Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree, leading to significant liver function impairment over time. There is a strong association with inflammatory bowel diseases (IBD), together representing a distinct and complex medical condition. Patients with PSC-IBD face a heightened risk of various cancers, particularly colorectal carcinoma (CRC) and cholangiocarcinoma (CCA) as the most common types. In this review, we aim to characterize the distinctive features of PSC-IBD-associated carcinomas. Cancer pathogenesis in PSC-IBD is shaped by various factors including dysregulated bile acid metabolism, gut dysbiosis, and unique immune responses. PSC-IBD-associated CRC is often right-sided and warrants vigilant monitoring due to its higher incidence and unique morphological features compared to CRC arising in the terrain of IBD alone. CCA shares substantial genetic similarities with extrahepatic CCA and poses diagnostic challenges since it is frequently detected at advanced stages due to symptom overlap with PSC. Besides, reliable predictive biomarkers for targeted therapy remain largely unexplored. The distinct molecular, genetic, and histopathological profiles of CRC and CCA in PSC-IBD underscore the complexity of these malignancies and highlight the need for continued research to develop precise therapeutic strategies.

Clinical and Transplant Pathology Centre Institute for Clinical and Experimental Medicine Prague 14021 Czech Republic

Department of Gastroenterology and Hepatology Institute for Clinical and Experimental Medicine Prague 14021 Czech Republic

Department of Internal Medicine 2nd Faculty of Medicine Charles University Prague 15000 Czech Republic

Department of Pathology and Molecular Medicine 3rd Faculty of Medicine Charles University and Thomayer Hospital Prague 14059 Czech Republic

Department of Pathology Royal Vinohrady Teaching Hospital Srobarova 1150 50 Prague 10000 Czech Republic

Experimental Medicine Centre Institute for Clinical and Experimental Medicine Prague 14021 Czech Republic

Institute of Pathology of the 1st Faculty of Medicine and General Teaching Hospital Prague 12800 Czech Republic

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