Purpose: We have recently reported EBV+ B-cell lymphoproliferative disorders (LPD) occurring predominantly in elderly patients, which shared features of EBV+ B-cell neoplasms arising in the immunologically deteriorated patients despite no predisposing immunodeficiency and were named as senile or age-related EBV+ B-cell LPDs.To further characterize this disease, age-related EBV+ B-cell LPDs were compared with EBV-negative diffuse large B-cell lymphomas (DLBCL). Experimental Design: Among 1,792 large B-cell LPD cases, 96 EBV+ cases with available clinical data set were enrolled for the present study. For the control group, 107 patients aged over 40 years with EBV-negative DLBCL were selected.We compared clinicopathologic data between two groups and determined prognostic factors by univariate and multivariate analysis. Results: Patients with age-related EBV+ B-cell LPDs showed a higher age distribution and aggressive clinical features or parameters than EBV-negative DLBCLs: 44% with performance status >1, 58% with serum lactate dehydrogenase level higher than normal, 49% with B symptoms, and higher involvement of skin and lung. Overall survival was thus significantly inferior in age-related EBV+ group than in DLBCLs. Univariate and multivariate analyses further identified two factors, B symptoms and age older than 70 years, independently predictive for survival. A prognostic model using these two variables well defined three risk groups: low risk (no adverse factors), intermediate risk (one factor), and high risk (two factors). Conclusions: These findings suggest that age-related EBV+ B-cell LPDs constitute a distinct group, and innovative therapeutic strategies such as EBV-targeted T-cell therapy should be developed for this uncommon disease.

C(+SS) is associated with less advanced, slower growing tumors and better survival compared with C(-SS). In many cases of C(+SS), the survival does not depend on the complete resection of all the superficial spread but on the stage of the main lesion.

Age-related Epstein-Barr virus-associated Bcell lymphoproliferative disorder (aEBVLPD)is a disease group characterized by EBVassociated large B-cell lymphoma in the elderly without predisposing immunodeficiency. In nearly one-third of cases, aEBV-LPD occurs as a polymorphous subtype with reactive cell-rich components, bearing a morphologic similarity to classic Hodgkin lymphoma (cHL). The aim of this study was to clarify clinicopathologic differences between the polymorphic subtype of aEBV-LPD (n ‫؍‬ 34) and EBV ؉ cHL (n ‫؍‬ 108) in patients aged 50 years or older. Results showed that aEBVLPD was more closely associated with aggressive clinical parameters than cHL, with a higher age at onset (71 vs 63 years); lower male predominance (male-female ratio, 1.4 vs 3.3); and a higher rate of involvement of the skin (18% vs 2%), gastrointestinal tract (15% vs 4%), and lung (12% vs 2%). aEBVLPD was histopathologically characterized by a higher ratio of geographic necrosis, greater increase (> 30%) in cytotoxic T cells among background lymphocytes, higher positivity for CD20 and EBNA2, and absence of CD15 expression. As predicted by the clinical profile, aEBV-LPD had a significantly poorer prognosis than EBV ؉ cHL (P < . IntroductionEpstein-Barr virus (EBV), a member of the herpes virus family, infects more than 90% of the worldwide adult population. 1,2 In vitro, EBV randomly infects resting B cells and transforms them into lymphoblastoid cell lines. This property makes it a candidate causative agent for many human cancers, including Burkitt lymphoma, 3,4 Hodgkin lymphoma, 1 immunodeficiency-associated lymphoproliferative disorders (LPDs), 5 and some diffuse large B-cell lymphomas. 6 Although the mechanism of this effect has not been precisely identified, 2 events that cause the lymphoblastoid cell to survive and evolve into a lymphoma are assumed: first, the EBV-infected cell must be unable to exit the cell cycle to become a resting memory B cell; and second, the cytotoxic T-cell response must be impeded so that the lymphoblast is not killed. It is thus widely accepted that T cells play a prominent role in controlling EBV-associated oncogenesis. 1 In support of this, administration of immunosuppressive agents such as tacrolimus or cyclosporin A to prevent the rejection of organ transplants sometimes causes EBV-positive B-cell LPDs. 7,8 On these bases, the tumor microenvironment is thought to play an important role in the pathogenesis and tumor progression of EBV-associated B-cell neoplasms.The World Health Organization (WHO) classification for hematopoietic neoplasm currently categorizes immunodeficiencyassociated LPDs into 4 main groups 9 : (1) LPDs associated with primary immunodeficiency syndromes and other primary immune disorders 10-12 ; (2) lymphomas associated with infection with human immunodeficiency virus (HIV) [13][14][15] ; (3) posttransplantation LPDs (PTLDs) in patients who have received a solid organ or bone marrow allograft [16][17][18][19] ; and (4) methotrexate-associated LPDs, most commonly seen in p...

Epstein-Barr virus (EBV) is

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