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

Identity

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) ID1050> or variants / R earr (80% of the cases) GENES

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) ID: 2022> / 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 GENES

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Contributor(s)

Written	02-2000	Antonio Cuneo

Citation

This paper should be referenced as such :

Cuneo A . Classification of B-cell non-Hodgkin lymphomas (NHL). Atlas Genet Cytogenet Oncol Haematol. February 2000 . URL : http://AtlasGeneticsOncology.org/Genes/BNHLClassifID2067.html

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