Splenic marginal zone lymphoma pathophysiology: Difference between revisions

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===Pathogenesis===
===Pathogenesis===
===Genetics===
===Genetics===
Genes involved in the pathogenesis of splenic marginal zone lymphoma include:
* 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:
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! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|'''Pathways'''}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|'''Genes Involved'''}}
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NFkB<ref name="pmid25428260">{{cite journal |vauthors=Clipson A, Wang M, de Leval L, Ashton-Key M, Wotherspoon A, Vassiliou G, Bolli N, Grove C, Moody S, Escudero-Ibarz L, Gundem G, Brugger K, Xue X, Mi E, Bench A, Scott M, Liu H, Follows G, Robles EF, Martinez-Climent JA, Oscier D, Watkins AJ, Du MQ |title=KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype |journal=Leukemia |volume=29 |issue=5 |pages=1177–85 |date=May 2015 |pmid=25428260 |doi=10.1038/leu.2014.330 |url=}}</ref><ref name="pmid25779943">{{cite journal |vauthors=Parry M, Rose-Zerilli MJ, Ljungström V, Gibson J, Wang J, Walewska R, Parker H, Parker A, Davis Z, Gardiner A, McIver-Brown N, Kalpadakis C, Xochelli A, Anagnostopoulos A, Fazi C, de Castro DG, Dearden C, Pratt G, Rosenquist R, Ashton-Key M, Forconi F, Collins A, Ghia P, Matutes E, Pangalis G, Stamatopoulos K, Oscier D, Strefford JC |title=Genetics and Prognostication in Splenic Marginal Zone Lymphoma: Revelations from Deep Sequencing |journal=Clin. Cancer Res. |volume=21 |issue=18 |pages=4174–4183 |date=September 2015 |pmid=25779943 |pmc=4490180 |doi=10.1158/1078-0432.CCR-14-2759 |url=}}</ref>
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KLF2, TNFAIP3, MYD88, TRAF3, CARD11, MLL2, BTK, REL, SYK
|-
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[[Apoptosis]]<ref name="pmid15914563">{{cite journal |vauthors=Ruiz-Ballesteros E, Mollejo M, Rodriguez A, Camacho FI, Algara P, Martinez N, Pollán M, Sanchez-Aguilera A, Menarguez J, Campo E, Martinez P, Mateo M, Piris MA |title=Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis |journal=Blood |volume=106 |issue=5 |pages=1831–8 |date=September 2005 |pmid=15914563 |doi=10.1182/blood-2004-10-3898 |url=}}</ref><ref name="pmid15507668">{{cite journal |vauthors=Trøen G, Nygaard V, Jenssen TK, Ikonomou IM, Tierens A, Matutes E, Gruszka-Westwood A, Catovsky D, Myklebost O, Lauritzsen G, Hovig E, Delabie J |title=Constitutive expression of the AP-1 transcription factors c-jun, junD, junB, and c-fos and the marginal zone B-cell transcription factor Notch2 in splenic marginal zone lymphoma |journal=J Mol Diagn |volume=6 |issue=4 |pages=297–307 |date=November 2004 |pmid=15507668 |pmc=1867488 |doi=10.1016/S1525-1578(10)60525-9 |url=}}</ref>
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BIRC3, TNFRSF5, TRAF3, TRAF5, BTK, XPB, APAF-1, IRF5, REL, PKCA,TMEM209
|-
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Cell communication<ref name="pmid24349473">{{cite journal |vauthors=Parry M, Rose-Zerilli MJ, Gibson J, Ennis S, Walewska R, Forster J, Parker H, Davis Z, Gardiner A, Collins A, Oscier DG, Strefford JC |title=Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma |journal=PLoS ONE |volume=8 |issue=12 |pages=e83244 |date=2013 |pmid=24349473 |pmc=3862727 |doi=10.1371/journal.pone.0083244 |url=}}</ref><ref name="pmid22816737">{{cite journal |vauthors=Fresquet V, Robles EF, Parker A, Martinez-Useros J, Mena M, Malumbres R, Agirre X, Catarino S, Arteta D, Osaba L, Mollejo M, Hernandez-Rivas JM, Calasanz MJ, Daibata M, Dyer MJ, Prosper F, Vizcarra E, Piris MÁ, Oscier D, Martinez-Climent JA |title=High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma |journal=Br. J. Haematol. |volume=158 |issue=6 |pages=712–26 |date=September 2012 |pmid=22816737 |doi=10.1111/j.1365-2141.2012.09226.x |url=}}</ref><ref name="pmid24296945">{{cite journal |vauthors=Martínez N, Almaraz C, Vaqué JP, Varela I, Derdak S, Beltran S, Mollejo M, Campos-Martin Y, Agueda L, Rinaldi A, Kwee I, Gut M, Blanc J, Oscier D, Strefford JC, Martinez-Lopez J, Salar A, Sole F, Rodriguez-Peralto JL, Diez-Tascón C, García JF, Fraga M, Sebastián E, Alvés J, Menárguez J, González-Carreró J, Casado LF, Bayes M, Bertoni F, Gut I, Piris MA |title=Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation |journal=Leukemia |volume=28 |issue=6 |pages=1334–40 |date=June 2014 |pmid=24296945 |doi=10.1038/leu.2013.365 |url=}}</ref>
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MS4A2, TOSO, LPXN, PTPRC, PTPN1, BTK, PLEXINA2, LCP1
|- 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=center" |
