Review on Small lymphocytic lymphoma, with data on clinics, and the genes involved

Castoldi, GL

Cuneo, A

Atlas of Genetics and Cytogenetics in Oncology and Haematology

I-Revues

   
 
 
 
 
 
Leukaemia Section 
Mini Review 
 
Atlas Genet Cytogenet Oncol Haematol. 2000; 4(2)  
 
86 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology 
OPEN ACCESS JOURNAL AT INIST-CNRS 
Small lymphocytic lymphoma 
Antonio Cuneo, Gian Luigi Castoldi 
Hematology Section, Department of Biomedical Sciences, University of Ferrara, Corso Giovecca 203, 
Ferrara, Italy (AC) 
 
Published in Atlas Database: May 2000 
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/SLLID2073.html 
DOI: 10.4267/2042/37626 
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. 
© 2000 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
Clinics and pathology 
Disease 
Small lymphocytic lymphoma (SLL) represents the 
lymphomatous counterpart of B-cell chronic 
lymphocytic leukemia. 
Phenotype/cell stem origin 
The typical cases have faint surface IgM/IgD 
expression with k/l light chain restriction; pan-B 
antigens are positive, but CD22 expression is weak. 
CD5 and CD23 test positive, whereas CD10 and FMC7 
are negative; the expression of CD11c and CD25 is 
variable; the postulated normal counterpart is a 
peripheral CD5+/CD23+ B cell; based on the 
presence/absence of the CD38 antigen, a distinction 
was suggested for CLL, that may potentially apply also 
to SLL, between virgin B-cells that have not 
encoutered the antigen and cells harbouring somatic 
hypermutation of the Ig-gene variable region, 
corresponding to post-germinal memory-B cells. 
Epidemiology 
Accounts for 5-10% of NHL. 
Clinics 
The disease usually presents with bone marrow and 
peripheral blood (PB) involvement and typically runs 
an indolent course; transformation into diffuse large 
cell lymphoma (Richter's syndrome) may occur. 
Pathology 
Enlarged lymph nodes show an infiltrate consisting of a
majority of small lymphocytes with clumped chromatin 
and inconspicuous nucleolus; larger cells 
(prolymphocytes and paraimmunoblasts) are also 
present, usually clustered in pseudo-follicles, referred 
to as "proliferation centres"; in some cases having the 
histologic features of SLL, the cells may have 
plasmacytoid differentiation with cytoplasmic Ig and a 
paraprotein (monoclonal component) may be found in 
the serum; plasmacytoid differentiation, corresponding 
to many cases included in the category 
"immunocytoma, lymphoplasmacytoid type" in the 
Kiel classsification does not constitute at the present 
time an indication of a different disease and should not 
be confused with the "lymphoplasmacytoid 
lymphoma", corresponding to most cases of 
Waldenstrom's macroglobulinemia, the prognostic 
impact of plasmacytic differentiation in SLL remains a 
subject for research. 
Cytogenetics 
Note 
- Relatively few studies were performed on lymph node 
material; though it is reasonable to assume that a 
similar profile of molecular cytogenetic lesions may 
characterize SLL and CLL no formal proof that this is 
really the case was provided; data here summarized 
refer to those cases diagnosed as SLL and do not take 
into account the data described in CLL.  
- A chromosome anomaly was detected by cytogenetics 
in 60-90% of the cases. 
Cytogenetics morphological 
Trisomy 12 was seen in 10-30% of the cases and other
trisomies, involving chromosomes 3 (+3) and 18 (+18) 
in approximately 10% of the cases; 
Deletions/translocations 6q21-23 were detected in 15-
25% of the cases and they showed a correlation with 
leukemic involvement by large prolymphocytoid cells; 
Structural changes of 11q, mostly deletions involving 
the q22-23 segment (del(11q)) were detected in 10-
20% of the cases and structural anomalies of 12p13 in 
10% of the cases in one study; 
Small lymphocytic lymphoma Cuneo A, Castoldi GL 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2000; 4(2)  
 
