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Classification of B-cell non-Hodgkin's lymphomas (NHL) : cytogenetic entities, immunopheneotype and clinical features

Antonio Cuneo

 

Dipartimento di Scienze Biomediche - Sezione di Ematologia
Università di Ferrara - Via Savonarola, 9 - 44100 FERRARA - ITALY
tel. int+39.0532.236978; fax: int+39.0532.212142; e-mail sse@dns.unife.it

February 2000

 

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.

In this table an outlook of the salient cytogenetic entities in this spectrum of disorders is presented; 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.

 

Histologic subset and Immunophenotype

Putative cell of origin

Cytogenetic entitiy and corresponding clinical features

Small lymphocytic lymphoma (SLL)

Pan-B+; CD5+; CD23+; CD10-; sIgM+ faint

CD5+ virgin B-cell with germline IgV genes1

del(6)(q21-23) (20-30% of the cases)

  • Indolent disease; leukemic involvement by lymphoid cells, including prolymphocytes and/or paraimmunoblasts
  • Splenomegaly
  • Lymphoplasmacytic lymphoma

    Pan-B+; CD5-; CD10-; cyIgM+

    Peripheral B-lymphocyte transforming into plasma cell with mutated IgV genes and ongoing mutations

    t(9;14)(p13;q32) PAX5/IgH (50% of cases)

  • Indolent low-grade disease, with possible clinical and/or histologic progression
  • Follicle centre cell lymphoma

    Pan-B+; CD10+/-; CD5-; sIg+

    Centrocytes / centroblasts of germinal centre origin with somatic hypermutation of the IgV genes and ongoing mutations (antigen driven stimulation)

    t(14;18)(q32;q21) / BCL2 Rearr (70-80% of cases)

  • Indolent. Advanced stages predominate.
  • Conflicting data as to the prognostic significance of the t(14;18)/BCL2Rearr
  • Diffuse large cell lymphoma

    CD19+; CD22+;

    CD10-/+; SIg+

    Large transformed B-cells harbouring somatic hypermutation of the Ig genes

    (ongoing mutations in some cases)

  • t(14;18) and p53 mutations (20% of the cases)
  • t(3;V)(q27;V)/ BCL6 Rearr (6-30% of cases2)
  • t(8;14)(q24;q32) or variants c-MYC Rearr (7-10% of cases)
  • 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
  • Burkitt's lymphoma

    Pan-B+; TdT-; CD10+; CD5-; sIgM+

    Peripheral B-cells that have encountered the antigen and harbours somatic hypermutation of the Ig genes

    t(8;14)(q24;q32) or variants /

  • Extremely aggressive disease
  • Specific treatment mandatory
  • Burkitt-like lymphoma Pan-B+; TdT-; CD10-/+ CD5-; sIg+

    Peripheral B-cells that have encountered the antigen

  • t(8;14) or variants (25% of cases)
  • t(8;14)+ t(14;18) (30% of cases)
  • Aggressive disease
  • Cases with dual 8;14 and 14;18 translocations have a worse outcome3
  • Mantle cell lymphoma

    Pan-B +; CD5+;

    CD23-; CD10-/+; sIgM+ bright

    CD5+ B-cells of the follicle mantle having germline IgV gene sequences

    t(11;14)(q13;q32) / BCL1 Rearr (50-90%4)

  • Advanced stages predominate
  • Response to chemotherapy often unsatisfactory
  • Short survival
  • Complex karyotype carries an unfavourable prognostic significance
  • Marginal zone B-cell lymphoma (MZBCL)

    pan-B+; CD5-/+; CD10-; CD23-; CD11c+/-; cyIg + (40% of the cells), sIgM+ bright; sIgD-)

    Marginal zone lymphocytes harbouring hypermutated IgV genes

    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

    +3/+3q

    (30-70% of the cases)

    Nodal, extra-nodal and splenic MZBCL

    Legend : +: 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.

    Comments

    1. 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;
    2. % variations depending on detection methods: molecular genetics and FISH more sensitive that conventional cytogenetics;
    3. data requiring confirmation (1 study only, see Macpherson et al., 1999);
    4. molecular genetic methods have limited application due to variability of breakpoints; FISH is the most sensitive technique.

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    t(9;14)(p13;q32) denotes a subset of low-grade non-Hodgkin's lymphoma with plasmacytoid differentiation.
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    Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types.
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    Written2000-02Antonio Cuneo
    Section, Dept. Of Biomedical Sciences, University of Ferrara, 44100 Ferrara Italy
    Updated2001-05David Gisselsson
    of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

    Citation

    This paper should be referenced as such :
    Gisselsson D
    Classification of B-cell non-Hodgkin's lymphomas (NHL) : cytogenetic entities, immunopheneotype and clinical feature
    Atlas Genet Cytogenet Oncol Haematol. in press
    On line version : http://AtlasGeneticsOncology.org/Deep/BNHLclassifID20012.htm
    History of this paper:
    Gisselsson, D. Chromosomal instability in cancer: Causes, consequences. Atlas Genet Cytogenet Oncol Haematol. 2001;5(3):236-243.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37771/05-2001-ChromosomInstabilID20023.pdf

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Mon Sep 18 17:22:06 CEST 2017


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