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Tumor Biology
Published in: Tumor Biology 3/2016

01-03-2016 | Original Article

CD20-negative diffuse large B cell lymphoma: a comprehensive analysis of 695 cases

Authors: Jing Li, Shu Zhao, Jingxuan Wang, Jingyu Chen, Wen Wen, Qingyuan Zhang

Published in: Tumor Biology | Issue 3/2016

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Abstract

CD20 expression is absent in a variety of diffuse large B cell lymphomas (DLBCLs), including plasmablastic lymphoma, primary effusion lymphoma, anaplastic lymphoma, kinase-positive DLBCL, and large B cell lymphoma arising in human herpesvirus 8-associated multicentric Castleman disease. These rare and heterogeneous tumors are characterized by the presence of proliferating immunoblasts with similar transcriptional profiles as those of plasma cells and are typically associated with highly aggressive pathologies, with high levels of chemotherapy resistance and low survival rates; thus, they pose significant diagnostic and treatment challenges. We conducted a systematic literature review of the limited existing clinical data to summarize the current knowledge regarding the biological basis, diagnostic limits, and potential therapeutic targets of distinct variants of CD20-negative DLBCL. This review will hopefully increase the awareness of these rare disorders among clinicians and pathologists and prompt basic and clinical research.
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Literature
1.
Klein U, Dalla-Favera R. Unexpected steps in plasma-cell differentiation. Immunity. 2007;26:543–4.CrossRefPubMed
2.
Klein U, Dalla-Favera R. Germinal centres: role in b-cell physiology and malignancy. Nat Rev Immunol. 2008;8:22–33.CrossRefPubMed
3.
Shaffer AL, Lin KI, Kuo TC, Yu X, Hurt EM, Rosenwald A, et al. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature b cell gene expression program. Immunity. 2002;17:51–62.CrossRefPubMed
4.
Montes-Moreno S, Gonzalez-Medina AR, Rodriguez-Pinilla SM, Maestre L, Sanchez-Verde L, Roncador G, et al. Aggressive large b-cell lymphoma with plasma cell differentiation: Immunohistochemical characterization of plasmablastic lymphoma and diffuse large b-cell lymphoma with partial plasmablastic phenotype. Haematologica. 2010;95:1342–9.CrossRefPubMedPubMedCentral
5.
Swerdllow S, Campo E, Harris NL. Who classification of tumours of haematopoietic and lymphoid tissues. France: IARC Press; 2008. 2008.
6.
Delecluse HJ, Anagnostopoulos I, Dallenbach F, Hummel M, Marafioti T, Schneider U, et al. Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. Blood. 1997;89:1413–20.PubMed
7.
Borenstein J, Pezzella F, Gatter KC. Plasmablastic lymphomas may occur as post-transplant lymphoproliferative disorders. Histopathology. 2007;51:774–7.CrossRefPubMed
8.
Campo E, Chott A, Kinney MC, Leoncini L, Meijer CJ, Papadimitriou CS, et al. Update on extranodal lymphomas, conclusions of the workshop held by the eahp and the sh in Thessaloniki, Greece. Histopathology. 2006;48:481–504.CrossRefPubMedPubMedCentral
9.
Cannuyer J, Loriot A, Parvizi GK, De Smet C. Epigenetic hierarchy within the magea1 cancer-germline gene: promoter DNA methylation dictates local histone modifications. PLoS One. 2013;8:e58743.CrossRefPubMedPubMedCentral
10.
Choi J, Chang H. The expression of mage and ssx, and correlation of cox2, vegf, and survivin in colorectal cancer. Anticancer Res. 2012;32:559–64.PubMed
11.
Eichmuller S, Usener D, Thiel D, Schadendorf D. Tumor-specific antigens in cutaneous t-cell lymphoma: expression and sero-reactivity. Int J Cancer. 2003;104:482–7.CrossRefPubMed
12.
Bohlius J, Schmidlin K, Costagliola D, Fatkenheuer G, May M, Caro Murillo AM, et al. Prognosis of hiv-associated non-Hodgkin lymphoma in patients starting combination antiretroviral therapy. AIDS. 2009;23:2029–37.CrossRefPubMed
13.
