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Classification of B-cell non-Hodgkin lymphomas (NHL)

Written2000-02Antonio Cuneo
Hematology Section, Dept. Of Biomedical Sciences, University of Ferrara, 44100 Ferrara Italy

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
Atlas_Id 2067
Note B-cell NHL include a number of clinicopathologic subsets of lymphoid neoplasms having heterogeneous features. This situation is reflected by variations in the classification systems that were proposed over the last decade. Cytogenetic findings were recognized to help defining a rationale biologic ground for the nosologic classification of lymphomas.
An outlook of the salient cytogenetic entities in this spectrum of disorders is presented herein; a complete illustration of the cytogenetic profile of each disease is provided in specific cards. Unless otherwise specified the WHO classification system will be used.
Legend for immunophenotypes (below): +: positive in >90% of the cases; +/-: positive in more than 50% of the cases; -/+: positive in less than 50% of cases; -: positive in <10% of the cases; pan-B markers include CD19; CD20; CD79a; R = rearranged; sIg: surface immunoglobulins; cyIg: cytoplasmic Ig; IgV genes: genes encoding for the variable portion of the Ig.

Clinics and Pathology

Disease Small lymphocytic lymphoma (SLL)
Phenotype / cell stem origin
  • Histologic subset and Immunophenotype: Pan-B+; CD5+; CD23+; CD10-; sIgM+ faint.
  • Putative cell of origin: CD5+ virgin B-cell with germline IgV genes ( as was recently demonstrated to be the case with chronic lymphocytic leukemia, the leukemic counterpart of SLL, it is likely that part of the cases may derive from post-germinal centre quiescent B-cells that harbour hypermutated IgV genes)
  • Clinics
  • Indolent disease;
  • leukemic involvement by lymphoid cells, including prolymphocytes and/or paraimmunoblasts Splenomegaly
  • Cytogenetics del(6)(q21-23) (20-30% of the cases)

    Disease Lymphoplasmacytic lymphoma
    Phenotype / cell stem origin
  • Histologic subset and Immunophenotype: Pan-B+; CD5-; CD10-; cyIgM+
  • Putative cell of origin: Peripheral B-lymphocyte transforming into plasma cell with mutated IgV genes and ongoing mutations
  • Clinics Indolent low-grade disease, with possible clinical and/or histologic progression
    Cytogenetics
  • t(9;14)(p13;q32) PAX5/IgH (50% of cases)

  • Disease Follicle centre cell lymphoma
    Phenotype / cell stem origin
  • Histologic subset and Immunophenotype: Pan-B+; CD10+/-; CD5-; sIg+
  • Putative cell of origin: Centrocytes / centroblasts of germinal centre origin with somatic hypermutation of the IgV genes and ongoing mutations (antigen driven stimulation)
  • Clinics
  • Indolent. Advanced stages predominate.
  • Conflicting data as to the prognostic significance of the t(14;18)/BCL2
  • Cytogenetics
  • t(14;18)(q32;q21) / BCL2 Rearr (70-80% of cases)

  • Disease Diffuse large cell lymphoma
    Phenotype / cell stem origin
  • Histologic subset and Immunophenotype: CD19+; CD22+; CD10-/+; SIg+
  • Putative cell of origin: Large transformed B-cells harbouring somatic hypermutation of the Ig genes (ongoing mutations in some cases)
  • Clinics
  • Usually aggressive
  • Immunoblastic lymphoma (Kiel classification) do worse than centroblastic lymphomas
  • No convincing demonstration that any "primary" cytogenetic / molecular defect has prognostic significance; complex karyotype confers a shorter survival
  • Cytogenetics
  • t(14;18) and p53 mutations (20% of the cases)
  • t(3;V)(q27;V)/ BCL6 Rearr (6-30% of cases (% variations depending on detection methods: molecular genetics and FISH more sensitive that conventional cytogenetics))
  • or variants c-MYC Rearr (7-10% of cases)

  • Disease Burkitt's lymphoma
    Phenotype / cell stem origin
  • Histologic subset and Immunophenotype: Pan-B+; TdT-; CD10+; CD5-; sIgM+
  • Putative cell of origin: Peripheral B-cells that have encountered the antigen and harbours somatic hypermutation of the Ig genes
  • Clinics
  • Extremely aggressive disease
  • Specific treatment mandatory
  • Cytogenetics
  • t(8;14)(q24;q32) or variants / c-MYC R earr (80% of the cases)

  • Disease Burkitt-like lymphoma
    Phenotype / cell stem origin
  • Histologic subset and Immunophenotype: Pan-B+; TdT-; CD10-/+ CD5-; sIg+
  • Putative cell of origin: Peripheral B-cells that have encountered the antigen
  • Clinics
  • Aggressive disease
  • Cases with dual 8;14 and 14;18 translocations have a worse outcome (data requiring confirmation -1 study only)
  • Cytogenetics
  • t(8;14) or variants (25% of cases)
  • t(8;14)+ t(14;18) (30% of cases)

  • Disease Mantle cell lymphoma
    Phenotype / cell stem origin
  • Histologic subset and Immunophenotype: Pan-B +; CD5+; CD23-; CD10-/+; sIgM+ bright
  • Putative cell of origin: CD5+ B-cells of the follicle mantle having germline IgV gene sequences
  • Clinics
  • Advanced stages predominate
  • Response to chemotherapy often unsatisfactory
  • Short survival
  • Complex karyotype carries an unfavourable prognostic significance
  • Cytogenetics
  • t(11;14)(q13;q32) / BCL1 Rearr (50-90%) (molecular genetic methods have limited application due to variability of breakpoints; FISH is the most sensitive technique)

