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 lymphoma
- 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