Spontaneous regression of breast lymphoproliferative disorders after withdrawal of methotrexate in rheumatoid arthritis patients with Epstein-Barr virus infection: a case report and review of the literature

J Med Case Rep. 2022 Feb 7;16(1):49. doi: 10.1186/s13256-022-03274-1.

Abstract

Background: Lymphoproliferative disorder (LPD) has been shown to occur after treatment with methotrexate (MTX). Currently, MTX-LPD has become widely recognized, but its mechanism and prognostic factors remain unclear.

Case presentation: We report the first case of Epstein-Barr virus (EBV)-associated MTX-LPD of the breast. A 63-year-old Asian woman with long-term rheumatoid arthritis presented to our facility with intermittent fever. A physical examination revealed a 3-cm lump in her left breast. She had been taking MTX for the past 15 years. Laboratory studies revealed slightly elevated levels of EBV-viral capsid antigen antibody immunoglobulin G and EBV nuclear antibody. Contrast-enhanced computer tomography revealed a mass in the left breast, a subcutaneous nodule in the abdomen, a mass in the left lung, and a nodule in the left retroperitoneum. The definitive diagnosis was consistent with MTX-LPD merging into an EBV-positive, diffuse large B-cell lymphoma. Six months following the withdrawal of MTX, the breast mass had markedly shrunk and the patient remained in good health for 1 year with no evidence of relapse of LPD.

Conclusion: MTX-LPD rarely occurs in the breast, and it is difficult to diagnose because there have only been six reported cases of breast MTX-LPD reported in the literature. EBV-positive MTX-LPD tends to regress spontaneously after MTX withdrawal, and our case also had similar results. It is important to make an appropriate diagnosis of MTX-LPD of the breast based on imaging and pathology to determine the appropriate treatment protocol for this rare disorder.

Keywords: Breast lymphoma; Epstein–Barr virus (EBV); Methotrexate-associated lymphoproliferative disorders (MTX-LPD); Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD).

Publication types

  • Case Reports
  • Review

MeSH terms

  • Arthritis, Rheumatoid* / drug therapy
  • Epstein-Barr Virus Infections* / complications
  • Epstein-Barr Virus Infections* / diagnosis
  • Female
  • Herpesvirus 4, Human
  • Humans
  • Lymphoproliferative Disorders* / chemically induced
  • Lymphoproliferative Disorders* / drug therapy
  • Methotrexate / adverse effects
  • Middle Aged
  • Neoplasm Recurrence, Local

Substances

  • Methotrexate