EBV-associated DLBCL

Definition: EBV-positive DLBCL of the elderly is a diagnosis that was recently added as a new category of lymphoma in the 2008 WHO Classification Tumours of Haematopoietic and Lymphoid Tissues, as a provisional clinicopathological entity.

Given the poor prognosis (mean survival: 2 years), the diagnosis of EBV-positive DLBCL must be clearly determined, and a diagnosis of diffuse large B cell lymphoma, not otherwise (DLBCL, NOS) specified, should be avoided.

EBV-positive DLBCL has been reported in patients less than 50 years old without immunosuppression. Current definitions of this entity may need revision to include these younger patients.

It is a clonal B cell lymphoma that invariably shows Epstein Barr virus infection and by definition must occur in patients older than 50 years who do not have known immunodeficiency or prior lymphoma. These patients may not be immunodeficient due to transplantation, autoimmunity or from medication.

Approximately 70% of these tumors are found in extranodal locations, including the head and neck.

EBV-positive DLBCL is thought to arise from declining immunity related to senescence; however, a clear etiology is not yet known. Similar to ENKTL, EBV-positive DLBCL of the elderly more frequently occurs in the Asian population.

Microscopy

This tumor consists of medium to large transformed B cells in a background of small reactive cells including lymphocytes and histiocytes.

Geographic necrosis is frequently seen, and the tumor cells may resemble centroblasts, immunoblasts or Hodgkin Reed Sternberg-like cells with more prominent nucleoli and binucleation.

Immunohistochemistry

The malignant B cells are immunoreactive for B cells markers such as CD20, OCT2, CD79a, BoB.1 and PAX5.

Lesional cells are EBER positive; EBV-related immunohistochemical markers such as LMP1 and EBNA2 may be positive.

At least one of the following markers EBER, LMP1 or EBNA2 must be positive to establish the diagnosis; if EBV is absent then the diagnosis is excluded.

In situ hybridization studies for EBER is the most sensitive method of detecting EBV infection. EBER typically highlights all of the lymphoma cells.

CD30 appears to be often immunoreactive; and CD10 appears to be less often positive as compared to EBV-negative diffuse large B cell lymphoma.

CD15 is characteristically negative, a finding that assists in separating the tumor from classical Hodgkin lymphoma.

It is also recognized that these cases are typically of non-germinal center phenotype characterized by BCL6(-), CD10(-) and MUM1 (+) using the Hans algorithm.

Molecular biology

Molecular studies are typically utilized to detect Ig heavy chain gene rearrangement, which is found in the majority of cases.

By array based comparative genomic profiling, there are many known genetic abnormalities in EBV-positive DLBCL, many of which overlap with plasmablastic lymphoma and post- transplant lymphoproliferative disorder, implying that there may be overlap between these three entities.

Activation of JAK/STAT and NK-kB may also play a role in this tumor since there are known mutations of CARD11 and CD79B.

Prognosis

The prognosis of EBV-positive DLBCL is typically worse than EBV-negative DLBCL.

Older age, lymphadenopathy and B symptoms are considered poor prognostic indicators.

Mean survival of these patients is approximately 2 years, and the prognosis remains poor even with rituximab treatment plus chemotherapy (CHOP).

Localization

 head adn neck

• Simlar to Extranodal NK/T-cell lymphoma, nasal type (ENKTL), Epstein-Barr virus-associated diffuse large B cell lymphoma of the elderly may also present as an EBV-positive tumor in the head and neck.
• However, EBV-positive DLBCL is easily distinguishable from ENKTL because it consists of B cells and will express B cell markers.

References

 http://www.semdiagpath.com/article/S0740-2570(14)00108-7/fulltext#s0035