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{{Splenic marginal zone lymphoma}}
{{Splenic marginal zone lymphoma}}
{{CMG}}; {{AE}} {{AS}}
{{CMG}}; {{AE}} {{AS}}
{{SK}}: SMZL, Splenic B-cell marginal zone lymphoma, Splenic marginal zone B-cell lymphoma, Splenic lymphoma with circulating villous lymphocytes, Splenic lymphoma with lymphocytes, SLVL, Splenic MZL
{{SK}}: SMZL, Splenic B-cell marginal zone lymphoma, Splenic marginal zone B-cell lymphoma, Splenic lymphoma with circulating villous lymphocytes, Splenic lymphoma with lymphocytes, SLVL, Splenic MZL
==Overview==
==Overview==

Revision as of 01:04, 4 January 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [4]

Synonyms and keywords:: SMZL, Splenic B-cell marginal zone lymphoma, Splenic marginal zone B-cell lymphoma, Splenic lymphoma with circulating villous lymphocytes, Splenic lymphoma with lymphocytes, SLVL, Splenic MZL

Overview

Genes involved in the pathogenesis of splenic marginal zone lymphoma include immunoglobulin genes and CDK6 gene. On microscopic histopathological analysis, B-cells, villous lymphocytes, and sinus invasion are characteristic findings of splenic marginal zone lymphoma.

Pathophysiology

Pathogenesis

Genetics

  • Clonal rearrangements of the immunoglobulin genes (heavy and light chains) [1]
  • Most common chromosomal abnormality seen in splenic marginal zone lymphoma is the deletion of 7q region.[2]
  • Other abnormalities such as gain of function mutation in 3q, 4q, 5q, 9q, 12q, 20q and loss of function mutations in 7q and 17p have also been found.[3][4][5]
  • Most common genetic mutation is of NOTCH2 gene.[6][7]
  • Other genes involved with decreasing frequency are KLF2, CARD1, TRAF3, MYD88,TP53.[8][9][10][11][12]
  • Translocations of the CDK6 gene located at 7q21 have also been reported[13]
  • There are several pathways involved in the normal functioning of the cells. Genetic dysregulation may affect these pathways resulting in abnormal function.
  • Common genetic abnormalities and their affected pathways in splenic marginal zone lymphoma are summarized under:
Pathways Gene mutations

NFkB[14][15][9]

Apoptosis[16][17]

Cell communication[18][19][20]

Cell cycle control[5][17][20]

Lymphocyte development and regulation[18][15][20]

Chromosomal and transcriptional regulation[15][21]

Associated conditions

  • Hepatitis C infection
    • A strong association between splenic marginal zone lymphoma (SMZL) and hepatitis C infection has been observed in several studies indicating that viral antigen may be involved in the pathogenesis of the lymphoma.[22][23]
    • It is assumed that may be the HCV antigen stimulate the monoclonal B-cell proliferation through their specific receptor on the cell surface.[24][25]
    • Regression of the lymphoma was seen in patients after treatment with anti viral therapy again suggesting the role of viral antigen in its pathogenesis.[26]

Immunophenotype

Gross and Microscopic Pathology

  • Splenic marginal zone lymphoma (SMZL) is a subtype of non-hodgkin's lymphoma comprised of B-cells.[33]
  • It tends to involve spleen, bone marrow, liver and blood.[34]
  • The microscopic features of these organs are described below:
  • Spleen
    • Nodular pattern of lymphocytic infiltration of the white pulp involving both mantle ad marginal zone component.[27]
    • Biphasic distribution of B cell lymphocytes i.e small cells having dense chromatin and scant cytoplasm surrounded by intermediate size cells with interspersed blast cells.
    • Red pulp may also be involved either sparingly or diffusely penetrating the sinuses and cords.[35]
  • Bone Marrow:
    • Various patterns of Lymphocytic infiltration such as intrasinusoidal, nodular, interstitial and intravascular have been observed.[36]
    • Mixed pattern of lymphocytic infiltration with intrasinusoidal being predominant.[37][38]
    • Cell population consists of small, intermediate and large lymphoid cells but small cells having large nucleus with dense chromatin and scant cytoplasm are present in abundance.[39]
  • Lymph nodes
    • Splenic hilar and peripheral lymph nodes may be involved but less frequently as compared to the other organs.
    • Micronodular infiltration with no involvement of the sinuses.[40]


