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Splenic Marginal Zone Lymphoma (SMZL) is a rare, indolent B-cell non-Hodgkin lymphoma originating in the spleen’s marginal zone, accounting for 1-2% of NHLs and 20% of splenic lymphomas. It involves abnormal B-cells accumulating in the spleen, bone marrow, and blood, often with villous lymphocytes. In 2025, ~1,000 US cases annually, median age 65, more in women, associated with hepatitis C in 20-30%.
Symptoms include abdominal fullness/pain (splenomegaly in 80%), fatigue, weight loss, night sweats, recurrent infections (from cytopenias), easy bruising (thrombocytopenia), and anemia symptoms (pallor, shortness of breath). Lymphadenopathy is rare. Symptoms are insidious, progressing over years.
Causes involve chronic antigenic stimulation, with hepatitis C (HCV) linked in 15-30% (antiviral therapy induces remission). Genetic mutations (NOTCH2, TP53) and immune dysregulation are key. Risk factors include age, female gender, and autoimmune diseases. In 2025, microbiome and epigenetics are explored.
Diagnosis uses CBC showing cytopenias/lymphocytosis, blood smear for villous lymphocytes, bone marrow biopsy (nodular infiltrate), and splenectomy for confirmation. Flow cytometry (CD20+, CD5-/CD10-), cytogenetics (del(7q)). Imaging (CT, PET) assesses spleen. In 2025, NGS identifies mutations.
Watch and wait for asymptomatic; splenectomy (historical standard, 70% remission) or rituximab (90% response, preferred). Chemoimmunotherapy (R-bendamustine) for progressive. Antivirals for HCV+. In 2025, BTK inhibitors (ibrutinib) show 60% response in relapsed.
In 2025, 10-year survival is 70-80%, with indolent course. Targeted therapies improve transformation-free survival. By 2030, novel inhibitors could achieve 90% survival.
The information for SMZL is sourced from Mayo Clinic’s “Splenic marginal zone lymphoma – Symptoms and causes” for symptoms; Cleveland Clinic’s “Splenic Marginal Zone Lymphoma” for treatment; NCI’s “Splenic Marginal Zone Lymphoma Treatment” for diagnosis; Healthline’s “Splenic Marginal Zone Lymphoma: Symptoms, Causes, Treatment” for overview; and PMC’s “Advances in SMZL Therapy” for future outlook.
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