Proposal of Progressive Adult Onset EBV-Associated Lymphoproliferative Disorder (PAEBV) as a Rapid-Onset Neoplastic Disease.

Epstein-Barr virus (EBV) is currently recognized as a pathogen of several known human diseases ranging from transient infection, chronic lymphoproliferative disorder (LPD) to EBV-positive malignant lymphomas. Chronic active EBV infection (CAEBV) is typically an indolent but long-lasting EBV-LPD of childhood. Another well documented EBV-associated LPD is the post-transplant EBV-LPD, which also occurs in adults. Fulminant proliferation of EBV after primary infection or in the setting of CAEBV is an aggressive type of disease, which has recently been included in the 4th version of WHO classification as “systemic EBV-positive T-cell LPD of childhood”. Here, we present a previously unrecognized type of EBV-associated LPD mainly developed in adults who experienced progressive clinical course.

A total of 13 adult patients with progressive EBV-LPD was identified from patient files of collaborative institutions. The patient clinical records and data were investigated retrospectively.

There were six males and seven females with an age ranging from 16 to 85 years (median: 27 years). All patients were previously healthy without history of opportunistic infections or administration of immunosuppressants. Patients presented with persistent fever, hepatosplenomegaly and cytopenia, and all showed increasing number of EBV-DNA copies in peripheral blood. Proliferation of T- or NK-cells was recognized. Four patients showed elevated VCA-IgM antibody, and fell in the category of fulminant EBV-positive T-cell LPD after primary EBV infection. However, the other nine showed EBV-antibodies of previous infection. The bone marrow, liver, and lymph nodes were common sites of involvement. Morphological atypia of lymphocytes were faint in peripheral blood or biopsied specimens. Therefore, pathological diagnosis of malignant condition was difficult at the initial presentation. Because of the deteriorating clinical conditions, chemotherapy was administered to 12 patients, but the disease was resistant in 10 patients. Four patients underwent allogeneic hematopoietic stem cell transplantation. In total, 3 patients are alive and 10 patients were dead. The causes of death were primary disease in 5 patients, bleeding in 2, infection in 2, but unknown in one. All but one patient without allogeneic transplantation died within a year. The median survival time was eight months.

In contrast to CAEBV in childhood, these 13 adult patients pursued obviously different, more aggressive clinical courses. However, early diagnosis had been difficult because of the little morphological abnormalities and disease recognition. Prompt administration of cytotoxic chemotherapy and/or stem cell transplantation is possibly needed to conquer this aggressive disease. Therefore, for this purpose, we here propose a novel nomenclature of progressive adult-onset EBV-LPD (PAEBV). PAEBV is (1) the disease with increasing number of EBV-DNA in T or NK cells, (2) the malignant disease without or mild atypia in its early stage, and (3) associated with a poor prognosis. For adolescence or young adults, both classical CAEBV and PAEBV can be recognized. Further investigations for differential diagnosis are required, as well as those for appropriate therapeutic approaches against this rare and intractable disease.

No relevant conflicts of interest to declare.