  • Disease Marginal zone B-cell lymphoma (MZBCL)
    Phenotype / cell stem origin
  • Histologic subset and Immunophenotype: pan-B+; CD5-/+; CD10-; CD23-; CD11c+/-; cyIg + (40% of the cells), sIgM+ bright; sIgD-)
  • Putative cell of origin: Marginal zone lymphocytes harbouring hypermutated IgV genes
  • Cytogenetics
  • t(11;18)(q21;q21) / PI2 / MLT fusion (30-50% of the low-grade MALT): Extra-nodal low-grade MALT lymphoma; indolent disease
  • t(1;14)(p21;q32): Extra-nodal MALT lymphoma
  • del(7)(q22-31) (40% of the cases): Splenic MZBCL
  • /+3q (30-70% of the cases): Nodal, extra-nodal and splenic MZBCL
  • Bibliography

    Cytogenetic profile of lymphoma of follicle mantle lineage: correlation with clinicobiologic features.
    Cuneo A, Bigoni R, Rigolin GM, Roberti MG, Bardi A, Piva N, Milani R, Bullrich F, Veronese ML, Croce C, Birg F, Döhner H, Hagemeijer A, Castoldi G
    Blood. 1999 ; 93 (4) : 1372-1380.
    PMID 9949181
     
    The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas.
    Dierlamm J, Baens M, Wlodarska I, Stefanova-Ouzounova M, Hernandez JM, Hossfeld DK, De Wolf-Peeters C, Hagemeijer A, Van den Berghe H, Marynen P
    Blood. 1999 ; 93 (11) : 3601-3609.
    PMID 10339464
     
    Cellular origin of human B-cell lymphomas.
    Küppers R, Klein U, Hansmann ML, Rajewsky K
    The New England journal of medicine. 1999 ; 341 (20) : 1520-1529.
    PMID 10559454
     
    Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma.
    Kramer MH, Hermans J, Wijburg E, Philippo K, Geelen E, van Krieken JH, de Jong D, Maartense E, Schuuring E, Kluin PM
    Blood. 1998 ; 92 (9) : 3152-3162.
    PMID 9787151
     
    Correlation of bcl-2 rearrangement with clinical characteristics and outcome in indolent follicular lymphoma.
    López-Guillermo A, Cabanillas F, McDonnell TI, McLaughlin P, Smith T, Pugh W, Hagemeister F, Rodríguez MA, Romaguera JE, Younes A, Sarris AH, Preti HA, Lee MS
    Blood. 1999 ; 93 (9) : 3081-3087.
    PMID 10216105
     
    Small noncleaved, non-Burkitt's (Burkit-Like) lymphoma: cytogenetics predict outcome and reflect clinical presentation.
    Macpherson N, Lesack D, Klasa R, Horsman D, Connors JM, Barnett M, Gascoyne RD
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (5) : 1558-1567.
    PMID 10334544
     
    t(9;14)(p13;q32) denotes a subset of low-grade non-Hodgkin's lymphoma with plasmacytoid differentiation.
    Offit K, Parsa NZ, Filippa D, Jhanwar SC, Chaganti RS
    Blood. 1992 ; 80 (10) : 2594-2599.
    PMID 1384792
     
    Genetics of small lymphocyte disorders.
    Panayiotidis P, Kotsi P
    Seminars in hematology. 1999 ; 36 (2) : 171-177.
    PMID 10319386
     
    Research of complementary/alternative medicine therapies in oncology: promising but challenging.
    Richardson MA
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (11 Suppl) : 38-43.
    PMID 10630261
     
    Prognostic value of chromosomal abnormalities in follicular lymphoma.
    Tilly H, Rossi A, Stamatoullas A, Lenormand B, Bigorgne C, Kunlin A, Monconduit M, Bastard C
    Blood. 1994 ; 84 (4) : 1043-1049.
    PMID 8049424
     
    Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types.
    Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer MJ
    Cell. 1999 ; 96 (1) : 35-45.
    PMID 9989495
     

    Citation

    This paper should be referenced as such :
    Cuneo, A
    Classification of B-cell non-Hodgkin's lymphomas (NHL)
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(1):24-26.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Anomalies/BNHLClassifID2067.html


    Other genes implicated (Data extracted from papers in the Atlas) [ 53 ]

    Genes AKT1 ANG BACH2 BCL2L11 BCL6 BCL7B BCLAF1 BIRC2 BIRC3 BUB1
    CALR CD44 CD74 CDC25A CDC25A CHEK2 COL1A2 CSE1L CTCF DCC
    DIABLO EIF4E FAS FAU FCER2 FCGR2B FGF2 FLI1 FOXP1 FSTL3
    H2AFX HYAL2 ID4 IL21R IL22RA1 MAGEA3 MALT1 MDM2 MIXL1 MMP26
    NME1 PASD1 PLK1 PPM1D PTPN7 RBBP8 RNASET2 RPA2 SET TNFAIP3
    TP53BP2 TXN ZAP70

    External links

    arrayMap (UZH-SIB Zurich)
    COSMICHisto = - Site = haematopoietic_and_lymphoid_tissue (COSMIC)
    arrayMap[select an item]
     
     
    Other databaseLymphoma Overview - Disease Synopsis [canSAR]
    Disease databaseClassification of B-cell non-Hodgkin lymphomas (NHL)
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed


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