Not What it Seems: Colitis and Pseudopolyp Turn Out To Be Immune Checkpoint Inhibitor Colitis and Metastatic Renal Cell Carcinoma

Background: Immunotherapy is the first-line treatment for metastatic clear cell renal cell carcinoma (RCC). The checkpoint inhibitor combination of nivolumab plus ipilimumab is the standard of care for intermediate- and poor-risk patients. The most frequently reported GI immune-related adverse event is immune checkpoint inhibitor (ICI) colitis. Combination nivolumab plus ipilimumab is associated with an increased risk of developing ICI colitis and progression to severe colitis, as are higher doses of these therapies. Symptoms can vary in severity and raise a diagnostic challenge as histopathology alone cannot distinguish ICI colitis from inflammatory bowel disease (IBD). Methods: A 77-year-old man with a history of ICI colitis and metastatic renal cell carcinoma previously treated with combination nivolumab plus ipilimumab currently on nivolumab maintenance therapy (480 mg every 4 weeks) presented to the GI clinic for further evaluation of recurrent severe diarrhea, hematochezia, abdominal pain, and fevers. Initial workup revealed a negative GI pathogen panel and elevated fecal calprotectin at 553 mcg/g. CT abdomen with IV contrast demonstrated active inflammation involving the splenic flexure superimposed on a background of chronic colitis. His symptoms responded to cholestyramine and loperamide and nivolumab was held. He underwent a colonoscopy which showed moderate patchy inflammation characterized by congestion, erosions, erythema, granularity, and loss of vascularity in the colon with a normal terminal ileum. A 7mm non-bleeding solitary inflammatory sessile polyp seen in the cecum was removed with a cold snare. The polyp was highly vascular and required three hemostatic clips and hemostatic spray for successful hemostasis. Pathology ultimately showed involvement of metastatic renal cell carcinoma and IHC staining was immunoreactive with PAX8 and keratin. Random colon biopsies showed patchy moderate active chronic colitis consistent with ICI. Given evidence of progression of RCC suggesting failed response to nivolumab he was transitioned to cabozantinib, a small molecule tyrosine kinase inhibitor. This was associated with improvement in his symptoms of diarrhea and decrease in fecal calprotectin. Results: At follow up in IBD clinic his diarrhea was felt to be secondary to ICI colitis given improvement in symptoms and inflammatory markers after cessation of nivolumab. Plans are for serial fecal calprotectin monitoring until complete normalization with a recommendation to start prophylactic vedolizumab should he require ICI therapy in the future. Conclusions: Our case presents a unique manifestation of metastatic RCC as a polyp which endoscopically appeared as an ulcerated pseudopolyp during colonoscopy for evaluation of ICI colitis.