Hodgkin's disease and B cell lymphoproliferation in rheumatoid arthritis patients treated with methotrexate: A kinetic study of lymph node changes

Abstract

We describe 2 patients with seropositive rheumatoid arthritis treated with methotrexate (MTX) who developed Hodgkin's disease (HD) and non-Hodgkin's lymphoma. Followup allowed a lymph node biopsy at 4 different time points in 1 patient and at 2 in the other. In the first patient, the steps included a long history of benign follicle hyperplasia, a polymorphic diffuse B cell lymphoproliferation, and finally HD unassociated with Epstein-Barr virus (EBV). In the second patient, a polymorphic diffuse lymphoproliferation was followed by a monomorphic large B cell lymphoproliferation associated with EBV. The cytogenetic analysis showed a monoclonal proliferation associated with the same chromosomal abnormalities found in 1 of the clones observed in the initial biopsy. These 2 cases illustrate the complexity of the role of MTX in the outbreak of such manifestations.

Self-resolution of Epstein-Barr virus–associated B-cell lymphoma in a patient with dermatomyositis following withdrawal of mycophenolate mofetil and methotrexate

“…2,3,5,7,19,20,21,23,24,27,29,35,36,37,40 The use of methotrexate in both rheumatic and nonrheumatic diseases has been reported with the development of lymphoma (Table I). 2,3,7,13,20,21,23,24,25,27,29,[35][36][37][38][39][40][41][42][43][44] The majority of patients, 13, were treated for rheumatoid arthritis followed by DM in 3 cases, and one case each of arthritis-not otherwise specified, psoriasis vulgaris, and systemic lupus erythematosus, respectively. Nine cases of EBV(+) lymphomas were treated with only withdrawal of methotrexate therapy.…”

“…2,3,5,7,13,24,35 There was complete resolution in 8 of these 9 patients. Overall, 9 patients were given chemotherapy, radiation therapy, or a combination of radiation and chemotherapy at the time of lymphoma diagnosis or for progressive or recurrent disease 7,13,20,26,27,[36][37][38][39][40][41][42][43] with 5 of these patients achieving complete resolution.…”

Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France

“…37 Typical HD has, however, also been described in RA patients receiving MTX. [37][38][39][40] It is noteworthy that in 2 cases in the literature the lymphoproliferation, which decreased after MTX withdrawal perhaps only because steroids were increased to control the activity of RA, recurred several months later. 39,40 Among our 3 patients with HD who were treated with MTX withdrawal alone without any chemotherapy for at least 6 months, none of them experienced spontaneous remission.…”

Rheumatoid arthritis and malignancies

“…[50]. В дальнейшем в литературе встречались описания случаев подобных ассоциаций, а также случаев регрессии неходжкинских лимфом после отмены МТ у больных РА [51][52][53].…”