Classification of B-cell non-Hodgkin's lymphomas (NHL) : cytogenetic entities, immunopheneotype and clinical features
2000-02-01 AffiliationAntonio 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 [email protected]
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) |
| ||
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) |
| ||
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) |
| ||
Diffuse large cell lymphoma CD19+; CD22+; CD10-/+; SIg+ | Large transformed B-cells harbouring somatic hypermutation of the Ig genes (ongoing mutations in some cases) |
|
| ||
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 / |
| ||
Burkitt-like lymphoma Pan-B+; TdT-; CD10-/+ CD5-; sIg+ | Peripheral B-cells that have encountered the antigen |
| |||
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) |
| ||
| 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.
| Bibliography |
| Cytogenetic profile of lymphoma of follicle mantle lineage: correlation with clinicobiologic features. |
| Cuneo A, Bigoni R, Rigolin GM, Roberti MG, Bardi A, Piva N, Milani R, Bullrich F, Veronese ML, Croce C, Birg F, Döhner H, Hagemeijer A, Castoldi G |
| Blood. 1999 ; 93 (4) : 1372-1380. |
| PMID 9949181 |
| The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas. |
| Dierlamm J, Baens M, Wlodarska I, Stefanova-Ouzounova M, Hernandez JM, Hossfeld DK, De Wolf-Peeters C, Hagemeijer A, Van den Berghe H, Marynen P |
| Blood. 1999 ; 93 (11) : 3601-3609. |
| PMID 10339464 |
| World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. |
| Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD |
| Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (12) : 3835-3849. |
| PMID 10577857 |
| Correlation of bcl-2 rearrangement with clinical characteristics and outcome in indolent follicular lymphoma. |
| López-Guillermo A, Cabanillas F, McDonnell TI, McLaughlin P, Smith T, Pugh W, Hagemeister F, Rodríguez MA, Romaguera JE, Younes A, Sarris AH, Preti HA, Lee MS |
| Blood. 1999 ; 93 (9) : 3081-3087. |
| PMID 10216105 |
| Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. |
| Kramer MH, Hermans J, Wijburg E, Philippo K, Geelen E, van Krieken JH, de Jong D, Maartense E, Schuuring E, Kluin PM |
| Blood. 1998 ; 92 (9) : 3152-3162. |
| PMID 9787151 |
| Cellular origin of human B-cell lymphomas. |
| Küppers R, Klein U, Hansmann ML, Rajewsky K |
| The New England journal of medicine. 1999 ; 341 (20) : 1520-1529. |
| PMID 10559454 |
| Small noncleaved, non-Burkitt's (Burkit-Like) lymphoma: cytogenetics predict outcome and reflect clinical presentation. |
| Macpherson N, Lesack D, Klasa R, Horsman D, Connors JM, Barnett M, Gascoyne RD |
| Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (5) : 1558-1567. |
| PMID 10334544 |
| t(9;14)(p13;q32) denotes a subset of low-grade non-Hodgkin's lymphoma with plasmacytoid differentiation. |
| Offit K, Parsa NZ, Filippa D, Jhanwar SC, Chaganti RS |
| Blood. 1992 ; 80 (10) : 2594-2599. |
| PMID 1384792 |
| Genetics of small lymphocyte disorders. |
| Panayiotidis P, Kotsi P |
| Seminars in hematology. 1999 ; 36 (2) : 171-177. |
| PMID 10319386 |
| Prognostic value of chromosomal abnormalities in follicular lymphoma. |
| Tilly H, Rossi A, Stamatoullas A, Lenormand B, Bigorgne C, Kunlin A, Monconduit M, Bastard C |
| Blood. 1994 ; 84 (4) : 1043-1049. |
| PMID 8049424 |
| Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. |
| Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer MJ |
| Cell. 1999 ; 96 (1) : 35-45. |
| PMID 9989495 |
| 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 |
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Citation
Classification of B-cell non-Hodgkin's lymphomas (NHL) : cytogenetic entities, immunopheneotype and clinical features
Atlas Genet Cytogenet Oncol Haematol. 2000-02-01
