guidelines of gastric mucosa associated lymphoid tissue lymphoma (MALTOMA) by evaluating the long-term outcome of patients in respect to various treatment modalities. METHODS:A total of 55 patients with MALTOMA from May 1992 to August 2002 were retrospectively reviewed. RESULTS:Complete remission was obtained in 24 (82.8%) of 29 patients treated with anti Helicobacter pylori (Hpylori) regimen only.The duration to reach complete remission was 12 months (85 percentile,2-33 months).Five patients showed complete remission with radiation therapy (26-86 months).Two of them were Hpyloritreatment failure cases. CONCLUSION:Hpylorieradication is an effective primary treatment option for low grade MALTOMA and radiation therapy could be considered in patients with no evidence of Hpyloriinfection or who do not respond to Hpylorieradication therapy 12 months after successful eradication.

Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue lymphoma

Gastrointestinal lymphoma is the most common type of extranodal lymphoma,and most commonly affects the stomach.Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue(MALT)and diffuse large B-cell lymphoma are the most common histologic types of gastric lymphoma.Despite its increasing incidence,diagnosis of gastric lymphoma is difficult at an earlier stage due to its nonspecific symptoms and endoscopic findings,and,thus,a high index of suspicion,and multiple,deep,repeated biopsies at abnormally and normally appearing sites in the stomach are needed.In addition,testing for Helicobacter pylori(H.pylori)infection and endoscopic ultrasonography to determine the depth of tumor invasion and involvement of regional lymph nodes is essential for predicting response to H.pylori eradication and for assessment of disease progression.In addition,H.pylori infection and MALT lymphoma development are associated,and complete regression of low-grade MALT lymphomas after H.pylori eradication has been demonstrated.Radiotherapy and/or chemotherapy can be used in cases that show poor response to H.pylori eradication,negativity for H.pylori infection,or high-grade lymphoma.

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.

Gastric mucosa-associated lymphoid tissue lymphomas and Helicobacter pylori infection:A Colombian perspective

AIM： To assess the significance of chromosome translo- cation t（11;18）（q21;q21）, B-cell lymphoma 10 （BCL-10） protein and He/icobacter py/ori （H. py/on） infection in gastric mucosa-associated lymphoid tissue （MALT） lymphoma in Colombia.

Helicobacter pylori and gastric mucosa-associated lymphoid tissue lymphoma:Recent progress in pathogenesis and management

Recent progress in the research regarding the molecular pathogenesis and management of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is reviewed. In approximately 90% of cases, Helicobacter pylori (H. pylori) infection plays the causative role in the pathogenesis, and H. pylori eradication is nowadays the first-line treatment for this disease, which leads to complete disease remission in 50%-90% of cases. In H. pylori-dependent cases, microbe-generated immune responses, including interaction between B and T cells involving CD40 and CD40L co-stimulatory molecules, are considered to induce the development of MALT lymphoma. In H. pylori-independent cases, activation of the nuclear factor-κB pathway by oncogenic products of specific chromosomal translocations such as t(11;18)/API2-MALT1, or inactivation of tumor necrosis factor alpha-induced protein 3 (A20) are considered to contribute to the lymphomagenesis. Recently, a large-scale Japanese multicenter study confirmed that the long-term clinical outcome of gastric MALT lymphoma after H. pylori eradication is excellent. Treatment modalities for patients not responding to H. pylori eradication include a “watch and wait” strategy, radiotherapy, chemotherapy, rituximab immunotherapy, and a combination of these. Because of the indolent behavior of MALT lymphoma, second-line treatment should be tailored in consideration of the clinical stage and extent of the disease in each patient.

Primary thymic mucosa-associated lymphoid tissue lymphoma with multiple thin walled lung cysts: case report and literature review

Mucosa-associated lymphoid tissue （MALT） lymphoma of the thymus is rare. We reported a case of a 37-year-old Chinese female with Sjtgren＇s syndrome and hyperglobulinemia. She suffered from chronic cough for 3 weeks. Chest computed tomography （CT） demonstrated a multiloculated cystic mass in mediastinum prevascular space and multiple lung cysts. Laboratory exam of autoimmune markers showed positive of antinuclear antibody （ANA）, Sjtgren＇s syndrome A （SSA）, Sjtgren＇s syndrome B （SSB）, and rheumatoid factors （RF）. Thymectomy with lymph node dissection was performed. The pathology report revealed thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Under immunohistochemical stains, CD20 and Bcl-2 were positive. No evidence of recurrence of disease was found.