87 
The t(14;19)(q32;q13.3), deletions/translocations 
14q22 and the t(11,14)(q13;q32) were reported in 
several cases; other chromosome 14q32 translocations 
with 1p32 and other unknown partners may be found in 
SLL; in general, those cases with a 14q anomaly 
require a precise histologic characterization because 
their distinction from mantle cell lymphomas and 
marginal zone B-cell lymphomas may pose difficult 
diagnostic problems; 
FISH studies found an approximate 50% incidence for 
cryptic 13q14 deletions and a 5-10% incidence for 
17p13 deletions (advanced disease). 
Cytogenetics molecular 
Molecular cytogenetic lesions and methods for 
detection: the following associations were proposed: 
6q21-q23: loss of a putative oncosuppressor gene; 
detection by FISH with 6q21 probe, CGH and LOH 
studies; 
11q deletions: no study was specifically devoted to 
SLL; in CLL, ATM gene deletion with postulated loss 
of function in some cases; the most sensitive mean for 
detection is FISH with ATM-probes; SSCP and 
sequencing of exons with altered motility can be usd 
for the demonstration of lesions of the remaining ATM 
allele; 
13q14 deletions: putative oncosuppressor gene. FISH 
with probes mapping between the Rb and the D13S25 
marker are ideal for the detection of small deletions. 
CGH is less sensitive; 
17p13 deletions: loss of p53 function; detection is 
usually achieved by FISH with a p53 probe and SSCP 
and sequencing of exons with altered motility for the 
demonstration of lesions of the remaining allele; 
t(14;19): fusion of IgH and BCL3 (transcription factor); 
the translocation exchanges chromosome bands similar 
in size and banding pattern; FISH with chromosome 
painting is useful; southern blotting detects most BCL3 
rearrangements; 
t(11;14)(q13;q32): fusion of IgH and BCL1/CCND1 
(cyclin); dual-color FISH with BCL1 and IgH probes or 
with probes proximal and distal to the BCL1 locus. 
PCR and southern blotting have limited application due 
to variability of the breakpoint location. 
References 
Offit K, Parsa NZ, Gaidano G, Filippa DA, Louie D, Pan D, 
Jhanwar SC, Dalla-Favera R, Chaganti RS. 6q deletions define 
distinct clinico-pathologic subsets of non-Hodgkin's lymphoma. 
Blood. 1993 Oct 1;82(7):2157-62 
Richardson C, Ward M, Podda S, Bank A. Mouse fetal liver 
cells lack functional amphotropic retroviral receptors. Blood. 
1994 Jul 15;84(2):433-9 
Whang Peng J, Knutsen T. Cytogenetics of non-Hodgkin's 
lymphomas. Magrath I (ed). The non-Hodgkin’s lymphomas, 
pp. 277-303; Arnold, London 1997. 
Ong ST, Le Beau MM. Chromosomal abnormalities and 
molecular genetics of non-Hodgkin's lymphoma. Semin Oncol. 
1998 Aug;25(4):447-60 
Cuneo A, Bigoni R, Rigolin GM, Roberti MG, Bardi A, 
Campioni D, Minotto C, Agostini P, Milani R, Bullrich F, Negrini 
M, Croce C, Castoldi G. 13q14 deletion in non-Hodgkin's 
lymphoma: correlation with clinicopathologic features. 
Haematologica. 1999 Jul;84(7):589-93 
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink 
HK, Vardiman J, Lister TA, Bloomfield CD. 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. J Clin Oncol. 1999 Dec;17(12):3835-49 
Küppers R, Klein U, Hansmann ML, Rajewsky K. Cellular 
origin of human B-cell lymphomas. N Engl J Med. 1999 Nov 
11;341(20):1520-9 
Zhang Y, Matthiesen P, Harder S, Siebert R, Castoldi G, 
Calasanz MJ, Wong KF, Rosenwald A, Ott G, Atkin NB, 
Schlegelberger B. A 3-cM commonly deleted region in 6q21 in 
leukemias and lymphomas delineated by fluorescence in situ 
hybridization. Genes Chromosomes Cancer. 2000 
Jan;27(1):52-8 
This article should be referenced as such: 
Cuneo A, Castoldi GL. Small lymphocytic lymphoma. Atlas 
Genet Cytogenet Oncol Haematol. 2000; 4(2):86-87. 


Small lymphocytic lymphoma

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