Guidelines on Diagnosis and Treatment of Malignant Lymphomas

Diffuse Large B-Cell Lymphoma
Definition and Incidence
Diffuse large B-cell lymphoma (DLBCL) is composed of
B lymphoid cells with nuclear size equal to or exceeding
macrophage nuclei or more than twice the size of a normal
lymphocyte. DLBCL accounts for about 30% of cases of non-
Hodgkin Lymphoma with an incidence of 4 cases/ 100,000/ year.
The incidence increases with age from 0.3 at 35-39 years to
26.6 at 80-84 years. The median age of diagnosis is 64 years
with an equal sex ratio. In recent decades the incidence has
been increasing independent of HIV infection as a risk factor.
ICD – O Code: 9680/3
Clinical Presentation
DLBCL can present with nodal or extranodal disease, with up to
40% of cases presenting with extranodal disease. The most
common extranodal site is the gastrointestinal tract (mainly
stomach and ileocaecal region) but the disease can present at
virtually any location including skin, central nervous system
(CNS), bone, testis, soft tissue, salivary gland, female genital
tract, lung, kidney, liver, Waldeyer’s ring and spleen. Primary
presentation with bone marrow or peripheral blood involvement is
rare. Primary mediastinal large B-cell lymphoma differs in that the
disease is limited to the mediastinum and is seen more frequently
in women between 20-40 years. Patients typically present with a
single, rapidly enlarging mass which on staging may be more
disseminated. Transformed DLBCL following an indolent
lymphoma such as chronic lymphocytic leukaemia/ small
lymphoctic lymphoma (CLL/SLL), follicular lymphoma, marginal
zone B-cell lymphoma or lymphocyte predominant Hodgkin
lymphoma is well described. Underlying immunodeficiency and
auto-immune diseases are significant risk factors and are
frequently associated with Epstein-Barr virus (EBV) positivity.
DLBCL replaces the normal architecture of the lymph node or
tissue of origin diffusely, though the infiltration can be partial,
inter-follicular or rarely sinusoidal. The perinodal soft tissues are
often infiltrated. DLBCLs are morphologically diverse including a
number of specific subtypes and specific entities (see below) and
a large number of cases which are grouped together as DLBCL
not otherwise specified (NOS). DLBCL NOS includes the
common morphologic variants centroblastic, immunoblastic and
anaplastic in addition to rare morphologic variants. DLBCL NOS
can also be divided into subgroups based on immunophenotype
(CD5+, Germinal centre B cell-like (GCB), non-GCB) or based
on gene expression profile (Germinal center B cell-like (GCB)
and activated B cell-like (ABC)) although use of these subgroups
to determine therapy is not currently recommended.
Specific subtypes of DLBCL include T cell/histiocyte rich DLBCL,
Primary CNS DLBCL, Primary cutaneous DLBCL (leg type) and
EBV positive DLBCL of the elderly.
Specific DLBCLs with characteristic clinicopathological features
include Primary mediastinal large B cell lymphoma, Intravascular
large B cell lymphoma, DLBCL associated with chronic
inflammation, Lymphomatoid Granulomatosis, ALK-positive large
B cell lymphoma, Plasmablastic lymphoma, Primary effusion
lymphoma and Large B cell lymphoma arising in HHV-8
associated Castleman’s disease.
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