Introduction
Immune-related adverse events (irAEs) are a significant concern in the field of immunotherapy, particularly with the use of immune checkpoint inhibitors for cancer treatment. These adverse events are due to the activation of the immune system, which can mistakenly target normal tissues. Understanding the histological changes associated with irAEs is crucial for their diagnosis and management.What are Immune-Related Adverse Events?
Immune-related adverse events are side effects that occur when the immune system, activated by immunotherapy, attacks normal cells in the body. These can affect various organs, including the skin, gastrointestinal tract, liver, endocrine glands, and lungs. Histologically, these events can manifest in different patterns depending on the affected organ and the type of immune response involved.
Histological Features of irAEs
Skin
The skin is one of the most commonly affected organs. Histological examination often reveals a
lichenoid dermatitis, characterized by interface dermatitis with basal keratinocyte damage, vacuolar changes, and a dense lymphocytic infiltrate. Other patterns include spongiotic dermatitis and
psoriasiform dermatitis.
Gastrointestinal Tract
In the gastrointestinal tract, irAEs often present as colitis. Histologically, this can be seen as an increase in intraepithelial lymphocytes, crypt abscesses, and crypt apoptosis. The inflammation is usually rich in
neutrophils and can resemble other forms of inflammatory bowel disease such as ulcerative colitis or Crohn's disease.
Liver
Hepatic irAEs typically manifest as
hepatitis. Biopsy samples often show lobular and portal inflammation with a predominance of lymphocytes and plasma cells. Hepatocyte injury is indicated by ballooning degeneration and apoptosis.
Endocrine Glands
Endocrine irAEs can affect the thyroid, pituitary, and adrenal glands. Thyroiditis is common and histologically shows a diffuse lymphocytic infiltrate. The pituitary gland may exhibit lymphocytic hypophysitis, characterized by infiltration of lymphocytes and plasma cells, which can lead to glandular atrophy.
Lungs
Pneumonitis is a potentially severe irAE affecting the lungs. Histologically, it can present as organizing pneumonia, diffuse alveolar damage, or lymphocytic interstitial pneumonitis. The lung tissue may show interstitial fibrosis and a mixed inflammatory infiltrate.
Diagnosis and Management
Diagnosis of irAEs involves a combination of clinical presentation, imaging studies, and histological examination of biopsy samples. Early recognition and intervention are crucial to prevent severe complications. Management typically includes
corticosteroids and other immunosuppressive agents to mitigate the immune response.
Conclusion
Immune-related adverse events are a complex and critical aspect of immunotherapy. Histological examination provides valuable insights into the nature and extent of tissue damage, guiding appropriate management strategies. As immunotherapy continues to evolve, understanding the histopathological features of irAEs will remain essential for optimizing patient outcomes.