[[Cell cycle control]]<ref name="pmid20479288">{{cite journal |vauthors=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 |title=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 |journal=Blood |volume=116 |issue=9 |pages=1479–88 |date=September 2010 |pmid=20479288 |doi=10.1182/blood-2010-02-267476 |url=}}</ref><ref name="pmid15507668">{{cite journal |vauthors=Trøen G, Nygaard V, Jenssen TK, Ikonomou IM, Tierens A, Matutes E, Gruszka-Westwood A, Catovsky D, Myklebost O, Lauritzsen G, Hovig E, Delabie J |title=Constitutive expression of the AP-1 transcription factors c-jun, junD, junB, and c-fos and the marginal zone B-cell transcription factor Notch2 in splenic marginal zone lymphoma |journal=J Mol Diagn |volume=6 |issue=4 |pages=297–307 |date=November 2004 |pmid=15507668 |pmc=1867488 |doi=10.1016/S1525-1578(10)60525-9 |url=}}</ref><ref name="pmid24296945">{{cite journal |vauthors=Martínez N, Almaraz C, Vaqué JP, Varela I, Derdak S, Beltran S, Mollejo M, Campos-Martin Y, Agueda L, Rinaldi A, Kwee I, Gut M, Blanc J, Oscier D, Strefford JC, Martinez-Lopez J, Salar A, Sole F, Rodriguez-Peralto JL, Diez-Tascón C, García JF, Fraga M, Sebastián E, Alvés J, Menárguez J, González-Carreró J, Casado LF, Bayes M, Bertoni F, Gut I, Piris MA |title=Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation |journal=Leukemia |volume=28 |issue=6 |pages=1334–40 |date=June 2014 |pmid=24296945 |doi=10.1038/leu.2013.365 |url=}}</ref>
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CDKN2A, TP53, JUN, JUNB, JUND, FOS, EVI5
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=center" |
Lymphocyte development and regulation<ref name="pmid24349473">{{cite journal |vauthors=Parry M, Rose-Zerilli MJ, Gibson J, Ennis S, Walewska R, Forster J, Parker H, Davis Z, Gardiner A, Collins A, Oscier DG, Strefford JC |title=Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma |journal=PLoS ONE |volume=8 |issue=12 |pages=e83244 |date=2013 |pmid=24349473 |pmc=3862727 |doi=10.1371/journal.pone.0083244 |url=}}</ref><ref name="pmid25779943">{{cite journal |vauthors=Parry M, Rose-Zerilli MJ, Ljungström V, Gibson J, Wang J, Walewska R, Parker H, Parker A, Davis Z, Gardiner A, McIver-Brown N, Kalpadakis C, Xochelli A, Anagnostopoulos A, Fazi C, de Castro DG, Dearden C, Pratt G, Rosenquist R, Ashton-Key M, Forconi F, Collins A, Ghia P, Matutes E, Pangalis G, Stamatopoulos K, Oscier D, Strefford JC |title=Genetics and Prognostication in Splenic Marginal Zone Lymphoma: Revelations from Deep Sequencing |journal=Clin. Cancer Res. |volume=21 |issue=18 |pages=4174–4183 |date=September 2015 |pmid=25779943 |pmc=4490180 |doi=10.1158/1078-0432.CCR-14-2759 |url=}}</ref><ref name="pmid24296945">{{cite journal |vauthors=Martínez N, Almaraz C, Vaqué JP, Varela I, Derdak S, Beltran S, Mollejo M, Campos-Martin Y, Agueda L, Rinaldi A, Kwee I, Gut M, Blanc J, Oscier D, Strefford JC, Martinez-Lopez J, Salar A, Sole F, Rodriguez-Peralto JL, Diez-Tascón C, García JF, Fraga M, Sebastián E, Alvés J, Menárguez J, González-Carreró J, Casado LF, Bayes M, Bertoni F, Gut I, Piris MA |title=Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation |journal=Leukemia |volume=28 |issue=6 |pages=1334–40 |date=June 2014 |pmid=24296945 |doi=10.1038/leu.2013.365 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align=center |
NOTCH1, NOTCH2, SPEN, DTX1,SWAP70, MAML2,ARIDA3, NOTCH3, NOTCH4, PAX5, MAPK3K8
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=center" |
Chromosomal and transcriptional regulation<ref name="pmid25779943">{{cite journal |vauthors=Parry M, Rose-Zerilli MJ, Ljungström V, Gibson J, Wang J, Walewska R, Parker H, Parker A, Davis Z, Gardiner A, McIver-Brown N, Kalpadakis C, Xochelli A, Anagnostopoulos A, Fazi C, de Castro DG, Dearden C, Pratt G, Rosenquist R, Ashton-Key M, Forconi F, Collins A, Ghia P, Matutes E, Pangalis G, Stamatopoulos K, Oscier D, Strefford JC |title=Genetics and Prognostication in Splenic Marginal Zone Lymphoma: Revelations from Deep Sequencing |journal=Clin. Cancer Res. |volume=21 |issue=18 |pages=4174–4183 |date=September 2015 |pmid=25779943 |pmc=4490180 |doi=10.1158/1078-0432.CCR-14-2759 |url=}}</ref><ref name="pmid21113978">{{cite journal |vauthors=Rinaldi A, Forconi F, Arcaini L, Mian M, Sozzi E, Zibellini S, Baldini L, Franceschetti S, Gaidano G, Marasca R, Mollejo M, Piris MA, Tucci A, Facchetti F, Bhagat G, Favera RD, Rancoita PM, Zucca E, Kwee I, Bertoni F |title=Immunogenetics features and genomic lesions in splenic marginal zone lymphoma |journal=Br. J. Haematol. |volume=151 |issue=5 |pages=435–9 |date=December 2010 |pmid=21113978 |doi= |url=}}</ref>
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MLL2, MLL3, ARID1A, EP300, SYMD1, HIST1H1D, HIST1H1E, HIST1H2BI, SIN3A, GPS2, BCL6, POT1
|}
 
