Primary DLBCL of the central nervous system (DLBCL-CNS) is an aggressive B-cell neoplasm due in part to the intra-cerebral and/or intra-ocular location, and because a high percentage of cases are in the activated B cell like (ABC) subtype. Lymphoproliferative diseases of the central nervous system are rare, diagnostics and treatment are accordingly challenging. The special localization is related with a series of newly recognized genetic, genomic and immunologic features directing to the stron

Chen, Ding-Bao

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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 Leukaemia Section 
Review 
Atlas Genet Cytogenet Oncol Haematol. 2018; 22(10) 446 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology 
OPEN ACCESS JOURNAL AT INIST-CNRS 
Primary DLBCL of the central nervous system 
(CNS) 
Ding-Bao Chen 
Department of Pathology, Peking University People's Hospital, Beijing 100044, People's Republic of 
China; cdingbao@163.com 
Published in Atlas Database: September 2017 
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/DLBCLPrimCNSID2154.html 
Printable original version : http://documents.irevues.inist.fr/bitstream/handle/2042/68951/09-2017-DLBCLPrimCNSID2154.pdf 
DOI: 10.4267/2042/68951
This article is an update of : 
DLBCLPrimCNSID2154. Atlas Genet Cytogenet Oncol Haematol 
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. 
© 2018 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
Abstract 
Primary DLBCL of the central nervous system 
(DLBCL-CNS) is an aggressive B-cell neoplasm due 
in part to the intra-cerebral and/or intra-ocular 
location, and because a high percentage of cases are 
in the activated B cell like (ABC) subtype. 
Lymphoproliferative diseases of the central nervous 
system are rare, diagnostics and treatment are 
accordingly challenging. The special localization is 
related with a series of newly recognized genetic, 
genomic and immunologic features directing to the 
strong interaction between transformed lymphoma 
cells, neural tissue components and the local immune 
response. Here the clinicopathological of DLBCL-
CNS will be discussed. 
KEYWORDS 
Diffuse large B-cell lymphoma; Central nervous 
system 
Identity 
Other names 
Primary CNS lymphoma; primary intraocular 
lymphoma 
Clinics and pathology 
Disease 
DLBCL-CNS are all primary intracerebral or 
intraocular lymphomas. Lymphomas of the dura, 
intravascular large B-cell lymphoma, lymphoma 
with evidence of systemic disease or secondary 
lymphomas, and all immunodeficiency-associated 
lymphomas are excluded (Swerdlow, et al ,2008). 
Phenotype/cell stem origin 
Expression or absence of chemokines and 
chemokine receptors or cytokines may contribute to 
the specific location of DLBCL-CNS. Tumor cells 
and endothelial cells may interact via activation of 
IL4 to creats a favourable microenvironment for 
tumor growth. DLBCL-CNS show a restricted 
homing to the main immune sanctuaries (brain, eyes 
and testis) (Swerdlow, et al ,2008). DLBCL-CNS 
expresses CD20. CD22 or CD79a. CD10 expresses 
in about 10-20% cases, whereas bcl6 in 60-80% and 
IRF4/MUM1 in 90%. Approximately 90% of cases 
show a non-germinal center immunophenotype 
(CD10-, Bcl6+/-, MUM1+) (Swerdlow, et al ,2008. 
Bacon, et al.2009). 
Epidemiology 
The incidence of DLBCL-CNS has been increasing 
and it accounts for 4% of primary brain tumors and 
only 2-4 % of intracranial neoplasms. The median 
Primary DLBCL of the central nervous system 
(CNS) 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2018; 22(10) 447 
 
