Immune checkpoint inhibitor-induced cutaneous toxicities: a review of histopathologic and clinical features

• Published in: Human pathology Vol. 140; pp. 144 - 172
• Main Authors: Martel, Julianna, Hanania, Hannah L., Patel, Anisha B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2023
• Subjects: Checkpoint inhibitor; CTLA-4; Cutaneous; Drug rash; Immunotherapy; PD-1; PD-L1; Checkpoint inhibitor; Drug rash; Immunotherapy; PD-L1; CTLA-4; PD-1; Cutaneous
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2023.04.016

Immune checkpoint inhibitors (ICIs) represent an emerging treatment option for a variety of cancer types. Through inhibition of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and/or cytotoxic lymphocyte-associated antigen-4 (CTLA-4), ICIs activate the host's immune system causing a heightened anti-tumor response. However, off-target effects of ICIs can result in numerous different immune-related cutaneous adverse events (irCAEs). Beyond impacting quality of life, irCAEs can lead to dose limitations or discontinuation of anti-cancer therapies. Correct diagnosis is necessary for expedient and appropriate management. Skin biopsies are often performed to increase diagnostic accuracy and guide clinical management. An extensive literature review was performed using the PubMed database to identify the reported clinical and histopathologic features of irCAEs. This comprehensive review primarily details the histopathologic features of various irCAEs reported to date. Clinical presentation and immunopathogenesis are also discussed in relation to histopathology. •Checkpoint inhibitors are an efficacious treatment method for a variety of cancer types.•Immune-related cutaneous toxicities may be dose-limiting and impact quality of life.•Timely diagnosis is necessary to reduce interruption of anti-cancer therapies.•Skin biopsy and histopathology are key diagnostic tools to guide clinical management.