Dermatologic toxicities to immune checkpoint inhibitor therapy: A review of histopathologic features

Abstract

Antineoplastic agents that use the immune system have revolutionized cancer treatment. Specifically, implementation of immune checkpoint inhibitors, monoclonal antibodies that block cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein 1, or programmed cell death ligand 1 show improved and sustained responses in patients with cancer. However, these agents are associated with a plethora of adverse events, many manifesting in the skin. As the clinical application of cancer immunotherapies expands, understanding the clinical and histopathologic features of associated cutaneous toxicities becomes increasingly important to dermatologists, oncologists, and pathologists to ensure timely diagnosis and appropriate care. This review discusses cutaneous reactions to immune checkpoint inhibitors, focusing on histopathologic features.

Keywords: CTLA-4; PD-L1; PD1; adverse event; atezolizumab; avelumab; bullous pemphigoid; checkpoint inhibitor; cutaneous; durvalumab; immunotherapy; ipilimumab; lichenoid dermatitis; nivolumab; pembrolizumab; rash; skin; toxicity.

Figure 1.

Bullous lichenoid dermatitis secondary to nivolumab. Biopsy shows a band-like lymphocytic infiltrate associated with a cleft formation at the dermal-epidermal junction.

Figure 2.

Bullous pemphigoid secondary to pembrolizumab. Biopsy shows perivascular eosinophils and vacuolar alteration along the junction. Bullae were not present histologically in the biopsy specimen. DIF showed deposition of C3 and IgG along the junction (not shown). Clinically, the patient had intact and eroded bullae on erythematous base.