Castillo JJ, Winer ES, Stachurski D, Perez K, Jabbour M, Milani C, et al. Clinical and pathological differences between human immunodeficiency virus-positive and human immunodeficiency virus-negative patients with plasmablastic lymphoma. Leuk Lymphoma. 2010;51:2047–53.CrossRefPubMed
14.
Morscio J, Dierickx D, Nijs J, Verhoef G, Bittoun E, Vanoeteren X, et al. Clinicopathologic comparison of plasmablastic lymphoma in hiv-positive, immunocompetent, and posttransplant patients: single-center series of 25 cases and meta-analysis of 277 reported cases. Am J Surg Pathol. 2014;38:875–86.CrossRefPubMed
15.
Adam P, Bonzheim I, Fend F, Quintanilla-Martinez L. Epstein-Barr virus-positive diffuse large b-cell lymphomas of the elderly. Adv Anat Pathol. 2011;18:349–55.CrossRefPubMed
16.
Knecht H, Berger C, Rothenberger S, Odermatt BF, Brousset P. The role of Epstein-Barr virus in neoplastic transformation. Oncology. 2001;60:289–302.CrossRefPubMed
17.
Bibas M, Antinori A. Ebv and hiv-related lymphoma. Mediterranean J Hematol Infect Dis. 2009;1:e2009032.
18.
Aboulafia DM, Ratner L, Miles SA, Harrington Jr WJ. Antiviral and immunomodulatory treatment for aids-related primary central nervous system lymphoma: aids malignancies consortium pilot study 019. Clin Lymphoma Myeloma. 2006;6:399–402.CrossRefPubMed
19.
Castillo JJ, Furman M, Beltran BE, Bibas M, Bower M, Chen W, et al. Human immunodeficiency virus-associated plasmablastic lymphoma: poor prognosis in the era of highly active antiretroviral therapy. Cancer. 2012;118:5270–7.CrossRefPubMed
20.
Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463:899–905.CrossRefPubMedPubMedCentral
21.
Valera A, Balague O, Colomo L, Martinez A, Delabie J, Taddesse-Heath L, et al. Ig/myc rearrangements are the main cytogenetic alteration in plasmablastic lymphomas. Am J Surg Pathol. 2010;34:1686–94.PubMedPubMedCentral
22.
23.
Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. Bet bromodomain inhibition as a therapeutic strategy to target c-myc. Cell. 2011;146:904–17.CrossRefPubMedPubMedCentral
24.
Hermiston ML, Xu Z, Weiss A. Cd45: a critical regulator of signaling thresholds in immune cells. Annu Rev Immunol. 2003;21:107–37.CrossRefPubMed
25.
Justement LB. The role of the protein tyrosine phosphatase cd45 in regulation of b lymphocyte activation. Int Rev Immunol. 2001;20:713–38.CrossRefPubMed
26.
Oliveira DM, Goodell MA. Transient rna interference in hematopoietic progenitors with functional consequences. Genesis. 2003;36:203–8.CrossRefPubMed
27.
Baker M, Gamble J, Tooze R, Higgins D, Yang FT, O'Brien PC, et al. Development of t-leukaemias in cd45 tyrosine phosphatase-deficient mutant lck mice. EMBO J. 2000;19:4644–54.CrossRefPubMedPubMedCentral
28.
Carbone A, Vaccher E, Gloghini A, Pantanowitz L, Abayomi A, de Paoli P, et al. Diagnosis and management of lymphomas and other cancers in hiv-infected patients. Nat Rev Clin Oncol. 2014;11:223–38.CrossRefPubMed
29.
Shapiro-Shelef M, Lin K-I, McHeyzer-Williams LJ, Liao J, McHeyzer-Williams MG, Calame K. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory b cells. Immunity. 2003;19:607–20.CrossRefPubMed
30.
Shi Y, Hou Y, Hu Q, Su J, Zeng H, Tan Y. A rare case of hhv-8-positive/hiv-negative/ebv-negative primary effusion lymphoma in a renal transplant recipient. Cytopathology. 2012;23:137–9.CrossRefPubMed
31.
Jaffe ES. The 2008 who classification of lymphomas: implications for clinical practice and translational research. Hematol Am Soc Hematol Educ Prog. 2009;2009:523–31.
32.
Trivedi P, Takazawa K, Zompetta C, Cuomo L, Anastasiadou E, Carbone A, et al. Infection of hhv-8+ primary effusion lymphoma cells with a recombinant Epstein-Barr virus leads to restricted ebv latency, altered phenotype, and increased tumorigenicity without affecting tcl1 expression. Blood. 2004;103:313–6.CrossRefPubMed
33.
Castillo JJ, Shum H, Lahijani M, Winer ES, Butera JN. Prognosis in primary effusion lymphoma is associated with the number of body cavities involved. Leuk Lymphoma. 2012;53:2378–82.CrossRefPubMed
34.
