Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective

Abstract

<jats:p>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.</jats:p>

Pembrolizumab‐related pancreatitis with elevation of pancreatic tumour markers

“…However, certain organs, such as the kidney and colon, express PD‐L1 in epithelial cells . Furthermore, the histopathological features of anti‐PD‐1‐associated colitis indicate an active inflammation, observed as a mucosal injury with lymphocyte infiltration, increased apoptosis, and crypt atrophy and dropout , suggesting possible expression of PD‐L1 in epithelial cells of the pancreatic duct, making it a target of an immune‐related reaction.…”

Immune Response Checkpoint Inhibitors: New Risks of a New Class of Antitumor Agents

“…Колит преимущественно поражал нисходящую кишку [96]. По данным гистологических исследований, колит сопровождался отеком и нейтрофильно-лимфоцитарной инфильтрацией слизистой оболочки кишки [97,98].…”

“…У пациентов с аутоиммунным гепатитом чаще всего наблюдалось бессимптомное повышение уровня печеночных трансаминаз. Однако в научной литературе появляется все больше данных о тяжелых случаях, связанных с дисфункцией печени (гипербилирубинемия и коагулопатия), а также о редких угрожающих жизни иоНР, сопровождающихся острой печеночной недостаточностью [6,92,98,109].…”

Gross and microscopic changes of liver neoplasms and background hepatic structures following neoadjuvant therapy

“…The adverse effects profile of these agents is continuously being studied and reported. Importantly, it is known that hepatic parenchymal damage caused by hepatitis is one of the recognised injury patterns 68. Many clinical trials are ongoing to investigate the combination of kinase inhibitors with immunotherapy applying checkpoint inhibitors with promising results.…”

“…The luminal gastrointestinal tract is the most commonly affected site; however, the liver may be involved in up to 10% of patients who receive these treatments 87–90. A variety of histopathological patterns of hepatic injury have been described among the different subclasses, with the most common pattern appearing to be a panlobular hepatitis 68. Centrilobular hepatitic patterns have also been described, in addition to granulomatous hepatitis as well as a biliary pattern of injury 89 91 92.…”