  • Blood

References

  1. [1] Dunn-Walters DK, Boursier L, Spencer J, Isaacson PG. "Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation." Hum Pathol. 1998 Jun;29(6):585-93. PMID: 9635678
  2. Boonstra R, Bosga-Bouwer A, van Imhoff GW, Krause V, Palmer M, Coupland RW, Dabbagh L, van den Berg E, van den Berg A, Poppema S (December 2003). "Splenic marginal zone lymphomas presenting with splenomegaly and typical immunophenotype are characterized by allelic loss in 7q31-32". Mod. Pathol. 16 (12): 1210–7. doi:10.1097/01.MP.0000095895.19756.77. PMID 14681321.
  3. Hernández JM, García JL, Gutiérrez NC, Mollejo M, Martínez-Climent JA, Flores T, González MB, Piris MA, San Miguel JF (May 2001). "Novel genomic imbalances in B-cell splenic marginal zone lymphomas revealed by comparative genomic hybridization and cytogenetics". Am. J. Pathol. 158 (5): 1843–50. doi:10.1016/S0002-9440(10)64140-5. PMC 1891967. PMID 11337382.
  4. Andersen CL, Gruszka-Westwood A, Atkinson S, Matutes E, Catovsky D, Pedersen RK, Pedersen BB, Pulczynski S, Hokland P, Jacobsen E, Koch J (January 2005). "Recurrent genomic imbalances in B-cell splenic marginal-zone lymphoma revealed by comparative genomic hybridization". Cancer Genet. Cytogenet. 156 (2): 122–8. doi:10.1016/j.cancergencyto.2004.04.026. PMID 15642391.
  5. 5.0 5.1 Salido M, Baró C, Oscier D, Stamatopoulos K, Dierlamm J, Matutes E, Traverse-Glehen A, Berger F, Felman P, Thieblemont C, Gesk S, Athanasiadou A, Davis Z, Gardiner A, Milla F, Ferrer A, Mollejo M, Calasanz MJ, Florensa L, Espinet B, Luño E, Wlodarska I, Verhoef G, García-Granero M, Salar A, Papadaki T, Serrano S, Piris MA, Solé F (September 2010). "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. 116 (9): 1479–88. doi:10.1182/blood-2010-02-267476. PMID 20479288.
  6. Rossi D, Trifonov V, Fangazio M, Bruscaggin A, Rasi S, Spina V, Monti S, Vaisitti T, Arruga F, Famà R, Ciardullo C, Greco M, Cresta S, Piranda D, Holmes A, Fabbri G, Messina M, Rinaldi A, Wang J, Agostinelli C, Piccaluga PP, Lucioni M, Tabbò F, Serra R, Franceschetti S, Deambrogi C, Daniele G, Gattei V, Marasca R, Facchetti F, Arcaini L, Inghirami G, Bertoni F, Pileri SA, Deaglio S, Foà R, Dalla-Favera R, Pasqualucci L, Rabadan R, Gaidano G (August 2012). "The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development". J. Exp. Med. 209 (9): 1537–51. doi:10.1084/jem.20120904. PMID 22891273.
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  13. [2] Corcoran MM, Mould SJ, Orchard JA, Ibbotson RE, Chapman RM, Boright AP, Platt C, Tsui LC, Scherer SW, Oscier DG. "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations." Oncogene. 1999 Nov 4;18(46):6271-7. PMID: 10597225
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