Clinical and histopathological significance of PD-1 expression in cutaneous lesions of adult T-cell leukemia-lymphoma.

BACKGROUND: Adult T-cell leukemia-lymphoma (ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection and is known to exhibit cutaneous involvement in 50% or more patients. Few studies have evaluated the clinicopathological significance of programmed death-1 (PD-1) expression in the cutaneous lesions of ATL.

METHODS: Skin biopsy specimens from 29 ATL patients with cutaneous lesions were evaluated regarding the clinicopathological feature, survival outcome, and PD-1 expression level on infilitrated CD3+CD4 + CD25+ cells. The optimal cut-off point of PD-1 expression for clinicopathological feature and outcome was determined as the value of the maximum Youden index by receiver operating characteristic (ROC) analysis.

RESULTS: PD-1 was expressed broadly from zero to 90% on the skin biopsy specimens of the 29 patints, with the median value of 50%. The PD-1-expression level was significantly higher in the poorer-prognosis eruption group (nodulotumoral, erythrodermic and purpuric types) (P = 0.003), in the poorer histopathological infiltration patterns (diffuse and nodular) (P = 0.007), and in the poorer infiltrating cell-size group (large-sized cells) (P = 0.017) than in the corresponding group. ROC curve analyses showed that the optimal cut-off value for PD-1-expression level to predict the poorer-prognosis eruption, the poorer- histopathological infiltration pattern, the poorer infiltration cell size, and the poorer outcome (death) was 60%, 50%, 50%, and 80%, respectively. Patients with high PD-1 expression had a shorter median survival time than those with low PD-1 expression (18.2 months vs. 26.0 months), but the difference was not statistically significant.

CONCLUSIONS: ATL patients with cutaneous lesions in which PD-1 were highly expressed have more advanced dermatological and histopathological patterns and possibly worse survival than those with low PD-1 expression on cutaneous lesions. Further large-scale studies are warranted to verify these findings.