Epidemiology, diagnosis, and treatment of primary pulmonary mucosa-associated lymphoid tissue lymphoma

Primary pulmonary B-cell lymphomas are rare, accounting for <1% of non-Hodgkin lymphomas (NHLs) and 3–4% of extranodal NHL. Extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT; pulmonary MALT lymphoma), arising from bronchus-associated lymphoid tissue (BALT), represents over 80–90% of cases. These tumors typically develop as a result of chronic antigenic stimulation in the setting of persistent inflammation, due to infection, or autoimmune disease. Two main pathogenetic phases are recognized in their development: an antigen-dependent phase, in which clonal B-cell expansion and survival are driven by ongoing exposure to specific antigens, and an antigen-independent phase, in which B-cell proliferation becomes autonomous due to cytogenetic and molecular alterations. Clinically, pulmonary MALT lymphoma has an indolent course and is often detected incidentally; when symptoms occur, they are non-specific. Radiologic findings include consolidations, nodules, or masses. Diagnosis relies on histopathology, immunophenotyping (CD20⁺, light-chain restriction, CD5⁻/CD10⁻/cyclin D1⁻), and molecular studies. Most patients present at early Ann Arbor stages, with a 5-year overall survival exceeding 90%. Management should be tailored to the disease stage, symptoms, comorbidities, and patient preferences. A watch-and-wait approach is appropriate for asymptomatic patients without treatment indications. Radiotherapy is highly effective for localized disease, while rituximab alone or with chemotherapy, particularly bendamustine-rituximab, is preferred for advanced symptomatic disease. Bruton’s tyrosine kinase inhibitors have shown efficacy in relapsed or refractory cases. This review summarizes the epidemiology, pathogenesis, clinicopathologic features, diagnosis, and evolving treatment strategies of pulmonary MALT lymphoma, highlighting its favorable prognosis and unique immunobiological origin.