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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.
AuthorsEric Y Loo, L Jeffrey Medeiros, Tariq N Aladily, Daniela Hoehn, Rashmi Kanagal-Shamanna, Ken H Young, Pei Lin, Carlos E Bueso-Ramos, John T Manning Jr, Keyur Patel, Vilmos Thomazy, Russell K Brynes, Maitrayee Goswami, Luis E Fayad, Roberto N Miranda
JournalThe American journal of surgical pathology (Am J Surg Pathol) Vol. 37 Issue 8 Pg. 1290-7 (Aug 2013) ISSN: 1532-0979 [Electronic] United States
PMID23774171 (Publication Type: Journal Article)
Chemical References
  • Antigens, CD20
  • Biomarkers, Tumor
  • Epstein-Barr virus encoded RNA 1
  • Immunosuppressive Agents
  • Lewis X Antigen
  • RNA, Viral
  • FUT4 protein, human
  • Fucosyltransferases
Topics
  • Adult
  • Aged
  • Antigens, CD20 (analysis)
  • Autoimmune Diseases (drug therapy, immunology)
  • Biomarkers, Tumor (analysis)
  • Female
  • Fucosyltransferases (analysis)
  • Herpesvirus 4, Human (genetics)
  • Histiocytes (immunology)
  • Hodgkin Disease (immunology, pathology, therapy, virology)
  • Humans
  • Iatrogenic Disease
  • Immunocompromised Host
  • Immunohistochemistry
  • Immunosuppressive Agents (adverse effects)
  • In Situ Hybridization
  • Lewis X Antigen (analysis)
  • Male
  • Middle Aged
  • RNA, Viral (analysis)
  • Reed-Sternberg Cells (immunology, pathology)
  • Remission Induction
  • T-Lymphocytes, Regulatory (immunology)
  • Time Factors
  • Treatment Outcome
  • Tumor Microenvironment

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