Diffuse large B cell lymphoma

Diffuse large B-cell lymphoma


Clinical features

§   40% initially confined to extranodal sites

§   Rapidly enlarging , often symptomatic mass



§   Immunodeficiency is a risk factor

§   DLBCL in immunodeficiency are more often EBV positive than in sporadic DLBCL



§   Architecture is replaced

§   Peri-nodal soft tissue is infiltrated

§   Large transformed lymphoid cells

§   Morphologic variants

o        Centroblastic

o        Immunoblastic

o        T-cell/  histiocyte rich

o        Anaplastic



§   Pan B-markers

§   Surface and cytoplasmic Ig may be positive

§   CD30 negative, except for anaplastic

§   High proliferation rate (>40%)



§        Microarray technology can divide into

§        Germinal centre B cell like – better prognosis

§        Activated B cell like

§        Type 3


Ann Arbor 

Stage 1 : 1 LN region or 1 extralymphatic site

Stage 2 : 2 or more LN sites on same side of diaphragm or contiguous involvement of 1 extralymphatic site and LN

Stage 3 : LNs on both sides of diaphragm, may include spleen

Stage 4 : Extranodal sites


A : no systemic symptoms

B  : systemic symptoms

E : sinlge extranodal site

S : splenic involvement

X : Bulky disease >1/3 widening of mediastinum at T5-6, nodal mass >10cm


International Prognostic Index

IPI factor



5 Yr survival

Age >60             

0-1 = low risk



ECOF Performance S >2

2 = intermediate risk




3 = high- intermediate risk



Extranodal sites >1

>4 = high risk



Stage ¾





Other risk factors

§        Poor

§        High proliferative rate – Ki67 marker of high proliferation

§        Bcl-2

§        P53

§        Good

§        Bcl-6




§        Depends on stage of disease

Stage I

§        3 cycles R CHOP

§        Followed by involved field radiotherapy


Stage II-IV

§        R-CHOP currently standard treatment

§        Rituximab binds CD20 and may work in part by down regulating BCL2


Relapsed/ refactory

§        Long term overall survival <10%

§        Second line chemo DHAP / ICE / EPOCH

§        Auto-SCT – high dose therapy followed by auto is effective only in those who have shown some response to conventional dose second line chemo prior to auto

§        Allo

§        Y90 labelled monoclonal antibody therapy


Assessment of response

§        PET

§        Negativity after 2-4 cycles strongly correlates with durable remission

§        Positive patients have a high likelihood of relapse – consider for high dose therapy

§        Follow up

§        3 monthly follow up (FBC / LDH) for the 1st 2-3 years with 6 monthly CT scans

§        Years 4/5 – 6 monthly follow up

§        Annual follow up thereafter

Mediastinal (thymic) large B-cell lymphoma


Subtype of DLBCL arising in the mediastinum


Clinical Features

§   More common in women age 20-40

§   Signs and symptoms secondary to a large anterior mediastinal mass

§   May have impending SVC obstruction

§   Progresses to involve, kidneys, ovaries, liver, spleen and CNS

§   EBV is not present



§   Massive diffuse proliferation associated with  compartmentalising fibrosis



§   Pan B-markers

§   Lack surface Ig

§   May mimic Hodgkins with interspersed  lymphocytes and eosinophils but this expresses CD45 in contrast to classical HD

§   Recent gene expression profiling shows that it is distinct from DLBCL and shares many components with Hodkin Reed-Sternberg cells



§   R CHOP usually followed by involved field radiotherapy

§   Prognosis largely dependant on stage of disease at presentation

§   PET currently under evaluation to distinguish residual disease from fibrosis




Intravascular large B cell lymphoma


Subtype of DLBCL – lymphoma cells only in the lumina of small vessels


Sites of involvement

§   Usually widely disseminated at diagnosis


Clinical Features

§   Symptoms result from occlusion of small vessels by tumour cells

§   May have B-symptoms



§   Neoplastic cells lodged in lumina of small vessels, may be fibrin thrombi

§   Express B-cell markers



§   Poor prognosis partly related to delays in diagnosis