Lymphoma & related disorders
Other immunosuppression related
Other immunodeficiency associated

Topic Completed: 1 January 2012

Minor changes: 5 July 2020

Copyright: 2001-2020,, Inc.

PubMed Search: iatrogenic immunodeficiency associated lymphoproliferative disorders

Dragos C. Luca, M.D.
Page views in 2019: 274
Page views in 2020 to date: 172
Cite this page: Luca D. Other immunodeficiency associated. website. Accessed August 6th, 2020.
Definition / general
  • Lymphoid proliferations or lymphomas that arise in patients treated with immunosuppressive drugs for autoimmune diseases or conditions other than in the allograft / autograft transplant setting (WHO, 2008)
  • Immunophenotype: Similar to corresponding lymphomas in nonimmunocompromised patients
  • Terminology
  • Spectrum from polymorphic proliferations resembling polymorphic posttransplantation lymphoproliferative disorders (P-PTLD) to cases that fulfill the criteria for diffuse large B cell lymphoma, other B cell lymphomas, peripheral T/NK cell lymphomas or classical Hodgkin lymphoma
  • Epidemiology
  • Frequency not well known, difficult to differentiate if due to iatrogenic immunosuppression, underlying disorder or chance
  • Rate probably is based on presence of underlying disease (rheumatoid arthritis, inflammatory bowel disease, psoriasis and psoriatic arthritis) and particular drug taken
  • First drug reported in this context is methotrexate, predominantly in the setting of rheumatoid arthritis
  • Striking association between hepatosplenic T cell lymphoma and young patients with Crohn's disease treated with infliximab plus azathioprine or 6-mercaptopurine
  • Sites
  • Patients treated with methotrexate: 40 - 50% extranodal (GI, skin, liver, spleen, lung, kidney, thyroid, bone marrow, soft tissue)
  • Hepatosplenic T cell lymphoma patients with Crohn's disease patients treated with infliximab: usually spleen, liver, bone marrow
  • Etiology
  • EBV infection, although rate varies from 40% in rheumatoid arthritis cases treated with methotrexate, 80% in Hodgkin lymphoma, 25% in diffuse large B cell lymphoma, 0% in hepatosplenic T cell lymphoma
  • Other important factors are chronic inflammation, chronic antigen stimulation, genetic background
  • Patients with rheumatoid arthritis have 2 - 20× risk of lymphoma even in the absence of methotrexate
  • Hepatosplenic T cell lymphoma not common in older patients receiving infliximab for inflammatory bowel disease or rheumatoid arthritis
  • Clinical features
  • Similar to immunocompetent patients with the same type of lymphoma
  • Case reports
  • 57 year old woman with rheumatoid arthritis and rapidly growing lesions on face and forehead (Case of the Week #381)
  • Treatment
  • Regression after drug withdrawal occurs in a significant proportion of patients with methotrexate associated lymphoproliferate disorders (majority in EBV+ cases)
  • Regression rates: diffuse large B cell lymphoma – up to 40%, classical Hodgkin lymphoma – up to 30%; most require chemotherapy with an overall survival for diffuse large B cell lymphoma of 50%; following initial regression after drug discontinuation, some patients have recurrences and require chemotherapy
  • Regression is rare for disease due to TNFα blockers
  • Hepatosplenic lymphoma due to infliximab is usually fatal, similar to regular HSTL
  • Microscopic (histologic) description
  • Different distribution of histologic types when compared to other immunodeficiency settings
  • Probable increase in Hodgkin lymphoma and Hodgkin lymphoma-like lymphoid proliferations
  • For patients treated with methotrexate: diffuse large B cell lymphoma (35 - 60%), classical Hodgkin lymphoma (12 - 25%, usually mixed cellularity), follicular lymphoma (5 - 10%), also Burkitt lymphoma, MALT lymphoma and peripheral T cell lymphoma; P-PTLD or P-PTLD-like infiltrates in ~15%
  • Microscopic (histologic) images

    Case of the Week #381:






    Images hosted on other servers:

    Diffuse large B cell lymphoma (Figure 1)

    Nodular sclerosing
    classic Hodgkin
    lymphoma (Figure 2)
    Molecular / cytogenetics description
  • Similar to corresponding lymphomas in nonimmunocompromised patients
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