Lymphoma and Other Lymphoproliferative Disorders in IBD: A Review.

Oct 2012

Subramaniam K, D'Rozario J, Pavli P.

Source

Gastroenterology and Hepatology Unit, Canberra Hospital, ACT.

Abstract

The lymphoproliferative disorders (LD) are a heterogeneous group of at least 70 conditions that result from the clonal proliferation of B, T and NK cells. IBD-associated lymphomas are typically B-cell LD, while T-cell or Hodgkin's lymphomas are rare. In IBD patients not on immunosuppression, the risk of LD seems to be similar or slightly higher than the background population risk. Thiopurine therapy is associated with an increased risk: the relative risk is increased 4-6 fold and the absolute risk varies between 1 in 4,000-5,000 for those aged 20-29 to 1 in 300-400 in those over 70. It is difficult to quantify the risk of anti-TNF therapy alone, however it appears to be less than for thiopurines alone. There is particular concern regarding: the development of post-transplant-like LD in those with latent EBV infection exposed to immunosuppressives; the occurrence of hepatosplenic T cell lymphoma in patients treated with combination anti-TNF and thiopurine therapy; and the development of hemophagocytic lymphohistiocytosis in those who acquire a primary EBV or other infection whilst on immunosuppressive medication. There are currently no guidelines for monitoring EBV (or other virus) status in patients on immunosuppression, although it could be used to monitor those who have a prior history of lymphoma and are about to start a thiopurine or anti-TNF agent. In discussing the risks of lymphoproliferative disorders associated with agents used for the treatment of IBD, patients can often be reassured that the benefits of such therapy still outweigh the small, but real, risks.

PubMed

Epstein Barr virus presence in pediatric diffuse large B-cell lymphoma reveals a particular association and latency patterns. Analysis of viral role in tumor microenvironment.

Sept 2012

Cohen M, De Matteo E, Narbaitz M, Carreño FA, Preciado MV, Chabay PA.

Source

Molecular Biology laboratory. Pathology Division. Ricardo Gutiérrez Children's Hospital. Buenos Aires, Argentina. melucohen@ffyb.uba.ar.

Abstract

Non-Hodgkin's lymphoma represents 6-10% of pediatric malignancies, and diffuse large B-cell lymphoma (DLBCL) is one of the 3 major subtypes. The 2008 WHO classification included a new entity, Epstein-Barr virus (EBV)-positive DLBCL of the elderly, affecting patients >50 years. It has been demonstrated that EBV may play a role in tumor microenvironment composition, disturbing anti-tumor immune response and disease progression.

Since most studies were performed in adults, our aim was to assess EBV presence and latency pattern, as well as T-cell microenvironment in a pediatric DLBCL series of Argentina. The study was conducted on formalin-fixed paraffin-embedded biopsies from 25 DLBCL patients. EBERs expression was performed by in situ hybridization, while EBV gene expression was analyzed using real-time PCR. LMP1, LMP2A, CD3, CD4, CD8 and Foxp3 expression were assessed by immunohistochemistry (IHC). Forty percent of cases showed EBV expression, with a significantly higher incidence among patients <10 years (p=0.018), and with immunosuppressed (p=0.023). T-cell subsets were not altered by EBV presence. 

Full EBV latency antigen expression (latency type III) was the most frequently pattern observed, together with BZLF1 lytic gene expression. One patient showed II like pattern (LMP1 without LMP2A expression). Based exclusively on IHC, some patients showed latency II/III (EBERs and LMP1 expression) or I (EBERs only). These findings suggest that EBV association in our series was higher than the previously demonstrated for elderly DLBCL and that EBV latency pattern could be more complex from those previously observed. Therefore, EBV could be an important cofactor in pediatric DLBCL lymphomagenesis.

PubMed