Bhatt S, Ashlock B, Natkunam Y, Ramos JC, Mesri E, Lossos IS: Preclinical activity of brentuximab vedotin (sgn-35) in primary effusion lymphoma (pel) clinically relevant abstract, 2011
35.
36.
Boulanger E, Agbalika F, Maarek O, Daniel MT, Grollet L, Molina JM, et al. A clinical, molecular and cytogenetic study of 12 cases of human herpesvirus 8 associated primary effusion lymphoma in hiv-infected patients. Hematol J. 2001;2:172–9.CrossRefPubMed
37.
Komanduri KV, Luce JA, McGrath MS, Herndier BG, Ng VL. The natural history and molecular heterogeneity of hiv-associated primary malignant lymphomatous effusions. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;13:215–26.CrossRefPubMed
38.
Soulier J, Grollet L, Oksenhendler E, Miclea JM, Cacoub P, Baruchel A, et al. Molecular analysis of clonality in castleman’s disease. Blood. 1995;86:1131–8.PubMed
39.
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579–86.CrossRefPubMed
40.
Siddiqi T, Joyce RM. A case of hiv-negative primary effusion lymphoma treated with bortezomib, pegylated liposomal doxorubicin, and rituximab. Clin Lymphoma Myeloma. 2008;8:300–4.CrossRefPubMed
41.
Spina M, Gaidano G, Carbone A, Capello D, Tirelli U. Highly active antiretroviral therapy in human herpesvirus-8-related body-cavity-based lymphoma. AIDS. 1998;12:955–6.PubMed
42.
Aoki Y, Tosato G. Hiv-1 tat enhances Kaposi sarcoma-associated herpesvirus (kshv) infectivity. Blood. 2004;104:810–4.CrossRefPubMed
43.
Delsol G, Lamant L, Mariame B, Pulford K, Dastugue N, Brousset P, et al. A new subtype of large b-cell lymphoma expressing the alk kinase and lacking the 2; 5 translocation. Blood. 1997;89:1483–90.PubMed
44.
Laurent C, Do C, Gascoyne RD, Lamant L, Ysebaert L, Laurent G, et al. Anaplastic lymphoma kinase-positive diffuse large b-cell lymphoma: a rare clinicopathologic entity with poor prognosis. J Clin Oncol. 2009;27:4211–6.CrossRefPubMed
45.
Lee SE, Kang SY, Takeuchi K, Ko YH. Identification of ranbp2-alk fusion in alk positive diffuse large b-cell lymphoma. Hematol Oncol. 2014;32:221–4.CrossRefPubMed
46.
Takeuchi K, Soda M, Togashi Y, Ota Y, Sekiguchi Y, Hatano S, et al. Identification of a novel fusion, sqstm1-alk, in alk-positive large b-cell lymphoma. Haematologica. 2011;96:464–7.CrossRefPubMed
47.
Van Roosbroeck K, Cools J, Dierickx D, Thomas J, Vandenberghe P, Stul M, et al. Alk-positive large b-cell lymphomas with cryptic sec31a-alk and npm1-alk fusions. Haematologica. 2010;95:509–13.CrossRefPubMedPubMedCentral
48.
De Paepe P, Baens M, van Krieken H, Verhasselt B, Stul M, Simons A, et al. Alk activation by the cltc-alk fusion is a recurrent event in large b-cell lymphoma. Blood. 2003;102:2638–41.CrossRefPubMed
49.
Adam P, Katzenberger T, Seeberger H, Gattenlohner S, Wolf J, Steinlein C, et al. A case of a diffuse large b-cell lymphoma of plasmablastic type associated with the t(2;5)(p23;q35) chromosome translocation. Am J Surg Pathol. 2003;27:1473–6.CrossRefPubMed
50.
Onciu M, Behm FG, Downing JR, Shurtleff SA, Raimondi SC, Ma Z, et al. Alk-positive plasmablastic b-cell lymphoma with expression of the npm-alk fusion transcript: report of 2 cases. Blood. 2003;102:2642–4.CrossRefPubMed
51.
d'Amore ES, Visco C, Menin A, Famengo B, Bonvini P, Lazzari E. Stat3 pathway is activated in alk-positive large b-cell lymphoma carrying sqstm1-alk rearrangement and provides a possible therapeutic target. Am J Surg Pathol. 2013;37:780–6.CrossRefPubMed
52.
Nieborowska-Skorska M, Slupianek A, Xue L, Zhang Q, Raghunath PN, Hoser G, et al. Role of signal transducer and activator of transcription 5 in nucleophosmin/ anaplastic lymphoma kinase-mediated malignant transformation of lymphoid cells. Cancer Res. 2001;61:6517–23.PubMed
53.
Zamo A, Chiarle R, Piva R, Howes J, Fan Y, Chilosi M, et al. Anaplastic lymphoma kinase (alk) activates stat3 and protects hematopoietic cells from cell death. Oncogene. 2002;21:1038–47.CrossRefPubMed
54.
Zhang Q, Wang HY, Liu X, Wasik MA. Stat5a is epigenetically silenced by the tyrosine kinase npm1-alk and acts as a tumor suppressor by reciprocally inhibiting npm1-alk expression. Nat Med. 2007;13:1341–8.CrossRefPubMed
