Methotrexate-related Epstein-Barr virus-associated lymphoproliferative disorder occurring in the gingiva of a patient with rheumatoid arthritis

Abstract

It is well recognized that patients with immunodeficiency have a high risk of development of lymphoproliferative disorders (LPDs), and Epstein-Barr virus (EBV) is associated with the occurrence of LPDs. Methotrexate (MTX) is one of the common cause of iatrogenic-associated LPD, and approximately 40-50% of MTX-related LPD cases occur in extranodal sites. However, the occurrence of MTX-related LPD in the gingiva is extremely rare. Herein, we report the fourth documented case of MTX-related EBV-associated LPD occurring in the gingiva of a patient with rheumatoid arthritis (RA). A 76-year-old Japanese female with a 10-year history of RA, who was treated with MTX and infliximab, presented with a tumorous lesion in the gingiva. Biopsy of the gingiva tumor revealed diffuse proliferation of large-sized lymphoid cells with cleaved nuclei containing conspicuous nucleoli. These lymphoid cells were CD20- and EBER-positive. Therefore, a diagnosis of MTX-related EBV-associated LPD showing features of diffuse large B-cell lymphoma (DLBCL) that occurred in the gingiva was made. Although the occurrence of LPD in the oral region, as seen in the present case, is rare, the prevalence of this disorder may be on the rise due to the increased number of patients undergoing immunosuppression therapy. Moreover, immunosenescence can also be a cause of EBV-associated LPD. Therefore, recognition of the occurrence of this disorder in the oral cavity and consideration of the clinical history can facilitate the correct diagnosis.

Keywords: Epstein-Barr virus; Lymphoproliferative disorder; gingiva; methotrexate.

Figure 1

Histopathological features of the gingiva tumor. A: Diffuse proliferation of lymphoid cells with ulceration, HE, x 40. B: Proliferation of large-sized lymphoid cells with large convoluted nuclei containing conspicuous nucleoli accompanied by infiltration of small lymphocytes and histiocytes, HE, x 400.

Figure 2

Immunohistochemical and in situ hybridization findings of the gingiva tumor. A: CD20 is expressed in the large-sized lymphoid cells, x 400. B: Many EBER-positive cells are detected by in situ hybridization, x 100.

Figure 3

Histopathological and in situ hybridization findings of the gastric ulcer. A few atypical lymphoid cells are observed in the lamina propria (arrows), HE, x 400. A few EBER-positive cells are detected (inset, x 400).