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

2000-02-01   Antonio Cuneo 

1.Hematology Section, Dept. Of Biomedical Sciences, University of Ferrara, 44100 Ferrara Italy

Clinics and Pathology

Phenotype stem cell 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) , 
  • Putative cell of origin: Peripheral B-lymphocyte transforming into plasma cell with mutated IgV genes and ongoing mutations , 
  • Putative cell of origin: Centrocytes / centroblasts of germinal centre origin with somatic hypermutation of the IgV genes and ongoing mutations (antigen driven stimulation) , 
  • Putative cell of origin: Large transformed B-cells harbouring somatic hypermutation of the Ig genes (ongoing mutations in some cases) , 
  • Putative cell of origin: Peripheral B-cells that have encountered the antigen and harbours somatic hypermutation of the Ig genes , 
  • Putative cell of origin: Peripheral B-cells that have encountered the antigen , 
  • Putative cell of origin: CD5+ B-cells of the follicle mantle having germline IgV gene sequences , 
  • Putative cell of origin: Marginal zone lymphocytes harbouring hypermutated IgV genes
  • Clinics

  • Indolent disease;
  • leukemic involvement by lymphoid cells, including prolymphocytes and/or paraimmunoblasts Splenomegaly , 
  • Conflicting data as to the prognostic significance of the t(14;18)/BCL2 , 
  • 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 , 
  • Specific treatment mandatory , 
  • Cases with dual 8;14 and 14;18 translocations have a worse outcome (data requiring confirmation -1 study only) , 
  • Response to chemotherapy often unsatisfactory , 
  • Short survival , 
  • Complex karyotype carries an unfavourable prognostic significance
  • Cytogenetics

    del(6)(q21-23) (20-30% 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) , 
  • t(8;14)+ t(14;18) (30% of cases) , 
  • 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
  • Phenotype stem cell origin

  • Histologic subset and Immunophenotype: Pan-B+; CD5-; CD10-; cyIgM+
  • Clinics

    Indolent low-grade disease, with possible clinical and/or histologic progression

    Cytogenetics

  • t(9;14)(p13;q32) PAX5/IgH (50% of cases)
  • Phenotype stem cell origin

  • Histologic subset and Immunophenotype: Pan-B+; CD10+/-; CD5-; sIg+
  • Clinics

  • Indolent. Advanced stages predominate.
  • Cytogenetics

  • t(14;18)(q32;q21) / BCL2 Rearr (70-80% of cases)
  • Phenotype stem cell origin

  • Histologic subset and Immunophenotype: CD19+; CD22+; CD10-/+; SIg+
  • Clinics

  • Usually aggressive
  • Cytogenetics

  • t(14;18) and p53 mutations (20% of the cases)
  • Phenotype stem cell origin

  • Histologic subset and Immunophenotype: Pan-B+; TdT-; CD10+; CD5-; sIgM+
  • Clinics

  • Extremely aggressive disease
  • Cytogenetics

  • t(8;14)(q24;q32) or variants / c-MYC R earr (80% of the cases)
  • Phenotype stem cell origin

  • Histologic subset and Immunophenotype: Pan-B+; TdT-; CD10-/+ CD5-; sIg+
  • Clinics

  • Aggressive disease
  • Cytogenetics

  • t(8;14) or variants (25% of cases)
  • Phenotype stem cell origin

  • Histologic subset and Immunophenotype: Pan-B +; CD5+; CD23-; CD10-/+; sIgM+ bright
  • Clinics

  • Advanced stages predominate
  • 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)
  • Phenotype stem cell origin

  • Histologic subset and Immunophenotype: pan-B+; CD5-/+; CD10-; CD23-; CD11c+/-; cyIg + (40% of the cells), sIgM+ bright; sIgD-)
  • Cytogenetics

  • t(11;18)(q21;q21) / PI2 / MLT fusion (30-50% of the low-grade MALT): Extra-nodal low-grade MALT lymphoma; indolent disease
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    Summary

    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.

    Citation

    Antonio Cuneo

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

    Atlas Genet Cytogenet Oncol Haematol. 2000-02-01

    Online version: http://atlasgeneticsoncology.org/haematological/2067/bnhlclassifid2067

    External Links