Lymphoma and Plasma Cell Neoplasms
Other
Other iatrogenic immunodeficiency-associated lymphoproliferative disorders

Reviewer: Dragos Luca, M.D. (see Authors page)

Revised: 8 March 2016, last major update January 2012

Copyright: (c) 2001-2016, PathologyOutlines.com, Inc.

PubMed Search: iatrogenic immunodeficiency associated lymphoproliferative disorders
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 non-immunocompromised patients
  • Terminology
  • Spectrum from polymorphic proliferations resembling polymorphic post-transplantation lymphoproliferative disorders (P-PTLD) to cases that fulfil 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
  • 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 2-20x 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
  • 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
  • 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
  • Micro 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%
  • Micro Images

    Images hosted on PathOut server:

    Case of the Week #381:


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    Images hosted on other servers:

    Diffuse large B cell lymphoma in metrotrexate treated rheumatoid arthritis


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    Nodular sclerosing classic Hodgkin lymphoma in metrotrexate treated dermatomyositis

    Molecular / Cytogenetics Description
  • Similar to corresponding lymphomas in non-immunocompromised patients