Lymphoma & related disorders
Other immunosuppression related
Other immunodeficiency associated
Author: Dragos C. Luca, M.D.
Topic Completed: 1 January 2012
Minor changes: 29 December 2020
Copyright: 2001-2021, PathologyOutlines.com, Inc.
PubMed Search: iatrogenic immunodeficiency associated lymphoproliferative disorders
Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiology | Clinical features | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Molecular / cytogenetics description | Additional referencesCite this page: Luca DC. Other immunodeficiency associated. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomanonBiatroLPD.html. Accessed March 4th, 2021.
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 #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 #381
CD3
CD20
CD30
CD79a
EBV-EBER
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
