PD‐L1 expression is associated with the spontaneous regression of patients with methotrexate‐associated lymphoproliferative disorders

Abstract Background Most patients with methotrexate‐associated lymphoproliferative disorder (MTX‐LPD) show diffuse large B‐cell lymphoma (DLBCL) or classic Hodgkin lymphoma (CHL) types. Patients with MTX‐LPD often have spontaneous remission after MTX discontinuation, but chemotherapeutic intervention is frequently required in patients with CHL‐type MTX‐LPD. In this study, we examined whether programmed cell death‐ligand 1 (PD‐L1) expression levels were associated with the prognosis of MTX‐LPD after MTX discontinuation. Methods A total of 72 Japanese patients diagnosed with MTX‐LPD were clinicopathologically analyzed, and immunohistochemical staining of PD‐L1 was performed in 20 DLBCL‐type and 24 CHL‐type MTX‐LPD cases to compare with the clinical course. Results PD‐L1 was expressed in 5.0% (1/20) of patients with DLBCL‐type MTX‐LPD, whereas it was expressed in 66.7% (16/24) of the patients with CHL‐type MTX‐LPD in more than 51% of tumor cells. Most CHL‐type MTX‐LPD patients with high PD‐L1 expression required chemotherapy owing to exacerbations or relapses after MTX discontinuation. However, no significant differences in clinicopathologic findings at diagnosis were observed between PD‐L1 high‐ and low‐expression CHL‐type MTX‐LPD. Conclusion PD‐L1 expression was significantly higher in patients with CHL‐type than DLBCL‐type MTX‐LPD, suggesting the need for chemotherapy in addition to MTX discontinuation in CHL‐type MTX‐LPD patients to achieve complete remission. No association was observed between PD‐L1 expression levels and clinical findings at diagnosis, suggesting that PD‐L1 expression in tumor cells influences the pathogenesis of CHL‐type MTX‐LPD after MTX discontinuation.