• Anti-bacterial agents
• Mucosa-associated lymphoid tissue lymphoma
• NF-κB signal pathway
• Primary pulmonary lymphoma
• Rituximab

• Humans
• Lymphoma, B-Cell, Marginal Zone/diagnosis
• Lymphoma, B-Cell, Marginal Zone/pathology
• Lymphoma, B-Cell, Marginal Zone/therapy
• Lymphoma, B-Cell, Marginal Zone/epidemiology
• Lymphoma, B-Cell, Marginal Zone/diagnostic imaging
• Lung Neoplasms/diagnosis
• Lung Neoplasms/pathology
• Lung Neoplasms/therapy
• Lung Neoplasms/epidemiology
• Lung Neoplasms/diagnostic imaging
• Prognosis
• Tomography, X-Ray Computed

Extranodal marginal zone lymphoma (EMZL) is an indolent lymphoproliferative disease morphologically composed of small heterogeneous B lymphocytes. It generally occurs with a localized stage and can arise in various organs, the most frequent being the stomach, lung, and ocular adnexa. Depending on the presentation and the possible association with infectious agents, different therapeutic approaches are to be undertaken. The purpose of this review is to describe the biology underlying this pathology, the diagnostic, and therapeutic approach.

Extranodal Marginal Zone Lymphoma (EMZL lymphoma) is an indolent B-cell lymphoma with a median age at diagnosis of about 60 years. It accounts for 7–8% of all B-cell lymphomas. It can occur in various extranodal sites, including stomach, lung, ocular adnexa, and skin; furthermore, the disseminated disease can be found in 25–50% of cases. Several infectious agents, such as Helicobacter pylori (H. Pylori) in the case of gastric Mucosa Associated Lymphoid Tissue (MALT) Lymphoma, can drive the pathogenesis of this cancer, through the autoantigenic stimulation of T cells, but there may also be other factors participating such autoimmune diseases. Initial staging should include total body computed tomography, bone marrow aspirate, and endoscopic investigation if indicated. Fluorescence in situ hybridization (FISH), should be performed to detect the presence of specific chromosomal translocations involving the MALT1 and BCL10 genes, which leads to the activation of the NF-κB signaling pathway. Depending on the location and dissemination of the disease, different therapeutic choices may include targeted therapy against the etiopathogenetic agent, radiotherapy, immunochemotherapy, and biological drugs. The purpose of this review is to illustrate the complex biology and the diagnosis of this disease and to better define new treatment strategies.

• BALT
• MALT
• OAL
• diagnosis
• immunotherapy
• marginal zone lymphoma
• non-Hodgkin lymphoma
• prognosis
• targeted-therapy
• treatment

• Helicobacter pylori
• MALT
• bacteria
• immunomodulatory drugs
• lymphomagenesis
• macrolides
• negative
• spectrum

• NUTH 111-S0063 National Taiwan University Hospital

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 microenvironment-targeting agents.

• Mucosa-associated lymphoid tissue lymphoma
• Tumor microenvironment
• Microenvironment
• Helicobacter pylori
• Activated immune cells

Non-Hodgkin B-cell lymphomas (NHL) are a heterogeneous group of lymphoid neoplasms with complex etiopathology, rich symptomatology, and a variety of clinical courses, therefore requiring different therapeutic approaches. The hypothesis that an infectious agent may initiate chronic inflammation and facilitate B lymphocyte transformation and lymphogenesis has been raised in recent years. Viruses, like EBV, HTLV-1, HIV, HCV and parasites, like Plasmodium falciparum, have been linked to the development of lymphomas. The association of chronic Helicobacter pylori (H. pylori) infection with mucosa-associated lymphoid tissue (MALT) lymphoma, Borrelia burgdorferi with cutaneous MALT lymphoma and Chlamydophila psittaci with ocular adnexal MALT lymphoma is well documented. Recent studies have indicated that other infectious agents may also be relevant in B-cell lymphogenesis such as Coxiella burnettii, Campylobacter jejuni, Achromobacter xylosoxidans, and Escherichia coli. The aim of the present review is to provide a summary of the current literature on infectious bacterial agents associated with B-cell NHL and to discuss its role in lymphogenesis, taking into account the interaction between infectious agents, host factors, and the tumor environment.