 
* Clonal rearrangements of the [[immunoglobulin]] genes (heavy and light chains) <ref name="dun1">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9635678&query_hl=24&itool=pubmed_ExternalLink]
* Clonal rearrangements of the [[immunoglobulin]] genes (heavy and light chains) <ref name="dun1">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9635678&query_hl=24&itool=pubmed_ExternalLink]
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</ref>  
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</ref>  
* Deletion 7q21-32 is seen in 40% of SMZL patients
* Most common genetic abnormality is the chromosomal deletion of 7q region.<ref name="pmid14681321">{{cite journal |vauthors=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 |title=Splenic marginal zone lymphomas presenting with splenomegaly and typical immunophenotype are characterized by allelic loss in 7q31-32 |journal=Mod. Pathol. |volume=16 |issue=12 |pages=1210–7 |date=December 2003 |pmid=14681321 |doi=10.1097/01.MP.0000095895.19756.77 |url=}}</ref>
*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.<ref name="pmid11337382">{{cite journal |vauthors=Hernández JM, García JL, Gutiérrez NC, Mollejo M, Martínez-Climent JA, Flores T, González MB, Piris MA, San Miguel JF |title=Novel genomic imbalances in B-cell splenic marginal zone lymphomas revealed by comparative genomic hybridization and cytogenetics |journal=Am. J. Pathol. |volume=158 |issue=5 |pages=1843–50 |date=May 2001 |pmid=11337382 |pmc=1891967 |doi=10.1016/S0002-9440(10)64140-5 |url=}}</ref><ref name="pmid15642391">{{cite journal |vauthors=Andersen CL, Gruszka-Westwood A, Atkinson S, Matutes E, Catovsky D, Pedersen RK, Pedersen BB, Pulczynski S, Hokland P, Jacobsen E, Koch J |title=Recurrent genomic imbalances in B-cell splenic marginal-zone lymphoma revealed by comparative genomic hybridization |journal=Cancer Genet. Cytogenet. |volume=156 |issue=2 |pages=122–8 |date=January 2005 |pmid=15642391 |doi=10.1016/j.cancergencyto.2004.04.026 |url=}}</ref><ref name="pmid20479288">{{cite journal |vauthors=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 |title=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 |journal=Blood |volume=116 |issue=9 |pages=1479–88 |date=September 2010 |pmid=20479288 |doi=10.1182/blood-2010-02-267476 |url=}}</ref>
* Translocations of the CDK6 gene  located at 7q21 have also been reported<ref name="cor1">
* Translocations of the CDK6 gene  located at 7q21 have also been reported<ref name="cor1">
[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10597225&query_hl=28&itool=pubmed_ExternalLink]
[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10597225&query_hl=28&itool=pubmed_ExternalLink]
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</ref>
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</ref>
===Immunophenotype===
===Immunophenotype===
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Revision as of 05:37, 28 December 2018

