Classification of B-cell chronic lymphoproliferative disorders (CLD)

2000-02-01   Antonio Cuneo 

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

Clinics and Pathology

Disease

Chronic lymphocytic leukemia CD5+ B cell that has encountered the antigen and harbours hypermutated IgV genes

Phenotype stem cell origin

CD5+; CD23+; CD38+/-; CD22 weak+; FMC7-; sIg+ weak , 
  • Pan-B+; CD5-/+; CD23-/+; CD11c+/-; CD25-/+; FMC7+/-; sIg+ bright
  • Cytogenetics

    del(13q) (10-15% of the cases): Typical morphology; indolent disease; favourable prognosis if present as the sole change (Note: typical morphology (FAB criteria): more than 90% of neoplastic cells are represented by small lymphocytes (diameter less than 14 m, i.e. < two red blood cells); atypical morphology: 10-55% of the lymphocytes are larger than 14 m with few prolymphocytes (CLL mixed-cell type); the cases are usually referred to as CLL/PL if prolymphocytes predominate among large lymphoid cells; PLL: more than 55%, and usually >70% of the cells are prolymphocytes.) , 
  • (20-40% of cases) with or without +3 , 
  • t(11;14)(q13;q32) ( involved, mainly in the MTC and mTC1)(<5% of the cases): Rare cases of CLL/PL, transforming into prolymphocytic leukemia; Primary blood and marrow involvement, usually with splenomegaly, without adenopathy
  • Disease

    Chronic lymphocytic leukemia CD5+ virgin recirculating B-cell with germline IgV genes

    Phenotype stem cell origin

    CD5+; CD23+; CD38-/+; CD22 weak+; FMC7-; sIg+ weak

    Cytogenetics

    +12 (10-15% of the cases): Frequent atypical morphology; relatively indolent disease; unfavourable prognosis as compared with other single chromosome aberrations, but not against complex karyotypes, 11q- or 17p-.

    Disease

    Chronic lymphocytic leukemia CD5+ recirculating B-cell

    Phenotype stem cell origin

    CD5+; CD23+; CD22 weak+; FMC7-; sIg+ weak

    Cytogenetics

  • (20% of the cases) (breaks outside the MTC and mTC1 of BCL1)
  • Phenotype stem cell origin

    Peripheral B-lymphocyte that has encountered the antigen and harbours hypermutated IgV genes

    Clinics

    Rare and aggressive disease with a majority of relatively large lymphocytes with round nucleus and a prominent central nucleolus

    Cytogenetics

    t(11;14)(q13;q32) (BCL1 involved in the MTC and mTC1)

    Phenotype stem cell origin

  • Marginal zone lymphocytes harbouring hypermutated IgV genes
  • Clinics

    Indolent disease; There are not establisehd correlations between chromosome lesions and hematologic features; Cases with t(11;14) showed frequent CD5-positivity and featured an indolent course

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    Summary

    Note

  • A classification of chronic (mature) B-cell lymphoproliferative disorders based on reproducible morphologic and immunologic criteria was proposed by the FAB group in 1989. Ever since a number of cytogenetic studies disclosed a remarkable degree of heterogeneity within each disease category. Herein, the main cytogenetic entities of chronic lymphocytic leukemia and related disorders, B-cell prolymphocytic leukemia, splenic lymphoma with villous lymphocytes are presented.
  • Other disease subsets of B-cell CLD include the leukemic phase of follicle centre cell lymphoma, mantle cell lymphoma and lymphoplasmacytic lymphoma. The cytogenetic features of these forms of leukemic lymphoma are the described in the B-NHL classification
  • Comment: The incidence for each of these chromosome lesions (below) is higher when investigated by the more sensitive fluorescence in situ hybridization (FISH) technique: FISH detected 13q14 deletions in 40-50% of the cases, +12 in 15-20% of the cases; 11q22-23 deletions in 7-10% of the cases; 17p13 deletions in 15-20% of the cases. The prognostic significance for each of these anomalies, 11q- excluded, mainly derives from studies that used conventional cytogenetics and needs to be reassessed in the light of the more recent data provided by FISH analysis.
  • 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. MTC and mTC1: major translocation cluster and minor translocation cluster 1 of BCL1 region, respectively.
  • Citation

    Antonio Cuneo

    Classification of B-cell chronic lymphoproliferative disorders (CLD)

    Atlas Genet Cytogenet Oncol Haematol. 2000-02-01

    Online version: http://atlasgeneticsoncology.org/haematological/2072/bcldclassifid2072

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