• B-cell lymphoma
• Helicobacter pylori
• bacteria
• host factors
• lymphomagenesis
• tumor environment

• Bacterial Infections/complications
• Bacterial Infections/immunology
• Burkitt Lymphoma/complications
• Burkitt Lymphoma/microbiology
• Burkitt Lymphoma/pathology
• Carcinogenesis/genetics
• Carcinogenesis/immunology
• Carcinogenesis/metabolism
• Helicobacter Infections/complications
• Helicobacter Infections/microbiology
• Helicobacter pylori/pathogenicity
• Host-Pathogen Interactions/genetics
• Host-Pathogen Interactions/immunology
• Humans
• Lymphoma, B-Cell, Marginal Zone/complications
• Lymphoma, B-Cell, Marginal Zone/microbiology
• Lymphoma, B-Cell, Marginal Zone/pathology
• Lymphoma, Large B-Cell, Diffuse/complications
• Lymphoma, Large B-Cell, Diffuse/microbiology
• Lymphoma, Large B-Cell, Diffuse/pathology
• Tumor Microenvironment/genetics
• Tumor Microenvironment/immunology

The group of B-cell lymphomas primarily involving the lung encompasses different histological entities with distinct biological aspects, while sharing some clinical and radiological features related to their common anatomic site of occurrence. Recent molecular advances in the molecular genetics of these lesions have substantially improved of our understanding of the mechanisms of lymphomagenesis, adding novel information to histology in order to better characterize and manage these diseases. This review summarizes the available clinical, radiological, pathological, and molecular data on primary pulmonary B-cell lymphomas, discusses the mechanisms of lymphomagenesis, and highlights the role of a multi-disciplinary management in overcoming the diagnostic and therapeutic challenges in this setting.

Primary pulmonary B-cell lymphomas (PP-BCLs) comprise a group of extranodal non-Hodgkin lymphomas of B-cell origin, which primarily affect the lung without evidence of extrapulmonary disease at the time of diagnosis and up to 3 months afterwards. Primary lymphoid proliferations of the lung are most often of B-cell lineage, and include three major entities with different clinical, morphological, and molecular features: primary pulmonary marginal zone lymphoma of mucosa-associated lymphoid tissue (PP-MZL, or MALT lymphoma), primary pulmonary diffuse large B cell lymphoma (PP-DLBCL), and lymphomatoid granulomatosis (LYG). Less common entities include primary effusion B-cell lymphoma (PEL) and intravascular large B cell lymphoma (IVLBCL). A proper workup requires a multidisciplinary approach, including radiologists, pneumologists, thoracic surgeons, pathologists, hemato-oncologists, and radiation oncologists, in order to achieve a correct diagnosis and risk assessment. Aim of this review is to analyze and outline the clinical and pathological features of the most frequent PP-BCLs, and to critically analyze the major issues in their diagnosis and management.

• BALT
• MALT lymphoma
• diffuse large B-cell lymphoma
• intravascular large B-cell lymphoma
• lymphomatoid granulomatosis
• primary effusion lymphoma
• pulmonary B-cell lymphoma

Primary pulmonary mucosa‐associated lymphoid tissue‐derived (MALT) lymphoma is a rare disease with a favorable prognosis. However, its clinical characteristics, diagnosis, treatment, and prognoses remain unclear. We retrospectively analyzed 80 patients with pathologically confirmed MALT lymphoma from 2006 to 2018. The clinical characteristics, diagnosis, treatments, and prognoses of all the 80 patients were recorded. Patients were stratified into surgery and biopsy groups, respectively, to evaluate the role of surgery in the diagnosis and treatment of MALT lymphoma. The prognoses were compared between different clinical characteristics and treatments. Pathological diagnoses were confirmed by surgery, bronchoscopy, and percutaneous biopsy. Thirty patients were treated by surgery. While MALT lymphoma was only diagnosed by bronchofiberoscopy or bercutaneous biopsy in four of 18 patients in the surgery group who underwent the procedure. Six patients received adjuvant chemotherapy and one patient received involved‐field radiotherapy in surgery group. Thirty‐one patients were treated with chemotherapy alone, one patient was treated with radiotherapy, one patient received only symptomatic and supportive treatment, and waiting and watching without treatment were recommended in 17 patients in biopsy group. Eight patients died during follow‐up and the 5‐year survival rate was 87.1%. Tumor number, treatment, and age were prognostic factors for overall survival (OS), but age was the only independent prognostic factor according to multivariate analysis. While, tumor number was the only prognostic factor in the analysis about progression‐free survival (PFS). No significant difference was found in OS or PFS between patients treated with and without surgical resection. MALT lymphoma is an indolent disease with favorable treatment outcome. Tumor number is associated with PFS and age is the only significant prognostic factor for pulmonary MALT lymphoma patients because of its indolent nature, but surgery still plays an important role in the diagnosis and treatment of MALT lymphoma.

• MALT lymphoma
• chemotherapy
• prognosis
• pulmonary lymphoma
• thoracic surgery