Epstein--Barr virus-associated B-cell lymphoma in the setting of iatrogenic immune dysregulation presenting initially in the skin.
BACKGROUND
Epstein-Barr virus (EBV) has been implicated in B-cell lymphoma associated with iatrogenic immune dysregulation, primarily in the context of extracutaneous lymphoma.


METHODS
We describe six patients, five transplant recipients receiving cyclosporine and one patient with rheumatoid arthritis receiving methotrexate, who developed cutaneous presentations of EBV-associated B-cell lymphoma. Human herpesvirus 8 (HHV8) and EBV thymidine kinase (vTK) expression were also explored.


RESULTS
The cases comprised plasmablastic lymphoma (one case), plasmacytic marginal zone lymphoma (two cases), and diffuse large B-cell lymphoma (three cases). There was a monoclonal gammopathy in one and concurrent extracutaneous disease in two of the six patients. EBV-associated latent small nuclear RNA was detected in all cases with coexpression of HHV8 in one of the five cases and of vTK in three of the six cases. Three patients responded to a reduction in the immunosuppressive regimen and antiviral therapy. Recurrent disease developed in two, with one patient succumbing to multiorgan dissemination.


CONCLUSIONS
EBV-associated cutaneous B-cell lymphoma is characterized by a long interval between the initiation of immunosuppression and the development of lymphoma. Although previous reports have reported an indolent clinical course, an aggressive clinical course may occur. HHV8 and lytic phase EBV antigens are detected in some cases, possibly suggesting a pathogenetic role.
Verma
Shannon
S
School of Medicine and Public Health, The Ohio State University, Columbus, OH, USA.
Frambach
Gwyn E
GE
Seilstad
Kay H
KH
Nuovo
Gerard
G
Porcu
Pierluigi
P
Magro
Cynthia M
CM
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D003937:Diagnosis, Differential; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D005260:Female; D004854:Herpesvirus 4, Human / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D016867:Immunocompromised Host; D017403:In Situ Hybridization; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000139:chemically induced / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000150:complications* / Q000276:immunology / Q000473:pathology; D013937:Thymidine Kinase / Q000378:metabolism
C099537:Epstein-Barr virus encoded RNA 1; D012333:RNA, Messenger; D012367:RNA, Viral; D013937:Thymidine Kinase