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Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective
  1. Dipti M Karamchandani1,
  2. Runjan Chetty2
  1. 1Division of Anatomic Pathology, Department of Pathology, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, USA
  2. 2Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
  1. Correspondence to Dr Dipti M Karamchandani, Division of Anatomic Pathology, Department of Pathology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA; dkaramchandani{at}pennstatehealth.psu.edu

Abstract

Immune checkpoint inhibitors (CPIs) are a relatively new class of ‘miracle’ dugs that have revolutionised the treatment and prognosis of some advanced-stage malignancies, and have increased the survival rates significantly. This class of drugs includes cytotoxic T lymphocyte antigen-4 inhibitors such as ipilimumab; programmed cell death protein-1 inhibitors such as nivolumab, pembrolizumab and avelumab; and programmed cell death protein ligand-1 inhibitors such as atezolizumab. These drugs stimulate the immune system by blocking the coinhibitory receptors on the T cells and lead to antitumoural response. However, a flip side of these novel drugs is immune-related adverse events (irAEs), secondary to immune-mediated process due to disrupted self-tolerance. The irAEs in the gastrointestinal (GI) tract/liver may result in diarrhoea, colitis or hepatitis. An accurate diagnosis of CPI-induced colitis and/or hepatitis is essential for optimal patient management. As we anticipate greater use of these drugs in the future given the significant clinical response, pathologists need to be aware of the spectrum of histological findings that may be encountered in GI and/or liver biopsies received from these patients, as well as differentiate them from its histopathological mimics. This present review discusses the clinical features, detailed histopathological features, management and the differential diagnosis of the luminal GI and hepatic irAEs that may be encountered secondary to CPI therapy.

  • colon
  • histopathology
  • liver

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Footnotes

  • Handling editor Cheok Soon Lee.

  • Contributors Both the authors (DMK, RC) participated actively in this manuscript and can take public responsibility for the content of this paper. All authors critically revised the paper for intellectual content and have approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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