title: Epstein-Barr virus (EBV)-induced B-cell proliferative disorder after chemotherapy in a patient with hemophagocytic lymphohistiocytosis with associated EBV-induced T-cell proliferation.
abstract: We report a case of Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) which developed after chemotherapy for hemophagocytic lymphohistiocytosis (HLH), who had no history of immunodeficiency or familial X-linked LPD. In HLH, the presence of EBV in T-cells was confirmed by a combination of in situ hybridization (ISH) and immunostaining. Southern blot analysis using EBV-TR and immunoglobulin JH probes revealed oligoclonal proliferation of B-cells in each organ involved by abnormal B-lymphoid cells at autopsy. Combined ISH and immunostaining disclosed the presence of EBV in proliferating B-cells. Cytokine analysis during the period of T-cell activation in HLH revealed marked elevation of interferon (IFN) gamma, interleukin (IL)-10 and soluble IL-2 receptor (sIL-2R) and mild to moderate increases of tumor necrosis factor (TNF)-alpha were observed, while IFN gamma, IL-10 and sIL-2R were elevated initially during the HLH phase, which then decreased as LPD developed and B-cell proliferation predominated. Immunosuppressive chemotherapy for HLH may then have allowed latent EBV in B lymphocytes to induce transformation and oligoclonal proliferation of B-cells, finally resulting in LPD. Mechanisms of EBV-induced cell proliferation remain unclear, but alteration of various cytokines may be responsible for it.
authors.affiliation: First Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan. junsuzu@fukuoka-u.ac.jp
authors.forename: J
authors.initials: J
authors.lastname: Suzumiya
authors.forename: K
authors.initials: K
authors.lastname: Ohshima
authors.forename: M
authors.initials: M
authors.lastname: Kanda
authors.forename: M
authors.initials: M
authors.lastname: Kumagawa
authors.forename: M
authors.initials: M
authors.lastname: Nagano
authors.forename: M
authors.initials: M
authors.lastname: Hirata
authors.forename: Y
authors.initials: Y
authors.lastname: Nawa
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000473:pathology* / Q000821:virology; D015139:Blotting, Southern; D001932:Brain Neoplasms / Q000209:etiology / Q000235:genetics / Q000821:virology; D002455:Cell Division; D002472:Cell Transformation, Viral; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D017809:Fatal Outcome; D004854:Herpesvirus 4, Human / Q000302:isolation & purification* / Q000472:pathogenicity; D015616:Histiocytosis, Non-Langerhans-Cell / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D007621:Karyotyping; D008213:Lymphocyte Activation; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology* / Q000235:genetics / Q000821:virology; D008297:Male; D016133:Polymerase Chain Reaction; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000473:pathology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014412:Tumor Virus Infections / Q000150:complications*; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D007371:Interferon-gamma; D003520:Cyclophosphamide; D011239:Prednisolone