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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]

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

  • 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 Genes Involved

NFkB[1][2]

KLF2, TNFAIP3, MYD88, TRAF3, CARD11, MLL2, BTK, REL, SYK

Apoptosis[3][4]

BIRC3, TNFRSF5, TRAF3, TRAF5, BTK, XPB, APAF-1, IRF5, REL, PKCA,TMEM209

Cell communication[5][6][7]

MS4A2, TOSO, LPXN, PTPRC, PTPN1, BTK, PLEXINA2, LCP1

Cell cycle control[8][4][7]

CDKN2A, TP53, JUN, JUNB, JUND, FOS, EVI5

Lymphocyte development and regulation[5][2][7]

NOTCH1, NOTCH2, SPEN, DTX1,SWAP70, MAML2,ARIDA3, NOTCH3, NOTCH4, PAX5, MAPK3K8

Chromosomal and transcriptional regulation[2][9]

MLL2, MLL3, ARID1A, EP300, SYMD1, HIST1H1D, HIST1H1E, HIST1H2BI, SIN3A, GPS2, BCL6, POT1


  • Clonal rearrangements of the immunoglobulin genes (heavy and light chains) [10]
  • Most common genetic abnormality is the chromosomal deletion of 7q region.[11]
  • 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.[12][13][8]
  • Translocations of the CDK6 gene located at 7q21 have also been reported[14]

Immunophenotype
Antigen Splenic marginal zone lymphoma

CD20

Positive

CD79a

Positive

CD5

Negative

CD10

Negative

CD23

Negative

CD43

Negative

cyclin D1

Negative

Gross and Microscopic Pathology

  • Splenic marginal zone lymphoma (SMZL) is a subtype of non-hodgkin's lymphoma comprised of B-cells.[15]
  • It tends to involve spleen, bone marrow, liver and blood.[16]
  • 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.[17]
    • 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.
  • Bone Marrow:
    • Various patterns of Lymphocytic infiltration such as intrasinusoidal, nodular, interstitial and intravascular have been observed.[18]
    • Mixed pattern of lymphocytic infiltration with intrasinusoidal being predominant.[19][20]
    • 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.[21]
  • 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.[22]


