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Methtrexate-associated lymphoproliferative disorders. A clinicopathological study of 13 Japanese cases
Masaru Kojima1, Hideaki Itoh, Kaoru Hirabayashi
1Department of Pathology and Clinical Laboratories, Gunma Cancer Center Hospital, Ohta, Japan. mkojima@gunma-cc.jp
Abstract:
We conducted clinicopathological and immunohistochemical analyses to investigate the prevalence of Epstein-Barr virus (EBV) among 13 cases with methotrexate (MTX)-associated lymphoproliferative disorder (LPD). The subjects of this study were four men and nine women ranging in age from 53 to 78 years (mean: 63 years). All 13 patients had received low dose MTX therapy for 1-13 years before the onset of LPD (mean: 5.8 years). LPDs were found at extranodal sites in six cases, and the disease stage was advanced in seven cases. The present study confirmed certain aspects of a previous observation made in the USA, including the following findings (i) the cases commonly showed diffuse large B-cell lymphomas (n=4) and Hodgkin lymphomas (HL) (n=3), (ii) EBV-encoded small RNA (EBER) + cells were identified in seven cases (60%), which is a much higher percentage than would be expected in lymphomas occurring in a general population, and (iii) three cases of polymorphous small lymphocytic or lymphoplasmacytic infiltrate achieved spontaneous remission of LPDs after MTX withdrawal. Of seven cases of EBER + in our series, three cases were PSLLPI, and two were HL. EBER + tumor cells were detected in only two (30%) of the seven cases with non-Hodgkin lymphomas. The present study suggests that EBV- associated non-Hodgkin lymphomas comprise only a portion of all non-Hodgkin lymphomas among MTX-associated LPDs.
Insights
Epstein-Barr virus (EBV) is prevalent in methotrexate (MTX)-associated lymphoproliferative disorders (LPD), particularly in Hodgkin lymphomas. EBV-associated non-Hodgkin lymphomas represent a subset of MTX-LPDs.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Methotrexate (MTX) is a common immunosuppressant used in treating various autoimmune diseases.
- MTX therapy can be associated with the development of lymphoproliferative disorders (LPDs).
- The role of Epstein-Barr virus (EBV) in MTX-associated LPDs requires further investigation.
Purpose of the Study:
- To investigate the prevalence of Epstein-Barr virus (EBV) in patients with methotrexate (MTX)-associated lymphoproliferative disorder (LPD).
- To characterize the clinicopathological features of MTX-associated LPDs and their association with EBV.
- To determine the types of lymphomas associated with EBV in this patient cohort.
Main Methods:
- Clinicopathological and immunohistochemical analyses were performed on 13 cases of MTX-associated LPD.
- Epstein-Barr virus-encoded small RNA (EBER) expression was assessed using immunohistochemistry.
- Patient data including age, sex, MTX treatment duration, and disease characteristics were reviewed.
Main Results:
- EBV-encoded small RNA (EBER) positive cells were identified in 7 out of 13 cases (60%) of MTX-associated LPD.
- Common lymphoma subtypes included diffuse large B-cell lymphomas (n=4) and Hodgkin lymphomas (HL) (n=3).
- EBV positivity was higher in Hodgkin lymphomas and polymorphous small lymphocytic/lymphoplasmacytic infiltrates compared to non-Hodgkin lymphomas.
Conclusions:
- Epstein-Barr virus (EBV) plays a significant role in a substantial proportion of methotrexate (MTX)-associated lymphoproliferative disorders (LPDs).
- EBV-associated non-Hodgkin lymphomas constitute a specific subset within the broader spectrum of MTX-LPDs.
- Spontaneous remission of LPDs was observed in some cases following MTX withdrawal, particularly in EBV-positive polymorphous small lymphocytic/lymphoplasmacytic infiltrates.