title: Epstein-Barr virus-negative, CD5-positive diffuse large B-cell lymphoma developing after treatment with oral tacrolimus for mixed connective tissue disease : a case report and review of the literature.
abstract: A 69-year-old woman, who had been diagnosed as having Sjögren's syndrome at 37 years old and mixed connective tissue disease at 42 years old, was under treatment with oral prednisolone. In 2009, she was diagnosed as having active systemic lupus erythematosus, and started on treatment with tacrolimus at 3 mg/day. In 2010, para-aortic lymphadenopathy and superficial multiple lymphadenopathy were detected. Tacrolimus was discontinued. Axillary lymph node biopsy revealed Epstein-Barr (EB) virus-negative CD5-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified into clinical stage IIIA and as being at high risk according to the international prognostic index. After the discontinuation of tacrolimus, the lymph nodes reduced temporarily in size. In January 2011, the lymphadenopathy increased again, and the patient received a total of 8 courses of therapy with rituximab, pirarubicin, vincristine, cyclophosphamide and prednisolone, followed by intrathecal injection to prevent central nervous system infiltration, which was followed by complete remission. In February 2012, fluorodeoxyglucose positron emission tomography showed relapse in multiple lymph nodes and central nervous system infiltration. The patient was considered to have iatrogenic lymphoproliferative disorder classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" by the WHO, and this is the first reported case of CD5-positive DLBCL and central nervous system infiltration following administration of the drug. The patient was considered to have a poor prognosis as EB virus was negative, discontinuation of tacrolimus was ineffective and there was evidence of central nervous system infiltration.
authors.affiliation: Division of Hematology, Juntendo University Urayasu Hospital, Chiba, Japan. yasu_sek@juntendo-urayasu.jp
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Sekiguchi
authors.forename: Asami
authors.initials: A
authors.lastname: Shimada
authors.forename: Hidenori
authors.initials: H
authors.lastname: Imai
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Wakabayashi
authors.forename: Keiji
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakamura
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sawada
authors.forename: Norio
authors.initials: N
authors.lastname: Komatsu
authors.forename: Masaaki
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018956:CD5 Antigens / Q000235:genetics / Q000276:immunology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007049:Iatrogenic Disease; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D008947:Mixed Connective Tissue Disease / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D011239:Prednisolone / Q000008:administration & dosage; D000069283:Rituximab; D012859:Sjogren's Syndrome / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D016559:Tacrolimus / Q000009:adverse effects*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018956:CD5 Antigens; D007166:Immunosuppressive Agents; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; C027260:pirarubicin; D016559:Tacrolimus