  • Blood

References

  1. ↑ Clipson A, Wang M, de Leval L, Ashton-Key M, Wotherspoon A, Vassiliou G, Bolli N, Grove C, Moody S, Escudero-Ibarz L, Gundem G, Brugger K, Xue X, Mi E, Bench A, Scott M, Liu H, Follows G, Robles EF, Martinez-Climent JA, Oscier D, Watkins AJ, Du MQ (May 2015). "KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype". Leukemia. 29 (5): 1177–85. doi:10.1038/leu.2014.330. PMID 25428260.
  2. ↑ 2.0 2.1 2.2 Parry M, Rose-Zerilli MJ, Ljungström V, Gibson J, Wang J, Walewska R, Parker H, Parker A, Davis Z, Gardiner A, McIver-Brown N, Kalpadakis C, Xochelli A, Anagnostopoulos A, Fazi C, de Castro DG, Dearden C, Pratt G, Rosenquist R, Ashton-Key M, Forconi F, Collins A, Ghia P, Matutes E, Pangalis G, Stamatopoulos K, Oscier D, Strefford JC (September 2015). "Genetics and Prognostication in Splenic Marginal Zone Lymphoma: Revelations from Deep Sequencing". Clin. Cancer Res. 21 (18): 4174–4183. doi:10.1158/1078-0432.CCR-14-2759. PMC 4490180. PMID 25779943.
  3. ↑ Ruiz-Ballesteros E, Mollejo M, Rodriguez A, Camacho FI, Algara P, Martinez N, Pollán M, Sanchez-Aguilera A, Menarguez J, Campo E, Martinez P, Mateo M, Piris MA (September 2005). "Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis". Blood. 106 (5): 1831–8. doi:10.1182/blood-2004-10-3898. PMID 15914563.
  4. ↑ 4.0 4.1 Trøen G, Nygaard V, Jenssen TK, Ikonomou IM, Tierens A, Matutes E, Gruszka-Westwood A, Catovsky D, Myklebost O, Lauritzsen G, Hovig E, Delabie J (November 2004). "Constitutive expression of the AP-1 transcription factors c-jun, junD, junB, and c-fos and the marginal zone B-cell transcription factor Notch2 in splenic marginal zone lymphoma". J Mol Diagn. 6 (4): 297–307. doi:10.1016/S1525-1578(10)60525-9. PMC 1867488. PMID 15507668.
  5. ↑ 5.0 5.1 Parry M, Rose-Zerilli MJ, Gibson J, Ennis S, Walewska R, Forster J, Parker H, Davis Z, Gardiner A, Collins A, Oscier DG, Strefford JC (2013). "Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma". PLoS ONE. 8 (12): e83244. doi:10.1371/journal.pone.0083244. PMC 3862727. PMID 24349473.
  6. ↑ Fresquet V, Robles EF, Parker A, Martinez-Useros J, Mena M, Malumbres R, Agirre X, Catarino S, Arteta D, Osaba L, Mollejo M, Hernandez-Rivas JM, Calasanz MJ, Daibata M, Dyer MJ, Prosper F, Vizcarra E, Piris MÁ, Oscier D, Martinez-Climent JA (September 2012). "High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma". Br. J. Haematol. 158 (6): 712–26. doi:10.1111/j.1365-2141.2012.09226.x. PMID 22816737.
  7. ↑ 7.0 7.1 7.2 Martínez N, Almaraz C, Vaqué JP, Varela I, Derdak S, Beltran S, Mollejo M, Campos-Martin Y, Agueda L, Rinaldi A, Kwee I, Gut M, Blanc J, Oscier D, Strefford JC, Martinez-Lopez J, Salar A, Sole F, Rodriguez-Peralto JL, Diez-Tascón C, García JF, Fraga M, Sebastián E, Alvés J, Menárguez J, González-Carreró J, Casado LF, Bayes M, Bertoni F, Gut I, Piris MA (June 2014). "Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation". Leukemia. 28 (6): 1334–40. doi:10.1038/leu.2013.365. PMID 24296945.
