Clinical manifestations, pathologic features, and diagnosis of splenic marginal zone lymphoma
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- Jon C Aster, MD
Jon C Aster, MD
- Professor of Pathology
- Harvard Medical School
The non-Hodgkin lymphoma subtype marginal zone lymphoma encompasses three distinct diseases that have been historically classified together because they appear to arise from post-germinal center marginal zone B cells and share a similar immunophenotype: positive for B cell markers CD19, CD20, and CD22, and negative for CD5, CD10, and usually CD23 [1-4].
The three diseases in this category that are recognized in the 2016 WHO classification system of lymphoid neoplasms include:
●Splenic marginal zone B cell lymphoma (± villous lymphocytes)
●Extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT) type (MALT-type lymphoma, MALT lymphoma)
●Nodal marginal zone B cell lymphomaTo continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994; 84:1361.
- Harris NL, Jaffe ES, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17:3835.
- World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008.
- Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
- Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol 1998; 16:2780.
- Liu L, Wang H, Chen Y, et al. Splenic marginal zone lymphoma: a population-based study on the 2001-2008 incidence and survival in the United States. Leuk Lymphoma 2013; 54:1380.
- Isaacson PG, Matutes E, Burke M, Catovsky D. The histopathology of splenic lymphoma with villous lymphocytes. Blood 1994; 84:3828.
- Mollejo M, Menárguez J, Lloret E, et al. Splenic marginal zone lymphoma: a distinctive type of low-grade B-cell lymphoma. A clinicopathological study of 13 cases. Am J Surg Pathol 1995; 19:1146.
- Pittaluga S, Verhoef G, Criel A, et al. "Small" B-cell non-Hodgkin's lymphomas with splenomegaly at presentation are either mantle cell lymphoma or marginal zone cell lymphoma. A study based on histology, cytology, immunohistochemistry, and cytogenetic analysis. Am J Surg Pathol 1996; 20:211.
- Arber DA, Rappaport H, Weiss LM. Non-Hodgkin's lymphoproliferative disorders involving the spleen. Mod Pathol 1997; 10:18.
- Audouin J, Le Tourneau A, Molina T, et al. Patterns of bone marrow involvement in 58 patients presenting primary splenic marginal zone lymphoma with or without circulating villous lymphocytes. Br J Haematol 2003; 122:404.
- Ruiz-Ballesteros E, Mollejo M, Rodriguez A, et al. Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis. Blood 2005; 106:1831.
- Rossi D, Trifonov V, Fangazio M, et al. The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development. J Exp Med 2012; 209:1537.
- Kiel MJ, Velusamy T, Betz BL, et al. Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J Exp Med 2012; 209:1553.
- Hermine O, Lefrère F, Bronowicki JP, et al. Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 2002; 347:89.
- Benavente Y, Mbisa G, Labo N, et al. Antibodies against lytic and latent Kaposi's sarcoma-associated herpes virus antigens and lymphoma in the European EpiLymph case-control study. Br J Cancer 2011; 105:1768.
- Iannitto E, Ambrosetti A, Ammatuna E, et al. Splenic marginal zone lymphoma with or without villous lymphocytes. Hematologic findings and outcomes in a series of 57 patients. Cancer 2004; 101:2050.
- Franco V, Florena AM, Iannitto E. Splenic marginal zone lymphoma. Blood 2003; 101:2464.
- Matutes E, Oscier D, Montalban C, et al. Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria. Leukemia 2008; 22:487.
- Melo JV, Hegde U, Parreira A, et al. Splenic B cell lymphoma with circulating villous lymphocytes: differential diagnosis of B cell leukaemias with large spleens. J Clin Pathol 1987; 40:642.
- Chacón JI, Mollejo M, Muñoz E, et al. Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 60 patients. Blood 2002; 100:1648.
- Zignego AL, Giannini C, Monti M, Gragnani L. Hepatitis C virus lymphotropism: lessons from a decade of studies. Dig Liver Dis 2007; 39 Suppl 1:S38.
- Schreiber AD, Zweiman B, Atkins P, et al. Acquired angioedema with lymphoproliferative disorder: association of C1 inhibitor deficiency with cellular abnormality. Blood 1976; 48:567.
- Bain BJ, Catovsky D, Ewan PW. Acquired angioedema as the presenting feature of lymphoproliferative disorders of mature B-lymphocytes. Cancer 1993; 72:3318.
- Phanish MK, Owen A, Parry DH. Spontaneous regression of acquired C1 esterase inhibitor deficiency associated with splenic marginal zone lymphoma presenting with recurrent angio-oedema. J Clin Pathol 2002; 55:789.
- Delsol G, Diebold J, Isaacson PG, et al. Pathology of the spleen: report on the workshop of the VIIIth meeting of the European Association for Haematopathology, Paris 1996. Histopathology 1998; 32:172.
- Schmid C, Kirkham N, Diss T, Isaacson PG. Splenic marginal zone cell lymphoma. Am J Surg Pathol 1992; 16:455.
