Supplementary Material for: Pityriasis Lichenoides et Varioliformis Acuta Developing during Pembrolizumab Treatment for Bladder Cancer

Introduction
Anti-PD-1 immunotherapies enhance T-cell responses against tumor cells by blocking the interaction between PD-1 and its ligand, PD-L1. While these therapies offer significant benefits in treating various malignancies, they can also lead to several immune-related adverse events (irAEs), most notably manifesting in the skin. Lichenoid reactions, eczema, and vitiligo are the three most prevalent forms of cutaneous irAE.

Case presentation
Here, we report a rare case of a pityriasis lichenoides et varioliformis acuta (PLEVA) that developed during pembrolizumab treatment for invasive bladder cancer. A 53-year-old man, receiving pembrolizumab for invasive bladder cancer, developed erythematous papules on his legs after his 11th infusion. The skin lesions gradually spread to his entire trunk and extremities. A punch biopsy revealed several apoptotic keratinocytes and spongiosis, along with perivascular and lichenoid lymphocytic infiltration with vacuolar alteration. Immunohistochemistry showed infiltration of CD4+ and CD8+ T-cells in both the epidermis and dermis. Granzyme B-positive inflammatory cells were also slightly present. From these results, he was diagnosed with PLEVA, which might be classified as a lichenoid eruption, especially based on the histological findings.

Conclusion
We hypothesize that the anti-PD-1 antibody might lead to epidermal necrosis by amplifying the expression of cytolytic molecules such as granzyme B in CD8+T cells.