  8. ↑ 8.0 8.1 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.
  9. ↑ Rinaldi A, Forconi F, Arcaini L, Mian M, Sozzi E, Zibellini S, Baldini L, Franceschetti S, Gaidano G, Marasca R, Mollejo M, Piris MA, Tucci A, Facchetti F, Bhagat G, Favera RD, Rancoita PM, Zucca E, Kwee I, Bertoni F (December 2010). "Immunogenetics features and genomic lesions in splenic marginal zone lymphoma". Br. J. Haematol. 151 (5): 435–9. PMID 21113978.
  10. ↑ [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
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ [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
  15. ↑ Zinzani PL (2012). "The many faces of marginal zone lymphoma". Hematology Am Soc Hematol Educ Program. 2012: 426–32. doi:10.1182/asheducation-2012.1.426. PMID 23233614.
  16. ↑ Arcaini L, Rossi D, Paulli M (April 2016). "Splenic marginal zone lymphoma: from genetics to management". Blood. 127 (17): 2072–81. doi:10.1182/blood-2015-11-624312. PMID 26989207.
  17. ↑ Papadaki T, Stamatopoulos K, Belessi C, Pouliou E, Parasi A, Douka V, Laoutaris N, Fassas A, Anagnostopoulos A, Anagnostou D (March 2007). "Splenic marginal-zone lymphoma: one or more entities? A histologic, immunohistochemical, and molecular study of 42 cases". Am. J. Surg. Pathol. 31 (3): 438–46. doi:10.1097/01.pas.0000213419.08009.b0. PMID 17325486.
  18. ↑ Mohanpuria A, Kumar V, Suteri P, Marwah S, Nigam AS (July 2017). "Important Diagnostic Clues for Diagnosing Splenic Marginal Zone Lymphoma in Absence of Splenic Histology". J Clin Diagn Res. 11 (7): ED15–ED17. doi:10.7860/JCDR/2017/27149.10190. PMC 5583942. PMID 28892912.
  19. ↑ Iannitto E, Ambrosetti A, Ammatuna E, Colosio M, Florena AM, Tripodo C, Minardi V, Calvaruso G, Mitra ME, Pizzolo G, Menestrina F, Franco V (November 2004). "Splenic marginal zone lymphoma with or without villous lymphocytes. Hematologic findings and outcomes in a series of 57 patients". Cancer. 101 (9): 2050–7. doi:10.1002/cncr.20596. PMID 15389479.
  20. ↑ Kent SA, Variakojis D, Peterson LC (May 2002). "Comparative study of marginal zone lymphoma involving bone marrow". Am. J. Clin. Pathol. 117 (5): 698–708. doi:10.1309/MECJ-GLK1-WEBW-UEVE. PMID 12090417.
  21. ↑ Ponzoni M, Kanellis G, Pouliou E, Baliakas P, Scarfò L, Ferreri AJ, Doglioni C, Bikos V, Dagklis A, Anagnostopoulos A, Ghia P, Stamatopoulos K, Papadaki T (November 2012). "Bone marrow histopathology in the diagnostic evaluation of splenic marginal-zone and splenic diffuse red pulp small B-cell lymphoma: a reliable substitute for spleen histopathology?". Am. J. Surg. Pathol. 36 (11): 1609–18. doi:10.1097/PAS.0b013e318271243d. PMID 23073320.
  22. ↑ Mollejo M, Lloret E, Menárguez J, Piris MA, Isaacson PG (July 1997). "Lymph node involvement by splenic marginal zone lymphoma: morphological and immunohistochemical features". Am. J. Surg. Pathol. 21 (7): 772–80. PMID 9236833.

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