Diffuse large B cell lymphoma

Diffuse large B-cell lymphoma

 

Clinical features

§   40% initially confined to extranodal sites

§   Rapidly enlarging , often symptomatic mass

 

Aetiology

§   Immunodeficiency is a risk factor

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

 

Morphology

§   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

 

Immuno

§   Pan B-markers

§   Surface and cytoplasmic Ig may be positive

§   CD30 negative, except for anaplastic

§   High proliferation rate (>40%)

 

Cytogenetics

§        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

Score

CR%

5 Yr survival

Age >60             

0-1 = low risk

87

73

ECOF Performance S >2

2 = intermediate risk

67

51

LDH >N

3 = high- intermediate risk

55

43

Extranodal sites >1

>4 = high risk

44

26

Stage ¾

 

 

 

 

Other risk factors

§        Poor

§        High proliferative rate – Ki67 marker of high proliferation

§        Bcl-2

§        P53

§        Good

§        Bcl-6

 

 

Treatment

§        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

 

Morphology

§   Massive diffuse proliferation associated with  compartmentalising fibrosis

 

Immunophenotyp

§   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

 

Treatment

§   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

 

Morphology

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

§   Express B-cell markers

 

Treatment

§   Poor prognosis partly related to delays in diagnosis

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