age is approximately 60 years, and there is a slight 
preponderance of male patients (Swerdlow, et al 
,2008. Patrick, 2015). 
Clinics 
DLBCL-CNS commonly presents with either focal 
neurological deficits (50-80%) or progressive 
neurocognitive dysfunction (20-30%). In patients 
who present with acute neurological symptoms, a 
noncontrast head CT can be unremarkable, and 
occasionally, hypodense areas can be mistaken for 
ischemia. The diagnosis of PCNSL is usually not 
entertained until a contrast- enhanced MRI is 
performed and reveals a homogenously enhancing 
mass in the deep white matter or corpus callosum. 
Typical radiologic features include lesion location 
adjacent to the cerebrospinal fluid (CSF) space 
(Swerdlow, et al ,2008. Ferry , 2008. Bacon, et 
al.2009). 
Pathology 
Morphologically, CNS-DLBCL are diffuse 
infiltrates of centroblasts or immunoblasts, with a 
tendency to cluster around cerebral blood vessels, 
often accompanied by small reactive T cells and 
reactive accessory cells. There is often marked 
tumour necrosis, especially following the 
administration of corticosteroids. The Ki67-
proliferation fraction is typically high. NS-DLBCL 
presenting in immunosuppressed individuals is often 
EBV-positive. CNS-DLBCL must be differentiated 
from secondary CNS involvement by systemic 
DLBCL, for which the involvement of multiple 
extranodal sites or specific extranodal sites such as 
the testis and sino-nasal cavity is a risk factor. 
 
Figure 1.  Primary DLBCL-CNS of the sphenoid sinus. Diffuse proliferation of lymphoid cells can be seen 
between fat cells. Some cells accumulate in the perivascular space. (HE staining). 
 
Figure 2.  The lymphoid cells are medium to large in size, with oval nuclei and indistinct nucleoli.some 
accumulation in the perivascular space. (HE staining). 
Primary DLBCL of the central nervous system 
(CNS) 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2018; 22(10) 448 
 
 
Figure 3.  The cells are positive for CD20. 
 
Treatment 
Although treatment with radiotherapy alone leads to 
an initial response, disease recurrence is higher when 
compared to extranodal systemic non- Hodgkin 
lymphoma .CHOP produces notable imaging 
responses but no durable disease control .High-dose 
methotrexate chemotherapy followed by whole brain 
radiation therapy is regarded as the standard therapy 
with a response rate of 35-65% (Swerdlow, et al 
,2008. Patrick, 2015). 
Prognosis 
Despite recent advances in treatment and significant 
improvement in complete remission rates, 35-60 % 
of PCNSL patients will relapse, usually within the 
first 2 years from diagnosis; 10-15 % will be 
refractory to treatment. In primary DLBCL-CNS, 
there was no significant difference in median overall 
survival (OS) between the wild type and mutated 
MYD88 cases, or between methylated and 
unmethylated MGMT cases. However, a significant 
difference was noted in median OS between the wild 
type and mutated CD79B cases (Zheng, et al, 2017. 
Swerdlow, et al ,2008. Patrick, 2015). 
Cytogenetics 
Note 
The most frequent genomic aberration of DLBCL-
CNS is the deletion of 6p21.3 leading to loss of HLA 
genes. Complimentary DNA microarray analysis in 
DLBCL-CNS demonstrates higher expression of 
interleukin-4 (IL4) and X-box binding protein 1 ( 
XBP1) compared to DLBLC of other sites. 
(Rubenstein ,et al. 2006). Alterations in 
BCR/TLR/NF-kb pathways are seen in greater than 
90 % of DLBCL-CNS, thereby involving pathways 
in proliferation, apoptosis, and lymphocyte 
proliferation. (Braggio ,et al. 2015)The MYD88 
L265P activating mutation appears to be a common 
molecular aberration in up to 50 % of patients, and 
although no impact on clinical outcome has been 
demonstrated, it may be an important therapeutic 
target with Bruton tyrosine kinase inhibitors such as 
ibrutinib currently in clinical trials (Gonzalez-
Aguilar, et al.2012. Swerdlow, et al ,2008. Bacon, et 
al.2009). 
References 
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histopathology, 2009,16(2):82-98. 
Braggio E, Van Wier S, Ojha J, et al.. Genome-wide 
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Fukumura K, Kawazu M, Kojima S, et al.. Genomic 
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Primary DLBCL of the central nervous system 
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Atlas Genet Cytogenet Oncol Haematol. 2018; 22(10) 449 
 
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This article should be referenced as such: 
Chen DB. Primary DLBCL of the central nervous 
system (CNS). Atlas Genet Cytogenet Oncol 
Haematol. 2018; 22(10):446-449. 


Primary DLBCL of the central nervous system (CNS)

http://documents.irevues.inist.fr/bitstream/2042/68951/1/09-2017-DLBCLPrimCNSID2154.pdf

Primary DLBCL of the central nervous system (CNS)

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