55.
Bai RY, Ouyang T, Miething C, Morris SW, Peschel C, Duyster J. Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/akt antiapoptotic signaling pathway. Blood. 2000;96:4319–27.PubMed
56.
Li J, Ouyang J, Zhou R, Chen B, Xu Y. Promising response of anaplastic lymphoma kinase-positive large b-cell lymphoma to crizotinib salvage treatment: case report and review of literature. Int J Clin Exp Med. 2015;8:6977–85.PubMedPubMedCentral
57.
Wass M, Behlendorf T, Schadlich B, Mottok A, Rosenwald A, Schmoll HJ, et al. Crizotinib in refractory alk-positive diffuse large b-cell lymphoma: a case report with a short-term response. Eur J Haematol. 2014;92:268–70.CrossRefPubMed
58.
Horibe K, Braiteh F, Huang H-q, Shi Y, Taylor MH, Brega N, et al. Safety and clinical activity of crizotinib in patients with alk-rearranged hematologic malignancies. Blood. 2013;122:4342.
59.
Cerchietti L, Damm-Welk C, Vater I, Klapper W, Harder L, Pott C, et al. Inhibition of anaplastic lymphoma kinase (alk) activity provides a therapeutic approach for cltc-alk-positive human diffuse large b cell lymphomas. PLoS One. 2011;6:e18436.CrossRefPubMedPubMedCentral
60.
Oksenhendler E, Boulanger E, Galicier L, Du MQ, Dupin N, Diss TC, et al. High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with hiv infection and multicentric castleman disease. Blood. 2002;99:2331–6.CrossRefPubMed
61.
Jaffe ES. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. France: Iarc; 2001.
62.
Du MQ, Liu H, Diss TC, Ye H, Hamoudi RA, Dupin N, et al. Kaposi sarcoma-associated herpesvirus infects monotypic (igm lambda) but polyclonal naive b cells in castleman disease and associated lymphoproliferative disorders. Blood. 2001;97:2130–6.CrossRefPubMed
63.
Oksenhendler E, Carcelain G, Aoki Y, Boulanger E, Maillard A, Clauvel JP, et al. High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and c reactive protein correlate with exacerbation of multicentric castleman disease in hiv-infected patients. Blood. 2000;96:2069–73.PubMed
64.
Keller SA, Hernandez-Hopkins D, Vider J, Ponomarev V, Hyjek E, Schattner EJ, et al. Nf-kappab is essential for the progression of kshv- and ebv-infected lymphomas in vivo. Blood. 2006;107:3295–302.CrossRefPubMedPubMedCentral
65.
Mylona EE, Baraboutis IG, Lekakis LJ, Georgiou O, Papastamopoulos V, Skoutelis A. Multicentric castleman’s disease in hiv infection: a systematic review of the literature. AIDS Rev. 2008;10:25–35.PubMed
66.
Zeng Y, Zhang X, Huang Z, Cheng L, Yao S, Qin D, et al. Intracellular tat of human immunodeficiency virus type 1 activates lytic cycle replication of Kaposi's sarcoma-associated herpesvirus: role of jak/stat signaling. J Virol. 2007;81:2401–17.CrossRefPubMed
67.
Bhutani M, Polizzotto MN, Uldrick TS, Yarchoan R. Kaposi sarcoma-associated herpesvirus-associated malignancies: epidemiology, pathogenesis, and advances in treatment. Semin Oncol. 2015;42:223–46.CrossRefPubMed
68.
Gerard L, Michot JM, Burcheri S, Fieschi C, Longuet P, Delcey V, et al. Rituximab decreases the risk of lymphoma in patients with hiv-associated multicentric castleman disease. Blood. 2012;119:2228–33.CrossRefPubMed
69.
Uldrick TS, Polizzotto MN, Aleman K, Wyvill KM, Marshall V, Whitby D, et al. Rituximab plus liposomal doxorubicin in hiv-infected patients with kshv-associated multicentric castleman disease. Blood. 2014;124:3544–52.CrossRefPubMedPubMedCentral
70.
Sarosiek KA, Cavallin LE, Bhatt S, Toomey NL, Natkunam Y, Blasini W, et al. Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma. Proc Natl Acad Sci U S A. 2010;107:13069–74.CrossRefPubMedPubMedCentral
Metadata
Title
CD20-negative diffuse large B cell lymphoma: a comprehensive analysis of 695 cases
Authors
Jing Li
Shu Zhao
Jingxuan Wang
Jingyu Chen
Wen Wen
Qingyuan Zhang
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4205-5

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