Splenic marginal zone lymphoma: from genetics to management

Blood. 2016 Apr 28;127(17):2072-81. doi: 10.1182/blood-2015-11-624312. Epub 2016 Mar 17.


Splenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy involving the spleen, bone marrow, and frequently the blood. SMZL lymphomagenesis involves antigen and/or superantigen stimulation and molecular deregulation of genes (NOTCH2 and KLF2) involved in the physiological differentiation of spleen marginal zone B cells. Diagnosis requires either spleen histology or, alternatively, the documentation of a typical cell morphology and immunophenotype on blood cells coupled with the detection of intrasinusoidal infiltration by CD20(+) cells in the bone marrow. Among B-cell tumors, deletion of 7q and NOTCH2 mutations are almost specific lesions of SMZL, thus representing promising diagnostic biomarkers of this lymphoma. Although the majority of SMZLs show an indolent course with a median survival of approximately 10 years, nearly 30% of patients experience a poor outcome. No randomized trials are reported for SMZL, and few prospective trials are available. A watch-and-wait approach is advisable for asymptomatic patients. Treatment options for symptomatic patients ranges from splenectomy to rituximab alone or combined with chemotherapy. In some geographic areas, a subset of patients with SMZL associates with hepatitis C virus infection, prompting virus eradication as an effective lymphoma treatment. It would be worthwhile to explore deregulated cellular programs of SMZL as therapeutic targets in the future; improved clinical and biological prognostication will be essential for identifying patients who may benefit from novel approaches.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Antiviral Agents / therapeutic use
  • Autoimmune Diseases / etiology
  • Cell Transformation, Neoplastic / genetics
  • Combined Modality Therapy
  • Diagnosis, Differential
  • Disease Management
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Lymphoma, B-Cell, Marginal Zone / diagnosis
  • Lymphoma, B-Cell, Marginal Zone / drug therapy*
  • Lymphoma, B-Cell, Marginal Zone / epidemiology
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Mutation
  • Neoplasm Proteins / genetics*
  • Paraneoplastic Syndromes / etiology
  • Paraneoplastic Syndromes / immunology
  • Prognosis
  • Receptor, Notch2 / genetics*
  • Splenectomy
  • Splenic Neoplasms / diagnosis
  • Splenic Neoplasms / drug therapy*
  • Splenic Neoplasms / epidemiology
  • Splenic Neoplasms / genetics
  • Watchful Waiting


  • Antiviral Agents
  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • NOTCH2 protein, human
  • Neoplasm Proteins
  • Receptor, Notch2