Methotrexate-Related Lymphoproliferative Disorder in Patients With Osteonecrosis of the Jaw: A 3-Case Report and Literature Review

J Oral Maxillofac Surg. 2018 Jan;76(1):97-111. doi: 10.1016/j.joms.2017.05.027. Epub 2017 Jun 1.

Abstract

Patients with immunodeficiency or immunosuppression are at risk of developing a lymphoproliferative disorder (LPD). Methotrexate (MTX) is an iatrogenic cause of LPD, which in up to 50% cases occurs in extranodal sites. The occurrence of MTX-related LPD with osteonecrosis of the jaw (ONJ) has rarely been reported. Moreover, there are no clear diagnostic criteria and treatment strategies for management of these lesions. In the present cases, discontinuing MTX and debridement of the necrotic bone were effective. This report describes 3 cases of MTX-related LPD in patients with longstanding rheumatoid arthritis (RA) who presented with ONJ. The first patient was a 74-year-old man with RA who had received treatment with MTX for 7 years before presenting with ONJ and submental lymphadenopathy. The second patient was a 79-year-old woman who had been treated for 21 years with MTX and who presented with ONJ. The third patient was a 67-year-old man who had been treated with MTX for more than 15 years. In all 3 cases, biopsy, histology, and immunohistochemistry using a panel of lymphoid markers (Epstein-Barr virus [EBV], CD79a, CD20, PAX-5, CD3, and CD30) resulted in the diagnosis of EBV-driven T-cell, B-cell, and Hodgkin-like LPD. All 3 patients recovered after cessation of MTX and surgical debridement. Biopsy examination, diagnostic immunohistochemistry using lymphoid immune markers, and imaging studies using computed tomography, magnetic resonance imaging, and positron-emission tomographic computed tomography were useful for the correct diagnosis of this condition.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / drug therapy
  • Biopsy
  • Debridement
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphoproliferative Disorders / chemically induced*
  • Lymphoproliferative Disorders / diagnostic imaging
  • Lymphoproliferative Disorders / surgery
  • Male
  • Mandibular Diseases / chemically induced*
  • Mandibular Diseases / diagnostic imaging
  • Mandibular Diseases / surgery
  • Maxillary Diseases / chemically induced*
  • Maxillary Diseases / diagnostic imaging
  • Maxillary Diseases / surgery
  • Methotrexate / adverse effects*
  • Osteonecrosis / chemically induced*
  • Osteonecrosis / diagnostic imaging
  • Osteonecrosis / surgery
  • Risk Factors

Substances

  • Methotrexate