Methotrexate-associated lymphoproliferative disorder demonstrating composite lymphoma of EBV-negative diffuse large B-cell lymphoma and EBV-positive mucocutaneous ulcer

Abstract

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (Oiia-LPD) has been defined as lymphoproliferative disorders or lymphomas developing in patients receiving immunosuppressive drugs for autoimmune diseases or conditions other than in the post-transplant setting. 1 In particular, many rheumatoid arthritis (RA) patients are treated using methotrexate (MTX). The pathological features of MTX-LPD vary. Histology of diffuse large B-cell lymphoma (DLBCL) is predominant, followed by that of classic Hodgkin lymphoma (CHL). 1,2 Among the different types of MTX-LPD, composite lymphoma of MTX-LPD has rarely been reported. 3-7 All cases except one were a composite of B-cell lymphoma and T-cell lymphoma. 3-6 The other was a composite of DLBCL and follicular lymphoma (FL). 7 There has been no report of a case with Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (EBVMCU). EBVMCU were recently reported to develop as MTX-LPD. EBVMCU are characterized by the proliferation of EBV-positive B-cells that exhibit almost the same histology as lymphoma and spontaneously regress. 8 Although MTX withdrawal is the first choice for patients with MTX-LPD leading to tumor regression, the rate of complete remission (CR) is not high. 1,9 Chemotherapy is required for these patients, but there is no standard regimen. 10 The choice of regimen in each case is usually based on the pathological diagnosis such as DLBCL and CHL. 9 Pathological diagnosis of MTX-LPD is important, but the relationship between pathological findings and clinical courses of MTX-LPD is unclear. We report a case of composite lymphoma in a patient with MTX-LPD. Two biopsies from different sites demonstrated DLBCL with EBV-negative and EBV-positive MCU. Multiple biopsy may be important for MTX-LPD, and we discuss chemotherapy in regards to coincidental pathological features.

Epstein–Barr Virus-Positive Mucocutaneous Ulcer: A Unique and Curious Disease Entity

“…In 186 EBVMCU cases [ 5 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ], during the follow-up periods (1–180 months), spontaneous improvement of the ulcers was noted in eight patients, and 126 patients had either complete or partial remission after discontinuation or dose reduction of immunosuppressants, chemotherapy, or radiotherapy. While eight patients experienced recurrence [ 15 , …”

Clinicopathological evaluation of methotrexate-associated lymphoproliferative disorders with special focus on Epstein-Barr virus-positive mucocutaneous lesions

“…We reported one case of composite lymphoma associated with MTX-LPD that included both EBVMCU in the pharynx and EBV-negative DLBCL with systemic lymphadenopathy ( Table 2B , Case 6). 27 The pharyngeal lesion disappeared after the discontinuation of MTX, although systemic lymphadenopathy remained. Identification of the site of proliferation of EBV-positive large B-cells in the setting of MTX-LPD is another important feature.…”

Case report: Management of Epstein–Barr virus positive and methotrexate‐associated B‐cell lymphoma

“…4 Consequently, chemotherapy was advocated in cases in which the exclusive reliance on MTX discontinuation for achieving regression was deemed impractical. 16 Within the spectrum of available regimens, those incorporating rituximab have been endorsed specifically for cases manifesting lymphoma recurrence or progression with the alternative benefit of covering incidental lymphoma. 5,16 Shimada,et al conducted a retrospective study involving Japanese patients and found that rituximab significantly extended both PFS and OS in patients with RA and OIIA LPD compared with those on non-rituximab chemotherapy regimens.…”