- Mollejo M, Lloret E, Menárguez J, et al. Lymph node involvement by splenic marginal zone lymphoma: morphological and immunohistochemical features. Am J Surg Pathol 1997; 21:772.
- Matutes E, Morilla R, Owusu-Ankomah K, et al. The immunophenotype of splenic lymphoma with villous lymphocytes and its relevance to the differential diagnosis with other B-cell disorders. Blood 1994; 83:1558.
- Savilo E, Campo E, Mollejo M, et al. Absence of cyclin D1 protein expression in splenic marginal zone lymphoma. Mod Pathol 1998; 11:601.
- Salido M, Baró C, Oscier D, et al. Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group. Blood 2010; 116:1479.
- Rinaldi A, Forconi F, Arcaini L, et al. Immunogenetics features and genomic lesions in splenic marginal zone lymphoma. Br J Haematol 2010; 151:435.
- Rinaldi A, Mian M, Chigrinova E, et al. Genome-wide DNA profiling of marginal zone lymphomas identifies subtype-specific lesions with an impact on the clinical outcome. Blood 2011; 117:1595.
- Zhu D, Oscier DG, Stevenson FK. Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes. Blood 1995; 85:1603.
- Algara P, Mateo MS, Sanchez-Beato M, et al. Analysis of the IgV(H) somatic mutations in splenic marginal zone lymphoma defines a group of unmutated cases with frequent 7q deletion and adverse clinical course. Blood 2002; 99:1299.
- Dunn-Walters DK, Boursier L, Spencer J, Isaacson PG. Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation. Hum Pathol 1998; 29:585.
- Oscier DG, Matutes E, Gardiner A, et al. Cytogenetic studies in splenic lymphoma with villous lymphocytes. Br J Haematol 1993; 85:487.
- Jadayel D, Matutes E, Dyer MJ, et al. Splenic lymphoma with villous lymphocytes: analysis of BCL-1 rearrangements and expression of the cyclin D1 gene. Blood 1994; 83:3664.
- Gruszka-Westwood AM, Matutes E, Coignet LJ, et al. The incidence of trisomy 3 in splenic lymphoma with villous lymphocytes: a study by FISH. Br J Haematol 1999; 104:600.
- Thieblemont C, Felman P, Callet-Bauchu E, et al. Splenic marginal-zone lymphoma: a distinct clinical and pathological entity. Lancet Oncol 2003; 4:95.
- Wotherspoon AC, Finn TM, Isaacson PG. Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. Blood 1995; 85:2000.
- Brynes RK, Almaguer PD, Leathery KE, et al. Numerical cytogenetic abnormalities of chromosomes 3, 7, and 12 in marginal zone B-cell lymphomas. Mod Pathol 1996; 9:995.
- Dufresne SD, Felgar RE, Sargent RL, et al. Defining the borders of splenic marginal zone lymphoma: a multiparameter study. Hum Pathol 2010; 41:540.
- Martínez N, Almaraz C, Vaqué JP, et al. Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation. Leukemia 2014; 28:1334.
- Parry M, Rose-Zerilli MJ, Gibson J, et al. Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma. PLoS One 2013; 8:e83244.
- Xochelli A, Kalpadakis C, Gardiner A, et al. Clonal B-cell lymphocytosis exhibiting immunophenotypic features consistent with a marginal-zone origin: is this a distinct entity? Blood 2014; 123:1199.
- Parry-Jones N, Matutes E, Gruszka-Westwood AM, et al. Prognostic features of splenic lymphoma with villous lymphocytes: a report on 129 patients. Br J Haematol 2003; 120:759.
- Olszewski AJ, Castillo JJ. Survival of patients with marginal zone lymphoma: analysis of the Surveillance, Epidemiology, and End Results database. Cancer 2013; 119:629.
- Arcaini L, Lazzarino M, Colombo N, et al. Splenic marginal zone lymphoma: a prognostic model for clinical use. Blood 2006; 107:4643.
- Montalbán C, Abraira V, Arcaini L, et al. Risk stratification for Splenic Marginal Zone Lymphoma based on haemoglobin concentration, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy: development and validation on 593 cases. Br J Haematol 2012; 159:164.
- Gruszka-Westwood AM, Hamoudi RA, Matutes E, et al. p53 abnormalities in splenic lymphoma with villous lymphocytes. Blood 2001; 97:3552.
- Dungarwalla M, Appiah-Cubi S, Kulkarni S, et al. High-grade transformation in splenic marginal zone lymphoma with circulating villous lymphocytes: the site of transformation influences response to therapy and prognosis. Br J Haematol 2008; 143:71.
- CLINICAL FEATURES
- PATHOLOGIC FEATURES
- - Peripheral blood
- - Spleen
- - Lymph nodes
- - Bone marrow
- Genetic features
- DIFFERENTIAL DIAGNOSIS
- Follicular lymphoma
- Mantle cell lymphoma
- Chronic lymphocytic leukemia
- Hairy cell leukemia
- Lymphoplasmacytic lymphoma (Waldenström macroglobulinemia)
- MALT lymphoma
- Splenic B cell lymphoma/leukemia, unclassifiable
- Monoclonal B cell lymphocytosis