Immunohistochemical analysis of lichenoid reactions in patients treated with anti-PD-L1 and anti-PD-1 therapy.

ABSTRACT

BACKGROUND: Recent advances in the immunotherapeutic treatment of cancer have led to the development of multiple new directed therapies including monoclonal antibodies that block the immune checkpoint T-cell receptor programmed death 1 (PD-1) and the PD-1 ligand, programmed death ligand 1 (PD-L1). Various immune-related toxicities have been associated with these drugs including, most commonly, skin rashes. METHODS: Five cases of lichenoid dermatitis, including one case of lichenoid mucositis and one case of lichen sclerosus, associated with anti-PD-L1 and anti-PD1 therapy were compared with three biopsies of non-drug-related lichen planus (LP) and three lichen planus-like keratoses (LPLK) used as controls. RESULTS: Histopathologic and immunophenotypic analysis of these lichenoid lesions demonstrated significantly greater histiocytic infiltrates than observed in control lichenoid reactions (p = 0.0134). We also observed increased spongiosis and epidermal necrosis. No significant differences were seen in expression of CD3, CD4CD8, CD20, PD-1, CD25, Foxp3, CXCL13 and PD-L1 expression. CONCLUSIONS: These findings expand the literature of immune-related toxicities of PD-L1 and PD-1 blockade to include lichenoid dermatitis and lichenoid mucositis. Of note, these cutaneous side effects were amenable to topical treatment, without the need for medication dose reduction or discontinuation.