Histopathological and immunohistochemical features of cutaneous and oral immune-related adverse events associated with programmed cell death protein 1 inhibitor therapy

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Mucocutaneous reactions are among the most frequent and earliest immune-related adverse events (irAEs) secondary to programmed cell death protein 1 (PD-1) inhibitor treatment, often resembling autoimmune or immune-mediated disorders. Despite their prevalence, biopsies of irAEs are infrequently performed, resulting in limited data on their histopathological and immunohistochemical findings. We evaluated the histopathological and immunohistochemical features of irAEs in seven patients with cancer treated with pembrolizumab (n = 5) or nivolumab (n = 2). Four patients had lichenoid reactions, while a sarcoid-like reaction, a psoriasis-like reaction and Stevens-Johnson syndrome occurred in one patient each. A predominantly lymphocytic inflammatory infiltrate adjacent to the surface epithelium and the presence of apoptotic keratinocytes were the most frequent histopathological characteristics. High immunoreactivity was observed for CD3, CD4 and CD68, and all patients were negative for CD30. Histopathological and immunohistochemical characterization of irAEs may aid in differential diagnosis and management of PD-1 inhibitor-induced reactions.

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