Abstract
BACKGROUND AND AIMS: Collagenous colitis is a rare complication of immunotherapy for cancer. We report here 15 cases in order to assess the role of immune checkpoint inhibitors (ICI) in the onset of this disease, describe the histopathological and immunological features of this entity and compare them with 'idiopathic' collagenous colitis. METHODS: We retrospectively checked for all diagnoses of collagenous colitis from 2000 to 2024 in our tertiary cancer centre. Clinical charts and the available histopathological material were reviewed. Immunohistochemical profiling was performed to characterize immune cell populations (CD3, CD4, CD8, CD20, CD68, CD163, CD117, PD1 and PD-L1). A control group of 14 patients without cancer history was included for comparison. RESULTS: Fifteen cases, diagnosed between 2017 and 2024, were included in the study group. There were nine male and six female, aged 23-81. Fourteen were treated by ICI (anti-PD1/PD-L1 in 13 cases, anti-CTLA4 in 1), 1 by daratumumab. All presented chronic diarrhoea. The typical histological features of collagenous colitis were present: sub-epithelial band of thickened extracellular matrix, expansion of the lamina propria. The predominant immune cell population was CD8+ T-lymphocytes in 12 cases. ICI-treated patients showed higher neutrophilic infiltration, including crypt abscesses and higher macrophage amounts than control patients. CONCLUSION: Collagenous colitis in patients treated for cancer is closely associated with the use of anti-PD1/PD-L1 antibodies and shows some distinctive characteristics. A further understanding of the consequences of the PD1/PD-L1 axis blockade may shed further light on the pathogenesis of this rare disease.