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:
CD3
CD20
CD30
CD79a
EBV-EBER
Diffuse large B cell lymphoma (Figure 1)
Nodular sclerosing
classic Hodgkin
lymphoma (Figure 2) Molecular / cytogenetics description
Similar to corresponding lymphomas in nonimmunocompromised patients
