Age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorders: special references to lymphomas surrounding this newly recognized clinicopathologic disease

Abstract

Epstein-Barr virus (EBV) is associated with some disease entities of malignant lymphomas, including Burkitt lymphoma, Hodgkin lymphoma, immunodeficiency-associated lymphoproliferative disorders (LPD), and a part of diffuse large B-cell lymphoma. We have recently identified a series of elderly patients with EBV-associated (or EBV(+)) B-cell LPD (B-LPD) showing similarities in many respects to immunodeficiency-associated LPD, although no evidence of underlying immunodeficiency was found. Therefore, the nosological category of senile or age-related EBV(+) B-LPD has been proposed for those patients. A larger series of patients with this disease revealed that the relative ratios of such EBV(+) B-LPD to all diffuse large B-cell lymphoma cases were higher with increasing with age, reaching a peak (20-30%) at > or =90 years of age, with a median of 71 years, providing additional evidence for our assertion that this disease may be related to immunological deterioration as a result of the aging process. This new disease entity is characterized pathologically by centroblasts, immunoblasts, and Hodgkin and Reed-Sternberg-like giant cells with a varying degree of reactive components, often posing therapeutic and diagnostic problems for hematologists and pathologists, respectively. The aim of the present review is to briefly summarize the overall clinicopathological profile of this newly recognized age-related (also called 'senile') EBV(+) B-LPD and EBV(+) Hodgkin lymphoma for a practical diagnostic approach.

Figure 1

Age distribution of patients with Epstein–Barr virus‐associated B‐cell lymphoproliferative disorders (B‐LPD). (a) No. cases and (b) positive percentages for all cases examined.

Figure 2

Age‐related Epstein–Barr virus‐positive B‐cell lymphoproliferative disorder, polymorphous subtype, arising in a 67‐year‐old male. (a) The lesion shows a scattered distribution of Hodgkin and Reed–Sternberg‐like giant cells. (b) These large cells show the expression of CD20 in addition to (c) positive signals for Epstein–Barr virus‐encoded small RNA on in situ hybridization.

Figure 3

Overall survival curve of age‐related Epstein–Barr virus (EBV)⁺ B‐cell lymphoproliferative disorders (B‐LPD) in comparison with EBV⁻ diffuse large B‐cell lymphoma (DLBCL).^{( 7 )} Age‐related EBV⁺ B‐LPD showed significantly worse survival than EBV⁻ DLBCL.

Figure 4

Age distribution of patients with Epstein–Barr virus (EBV)‐associated and non‐associated classical Hodgkin lymphoma (cHL).^{( 15 )} black and yellow bars indicate the number of EBV‐associated and non‐associated cases of cHL, respectively.

Figure 5

Age distribution of patients with Epstein–Barr virus (EBV)⁺ classical Hodgkin lymphoma (cHL),^{( 15 )} and EBV⁺ diffuse large B‐cell lymphoma (DLBCL),^{( 7 )} lacking evidence of underlying immunodeficiency. (a) These diseases have different patterns, because cHL is characterized by a relatively younger onset. However, in the combined series, these two diseases show the highest incidence peak at 70–79 years of age (b). The relative ratio of EBV⁺ DLBCL to EBV⁺ cHL rose in parallel with the older patient populations (≥50 years).