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

Area of Science:

• Oncology
• Immunology
• Gastroenterology
• Hepatology

Background:

• Immune checkpoint inhibitors (CPIs) represent a significant advancement in treating advanced malignancies, improving patient survival rates.
• CPIs function by blocking coinhibitory receptors on T cells, thereby stimulating an anti-tumoural immune response.
• A notable side effect of CPIs is the occurrence of immune-related adverse events (irAEs), stemming from disrupted self-tolerance and immune-mediated processes.

Purpose of the Study:

• To provide pathologists with a comprehensive understanding of the histological findings associated with gastrointestinal (GI) and hepatic irAEs induced by CPI therapy.
• To highlight the clinical features, histopathological characteristics, management strategies, and differential diagnoses for these irAEs.
• To emphasize the importance of accurate diagnosis for optimal patient care as CPI use expands.

Main Methods:

• Review of clinical features associated with CPI-induced GI and hepatic irAEs.
• Detailed analysis of histopathological findings in GI and liver biopsies from patients treated with CPIs.
• Discussion of differential diagnoses to distinguish CPI-induced irAEs from other conditions.
• Outline of current management approaches for these adverse events.

Main Results:

• CPIs, including CTLA-4, PD-1, and PD-L1 inhibitors, can lead to significant irAEs in the GI tract and liver, manifesting as colitis or hepatitis.
• Accurate histopathological assessment of biopsies is crucial for diagnosing CPI-induced colitis and hepatitis.
• Pathologists must be aware of the spectrum of histological changes and potential mimics to ensure correct diagnosis and patient management.

Conclusions:

• The expanding use of CPIs necessitates increased pathologist awareness of GI and hepatic irAEs.
• Distinguishing CPI-induced irAEs from other pathologies through detailed histopathological examination is critical.
• Effective management of these irAEs relies on accurate diagnosis informed by understanding the specific histological patterns.