Primary mucosa-associated lymphoid tissue lymphoma of the liver: A report of two cases and review of the literature

Mucosa-associated lymphoid tissue(MALT) lymphoma of the liver is a very rare condition and thus the diag-nosis may be challeng-ing-. The clinical presentation is usually variable, rang-ing- from minimal clinical symptoms to severe end stag-e liver disease. In this paper, we describe the clinicopatholog-ic finding-s in two cases of primary hepatic MALT lymphoma. One case is an 80-year-old female with no underlying- chronic liver disease and the second case is a 30-year-old female with autoimmune hepatitis complicated by MALT lymphoma. In both specimens, there was diffuse infiltration of atypical B-lymphocytes that were positive for CD20 and CD79 a, but neg-ative for CD5, CD43 and CD10. There were occasional lymphoepithelial lesions involving- the hepatocytes or bile ducts. Polymerase chain reaction analysis showed monoclonal immunog-lobulin heavy chain g-ene rearrang-ement in both cases. The first case was treated with surg-ery but developed pulmonary recurrence a year after complete resection but went into remission following- treatment with rituximab. A second recurrence occurred in the rig-ht parotid g-land 7 years later, which was treated with idelalisib. The second case was effectively treated with rituximab. To our knowledg-e, the second case is the first reported case linked to autoimmune hepatitis.

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.

Remission of primary low-grade gastric lymphomas of the mucosa-associated lymphoid tissue type in immunocompromised pediatric patients

We report the remission of primary gastric lymphoma of the mucosa-associated lymphoid tissue （MALT） type in two immunocompromised pediatric patients. Patient 1, a 14-year-old boy in an immunocompromised state of unknown cause, complained of repeated abdominal pain. Examinations revealed gastric MALT with local invasion and lymph node involvement. Serum anti-Helicobacter pylori （H pylon） antibody was positive. H pylori eradication was abandoned due to its adverse effects. The MALT lesion spontaneously regressed over the next 24 months without any treatment for lymphoma. Patient 2, a 6-year-old boy, underwent cord blood transplantation for the treatment of adrenoleukodystrophy. He was administered immunosuppressants for graft-versus-host disease after transplantation. Nausea and hematochezia appeared and further examinations revealed gastric MALT with H pylori gastritis. Treatment consisting of medication for the Hpylori infection alone eradicated the Hpylori and completely resolved the patient＇s MALT lesion, as well. Patients i and 2 were followed up over periods of 10 years and 3 years, respectively, without any signs of relapse. In conclusion, gastric lymphoma of the MALT type can be cured by conservative treatment even in immunocompromised pediatric patients.

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.

Colonic adenocarcinoma,mucosa associated lymphoid tissue lymphoma and tuberculosis in a segment of colon:A case report

Synchronous occurrence of adenocarcinoma and mucosa associated lymphoid tissue(MALT) lymphoma of colon is rare,and its presence with coexisting tuberculosis is still rarer.To our knowledge,this may be the first case report.In the present report,we describe a 43-year-old female who presented with a history of abdominal pain,fever,loss of weight and loss of appetite.Colonoscopy showed a large ulceroproliferative mass arising from the caecum,biopsy of which showed it to be adenocarcinoma of the colon.A right hemicolectomy was performed and microscopic study of the colon revealed tuberculosis and synchronous adenocarcinoma with lymphoma.Eight of sixteen lymph nodes showed tuberculosis and three of sixteenpericoloniclymphnodes showed metastatic deposits.Immunostains further confirmed the tumour to be adenocarcinoma with MALT lymphoma.We would like to highlight the diagnostic challenges arising from the multi-faceted presentations of these three conditions.

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.

Colonic mucosa-associated lymphoid tissue lymphoma identified by chromoendoscopy

Colonic mucosa-associated lymphoid tissue (MALT) lymphomas are a rare occurrence and the definitive treatment has not been established. Solitary or multiple, elevated or polypoid lesions are the usual appearances of MALT lymphoma in the large intestine and sometimes the surface may reveal abnormal vascularity. Herein, we report a case of MALT lymphoma and review the relevant literature. Upon colonoscopy, a suspected pathologic lesion was observed in the proximal transverse colon. The lesion could be distinguished more prominently after using narrow-band imaging mode and indigo carmine-dye spraying chromoendoscopy. Histopathologic examination of this biopsy specimen revealed lymphoepithelial lesions with diffuse proliferation of atypical lymphoid cells effacing the glandular architecture and centrocyte-like cells infiltrating the lamina propria. Immunohistochemical analyses showed that tumor cells were positive for CD20 and Bcl-2e, and negative for CD10, CD23, and Bcl-6. According to Ann-Arbor staging system, the patient had stage IIE. A partial colectomy with dissection of the paracolic lymph nodes was performed. Until now, there is no recurrence of lymphoma at follow-up.

Impact of the microenvironment on the pathogenesis of mucosaassociated lymphoid tissue lymphomas

Approximately 8%of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue(MALT),also known as MALT lymphomas.These arise at a wide range of different extranodal sites,with most cases affecting the stomach,the lung,the ocular adnexa and the thyroid.The small intestine is involved in a lower percentage of cases.Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections(e.g.,Helicobacter pylori or Chlamydia psittaci infections)or autoimmune conditions(e.g.,Sjögren’s syndrome or Hashimoto thyroiditis).While these inflammatory processes trigger lymphoma cell proliferation and/or survival,they also shape the microenvironment.Thus,activated immune cells are actively recruited to the lymphoma,resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines.In addition,chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth.Recently,novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies.In this review,we aim to describe the composition of the microenvironment of MALT lymphoma,the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironmenttargeting agents.