The aggressive clinical courses of Hodgkin lymphoma primarily diagnosed as methotrexate-induced non-specific lymphoproliferative disorder in patients with rheumatoid arthritis

Abstract

Recently, attention has been focused on methotrexate-induced lymphoproliferative disease (MTX-LPD), and atypical phenotypes are occasionally documented. We encountered two patients with rheumatoid arthritis (RA) who were diagnosed with non-specific LPD (LPD-nos). Biopsy samples were not obtained during the initial examination when the LPD development was discovered, and the patients achieved a complete response after MTX cessation (case 1) or steroid pulse therapy (case 2). However, the tumors flared up 1.5 years later, and LPD-nos was determined following biopsies of the lymph node (LN, case 1) and liver (case 2). Prednisolone was subsequently administered instead of chemotherapy; however, multiple masses, including in the spine (case 1), and severe icterus with liver dysfunction (case 2) were exacerbated within a few months. Although the re-biopsy of LN proved the presence of HL and radiation followed by aggressive chemotherapy rescued the patient (case 1), the superficially accessible biopsy site was not found, and autopsy finally revealed HL (case 2). In both cases, the underlying pathogenesis along with the B symptoms and laboratory abnormalities suggested MTX-LPD, HL in particular. Therefore, even if the pathological diagnosis does not confirm the specific LPD subtype, the administration of aggressive chemotherapy should be considered if the LPD activity flares severely. 〔J Clin Exp Hematop 56(3): 165-169, 2017〕

Methotrexate-Associated Lymphoproliferative Disease of the Thoracic Spine Misdiagnosed as Metastatic Spinal Tumor: A Case Report

“…The musculoskeletal system can be affected by MTX-LPD, with bone marrow infiltration accounting for around 3% of all known MTX-LPD cases [8]. It is extremely uncommon for the bone marrow to invade the spinal column and to our knowledge, there have only been three reported cases of MTX-LPD of the spine [9][10][11][12]. Kikuchi et al reported a rare case of MTX-LPD originating from the lumbar spine for the first time [9].…”

Methotrexate-induced iatrogenic immunodeficiency-associated lymphoproliferative disorder causing hypercalcaemia

“…This patient appears to be in partial remission since she has decreased lymphadenopathy on physical exam, but continued disease involvement seen on imaging. Frequent follow-up is also still warranted as there have been instances of Hodgkin lymphoma from MTX use necessitating aggressive and prompt treatment 13…”

Other Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder, Hodgkin Type, following Epstein-Barr Viral Hepatitis in a Patient with Rheumatoid Arthritis

“…In addition to the possible sampling error, the clinical course of the temporary improvement after the discontinuation of MTX and IFX fits the response to therapy for OIIA-LPD Hodgkin lymphoma. Two cases of Hodgkin lymphoma have been reported in RA patients with antecedent symptoms of suspected MTX-LPD ( 4 ). In this report, the antecedent symptoms improved temporarily with the discontinuation of MTX or steroid pulse therapy but were exacerbated after 1.5 years with aggressive manifestations.…”