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A) Intranuclear inclusion body within the circle (× 60).B) Immunohistochemical staining with anti-cytomegalovirus antibody (× 40).tive against cytomegalovirus gastritis.Written informed consent was obtained from the patient.DiscussionImmune checkpoint inhibitors are monoclonal antibodies that block inhibitors of T-cell activation and may cause autoimmune manifestations. The incidence of colitis in patients treated with anti-pro-grammed cell death 1/PD-L1 (anti-PD-1/PD-L1) therapy is <5%1). Any grade irAEs have been reported to occur 32.9% of lung cancer patients treated with pembrolizumab2). In this case, time on pembrolizmab prior to diarrhea was 10days; shorter than median time from PD-1 inhibitor initiation to irAE onset was 3months3). The cause might be the first-line durvalumab.The endoscopic findings of intestinal irAE resemble those of ulcerative colitis4). Inflammatory changes in the entire colon, as noted in the present case, can be observed in patients with inflammatory bowel disease or infectious disease. The morphological changes associated with intestinal irAE are classified into four catego-ries, namely active colitis with apoptosis, lympho-cytic colitis, acute self-limiting colitis, and collage-nous colitis5, 6). The histopathologic differential diagnoses of intestinal irAE include inflammatory bowel disease, infectious disease, and other thera-peutic effects4, 5). Intraepithelial CD8-positive lympho-cytosis is a key component in the pathogenesis of irAEs7).The development of an irAE in immunosuppressed patients is associated with cytomegalovirus infec-396Figure 4 Atypical mesenchymal cells in gastric mucosaABtion. Although there are some theories8-10), the risk of SARS-CoV-2 infection in patients receiving immune checkpoint inhibitors is currently unclear. A study demonstrated that the use of corticoste-roids and/or anti-TNF drugs was a major risk factor for the development of infection among patients with melanoma who received immune checkpoint inhibitors11). In this case, it appears that the immunosuppressive agents contributed to SARS-CoV-2 and cytomegalovirus infection. Rectal biopsy using immunohistochemistry, performed at the time of discontinuation of prednisolone or inflix-imab, was negative for cytomegalovirus. Cytomeg-alovirus infection should be considered in cases in which a patient with an irAE develops resistance to immunosuppressive therapy. Eroded or cyto-megalovirus-infected mucosa sometimes revealed atypical mesenchymal cells which should be distinct from malignancy. The distinction between gastro-intestinal irAE and infection is important, because the treatment modalities for these conditions differ considerably. Sufficient clinical information is warranted for accurate pathological diagnosis.As shown in this report, gastric irAE and cyto-megalovirus infection can occur simultaneously during the treatment of colonic irAE. Hence, we should take notice of complication of irAEs and virus infection.Not applicable.Acknowledgments

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