Non-gastric mucosa-associated lymphoid tissue lymphomas: a narrative review of pathogenesis, diagnosis, and treatment strategies.

Abstract

<h4>Background and objective</h4>Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) are indolent non-Hodgkin lymphomas (NHLs) that can arise in various extranodal organs, often due to chronic inflammation. Gastric MALT lymphomas are well characterized; however, MALT lymphomas may occur in diverse sites such as the ocular adnexa, salivary glands, thyroid, lung, skin, and the small intestine. These site-specific MALT lymphomas have distinct etiologic associations, clinical presentation, and management considerations. This review provides an updated, site-specific overview to guide the diagnostic and therapeutic approach to non-gastric MALT lymphoma in adults.<h4>Methods</h4>We reviewed peer-reviewed articles [2015-2025] on non-gastric MALT lymphomas, focusing on pathophysiology/etiology, diagnostic workup, and treatment strategies for each site. Key sources include recent reviews and guidelines from high-impact journals.<h4>Key content and findings</h4>Chronic antigenic stimulation is a unifying theme in MALT lymphoma genesis, either through infectious etiologies or autoimmune conditions. Ocular adnexal MALT lymphoma (OAML) is linked to <i>Chlamydia psittaci</i> (<i>C. psittaci</i>) infection in certain regions; salivary MALT lymphoma is related to Sjogren's syndrome (SS); thyroid MALT lymphoma develops in the background of Hashimoto's thyroiditis; pulmonary MALT lymphoma can be linked to chronic airway inflammation due to <i>Achromobacter xylosoxidans</i> (<i>A. xylosoxidans</i>); small intestinal MALT lymphoma can be associated with <i>Campylobacter jejuni</i> (<i>C. jejuni</i>) infection; and cutaneous MALT lymphoma can be linked to <i>Borrelia burgdorferi</i> (<i>B. burgdorferi</i>) infection. Diagnostic evaluation requires adequate tissue biopsy for histopathology and immunohistochemistry. MALT lymphomas exhibit an immunophenotype consistent with CD20⁺, CD79a⁺, IgM⁺ with light chain restriction, BCL2⁺, and negative for CD5, CD10, and cyclin D1. Staging for OAML and cutaneous lymphomas is tumor-node-metastasis (TNM)-based, while the others utilize an Ann Arbor staging system. Computed tomography (CT)/magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT are used to determine the staging and spread of tumors. Treatments are not standardized but consist of therapy with radiotherapy and surgical excision for localized disease, and chemotherapy/for disseminated disease. Intestinal MALT lymphoma differs, as first-line treatment consists of antibiotics and then chemotherapy/immunotherapy.<h4>Conclusions</h4>The non-gastric MALT lymphomas have an excellent prognosis as a whole; relapses are common but manageable, and disseminated disease is rare. Long-term follow-up is recommended in all cases.