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
Ogawa, A., Nakagawa, T., Kumaki, Y., Hosoya, T., Oda, G., Mori, M., Fujioka, T., Kubota, K., Onishi, I., & Uetake, H. (2022). 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. Journal of medical case reports, 16(1), 49. https://doi.org/10.1186/s13256-022-03274-1
View Original Source →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.
Case Details
Disease Location
Breast with lung and retroperitoneum metastases
Personal Characteristics
63-year-old asian, diabetes, atypical mycobacteriosis, and hepatitis b, ra for 37 years and had been taking mtx for more than 15 years. (14 mg/week of mtx, 5 mg/day of prednisolone, and 1 mg/day of tacrolimus)
Clinical Characteristics
Presented with intermittent fever of approximately 38.0 °c, which lasted for 2 weeks and did respond to antipyretics. Physical examination showed a 3-cm palpable mass in the left breast. Laboratory studies showed slightly elevated levels of c-reactive protein and soluble interleukin-2 receptor (sil-2r). Ebv-viral capsid antigen antibody immunoglobulin g and ebv nuclear antibody (ebna) were also increased. CT 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. It was suspected that the tumors were related to the use of methotrexate. Thus, mtx was discontinued immediately. One week after mtx withdrawal, craniocaudal and mediolateral oblique mammography showed a high-density mass with undefined margins in the internal lower left breast quadrant. Us) showed a 4.5 cm heterogeneous hyperechoic mass in the internal region of the left breast, which had a low echo area spread like a cord, and blood flow was partially observed along the low echo area. Ultrasound-guided core needle biopsy was performed on the left breast mass. Necrotic tissue and proliferation of atypical lymphocytes with enlarged nuclei around the blood vessel. On immunohistochemical staining, lymphoid cells were positive for CD20, cd79a, and bcl- 2. Ebv-encoded rna1 (eber1), latent membrane protein 1 (lmp1), and ebv-nuclear antigen 2 (ebna2) were positive. The tumors began to shrink after mtx was discontinued the definitive diagnosis was consistent with mtx-lpd merging into an ebv-positive, diffuse large b-cell lymphoma (dlbcl). To treat the patient’s ra, iguratimod, salazosulfapyridine, and bucillamine were prescribed instead of mtx, and they provided adequate ra control
Remission Characteristics
One month following withdrawal of mtx, the breast mass had become smaller, about 2-cm in diameter on us. Six months later, the mass had markedly shrunk like a scar.
Treatment & Mechanisms
Proposed Remission Mechanisms
Ebv-positive mtx-lpd tends to regress spontaneously after withdrawal of mtx
Clinical Treatment
Methotrexate withdrawal
Non-Clinical Treatment
None reported