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

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

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

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Written	2000-02	Antonio Cuneo
		Section, Dept. Of Biomedical Sciences, University of Ferrara, 44100 Ferrara Italy
Updated	2001-05	David 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