Infection associated lymphoma

Are MALT - mucosal associated lymphoid tissue palpable nodes?

No

Example of agent that cause infection associated lymphomas

1. Directly oncogenic - infect a subset of lymphocytes in which they express viral products that act as oncogenes

Epstein Barr virus EBV

Human herpes virus 8 HHV8

Human T-lymphotropic virus 1HTLV1

EBV

• Burkitt lymphoma 

• Post-transplant lymphoproliferative disease

• Hodgkin disease (early age)

• Extranodal NK/T cell lymphoma

HHV8 

• Primary effusion lymphoma

HTLV1

• Adult T-cell leukaemia/ lymphoma

Agents that cause infection associated lymphomas

Indirectly oncogenic - directly infect lymphocytes but persist in tissues and trigger a lymphocytic proliferation that is primary reactive but might escape regulation 

• Helicobacter pylori 

• Campylobacter pylori 

• Hepatitis C virus 

• Helicobacter pylori - Gastric lymphoma 

• Campylobacter pylori - Bowel lymphoma

• Hepatitis C virus 

- Marginal zone lymphoma; nodal and splenic

Lymphoplasmacytic lymphoma

Diffuse large B cell lymphoma 

(liver cancer) 

EBV infection in the immunocompetent host 

85-90% population are EBV positive

Typically transmitted through contact via saliva of a carrier

Enters the nasopharyngeal tract and infects epithelial cell 

Establish a lytic infection which infects the tonsillar B cells.

Infected B cells are kept from prolierating by CTL

LYTIC → LATENT

EBV estabilishes a latent infection which it remains as an episome in a subset of resting memory B cells

What is infectious mononucleosis?

Initiation of EBV infection - EBV establishes a lytic infection which is associated with the production of new viral particles that can infect naive tonsillar B cells and transmit the virus to other individuals

Oncogenicity of EBV - driving role of LMP1 and LMP2

Increase in Bcl-2

Decrease in checkpoint p16

p27

Increase in cell proliferation and survival - increase in JNK, ERK/MEK, NF-kb, PI3K/ Akt

Increase in Ras, PI3K/ Akt

Decrease in BcR

EBV latency

PTLD - post transplant lymphoproliferative disorder

drug induced immunosuppression

Increases the risk of new infections

Reactivates latent infections - EBV

Causes immune dysregulation

Increase the risk of lymphoma

25-60% patients may die of PTLD

PTLD incidence

Incidence highest in heart-lung, lung or intestinal transplant up to 20%
Liver or heart 1-5%

Less likely in renal, HPSC transplant 1-2%

60% occurs within the first 6 months after transplant

but 10-15% also occur >10years after transplant

Cardinal features of PTLD

Variation of disruption of the lymphoid architecture - exacerbation of a reactive pattern, may not be clonal

Pleomorphic

to DESTRUCTION of the lymph node structure: Monomorphic clonal

Reactive pattern

Follicular hyperplasia

Plasma cell hyperplasia

Destructive

Large B-cell lymphoma

clonal  k or l 

Starry pattern