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Abstract
Aims Widespread use of immune checkpoint inhibitors (ICIs) for treatment of advanced malignancies led to an increase in number of immune-related adverse events such as ICI gastrointestinal (GI) injury (ICIGI). The resulting immune dysregulation of the GI mucosa is believed to predispose patients to viral infections. We characterised the histopathological features of ICIGI and the frequency of viral infections such as cytomegalovirus (CMV), adenovirus, and Epstein-Barr virus (EBV).
Methods Single-centre retrospective study (2011–2020).
Results 81 GI biopsies from 31 patients with ICIGI (65% male (20/31), 35% female (11/31)) with advanced malignancies were reviewed. Most patients received ipilimumab and nivolumab (14/31, 45%), followed by pembrolizumab (9/31, 29%), ipilimumab (4/31, 13%), nivolumab (2/31, 6%) and combination of all three medications (2/31, 6%). Average regimen prior to incidence of diarrhea was three cycles. Evidence of colitis or erythema by endoscopy was present in 77% of cases, while 23% showed normal endoscopy. Histologically, the predominant ICIGI findings were active inflammation (84%), including cryptitis (77%), crypt abscesses (65%), lymphocytic colitis-like (LCL) pattern (61%), increase in epithelial apoptosis (74%) and/or surface injury (81%). Only one case showed diffuse CMV positivity (3%) with characteristic CMV viral cytopathic effects present on H&E stain and four cases were positive for rare EBV (13%). Adenovirus infection was not identified.
Conclusion While our cohort is small, ICIGI generally demonstrates active inflammation including cryptitis and crypt abscesses in the colon, LCL pattern, and an increase in epithelial apoptosis. Upfront immunohistochemistry for viral infection without high-degree of clinical and histologic suspicion is not recommended.
- COLITIS
- Cytomegalovirus
- Gastrointestinal Diseases
- Viruses
- Epstein-Barr Virus Infections
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Footnotes
YC and CL are joint first authors.
Handling editor Deepa T Patil.
X @YChornenkyy
Contributors Conceptualisation: YC, CL, MP. Methodology: YC, CL, MP. Investigation: YC, CL, SXDH, MP. Resources: YC, CL, MP. Data curation and analysis: YC, CL, SXDH, MP. Writing – original draft: YC, CL. Writing – review and editing: YC, CL, SXDH, JH, MP. Visualisation: YC. Supervision: MP. Funding acquisition: YC, CL, MP. Guarantor: MP.
Funding This research was supported by an institutional grant from the Northwestern University Department of Pathology Resident Research Committee.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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