title: Classical Hodgkin lymphoma arising in the setting of iatrogenic immunodeficiency: a clinicopathologic study of 10 cases.
abstract: Iatrogenic immunodeficiency-associated lymphoproliferative disorders are rare. A small subset of these lesions resembles classical Hodgkin lymphoma (CHL), but there are few data in the literature about these lesions. We describe 10 patients with autoimmune diseases treated with immunomodulator therapeutic agents who developed CHL. The autoimmune diseases included rheumatoid arthritis (n=5), systemic lupus erythematosus (n=2), dermatomyositis (n=1), autoimmune hepatitis (n=1), and Crohn disease (n=1), and the immunomodulatory therapies were methotrexate, azathioprine, tumor necrosis factor-α inhibitors, and thalidomide alone or in various combinations. The study group included 9 women and 1 man with a median age of 50 years (range, 25 to 77 y). The histologic features supported CHL in all cases with Reed-Sternberg (RS) and Hodgkin (H) cells in an inflammatory cell background, although the neoplasm could only be subclassified in 3 patients: 2 nodular sclerosis and 1 mixed cellularity. Immunohistochemical analysis supported the diagnosis of CHL. In all cases the RS-H cells were CD30. Nine of 10 cases were CD15, whereas CD20 was expressed variably in 4/10 cases. CD45/LCA was negative in 8 cases assessed. In situ hybridization for Epstein-Barr virus-encoded RNA was positive in the RS-H cells in 8/10 cases. The microenvironment of these lesions depicted a predominance of T-regulatory cells and M2 histiocytes. Clinical follow-up data were available for 7 patients, with a median posttreatment period of 27 months (range, 12 mo to 7 y). In all 7 patients immunomodulatory drug therapy was discontinued, and chemotherapy for CHL was administered; 2 patients also received local radiation. All 7 patients achieved complete remission and are alive. We conclude that iatrogenic immunodeficiency-associated CHL is highly associated with Epstein-Barr virus infection, and patients usually have a good outcome after discontinuation of immunomodulatory agents and chemotherapy for CHL.
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Loo
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Tariq N
authors.initials: TN
authors.lastname: Aladily
authors.forename: Daniela
authors.initials: D
authors.lastname: Hoehn
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kanagal-Shamanna
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
authors.forename: John T
authors.initials: JT
authors.lastname: Manning
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Vilmos
authors.initials: V
authors.lastname: Thomazy
authors.forename: Russell K
authors.initials: RK
authors.lastname: Brynes
authors.forename: Maitrayee
authors.initials: M
authors.lastname: Goswami
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fayad
authors.forename: Roberto N
authors.initials: RN
authors.lastname: Miranda
mesh_terms: D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000032:analysis; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D005647:Fucosyltransferases / Q000032:analysis; D004854:Herpesvirus 4, Human / Q000235:genetics; D006644:Histiocytes / Q000276:immunology; D006689:Hodgkin Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy / Q000821:virology; D006801:Humans; D007049:Iatrogenic Disease; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D017403:In Situ Hybridization; D016256:Lewis X Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000473:pathology; D012074:Remission Induction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D018951:Antigens, CD20; D014408:Biomarkers, Tumor; C099537:Epstein-Barr virus encoded RNA 1; D007166:Immunosuppressive Agents; D016256:Lewis X Antigen; D012367:RNA, Viral; C066693:FUT4 protein, human; D005647:Fucosyltransferases