Cholangiocarcinoma complicating primary sclerosing cholangitis: Case report and brief literature review

Cholangiocarcinoma (CCA) is an uncommon yet highly aggressive malignancy that arises from the biliary epithelium. It is frequently observed in the setting of chronic inflammatory disorders, where ongoing epithelial injury and regeneration predispose to malignant transformation. 
We present a case of a 47-year-old man with longstanding ulcerative colitis and primary sclerosing cholangitis who presented with progressive fatigue, pruritus, jaundice, and unintentional weight loss. Laboratory evaluation and radiographic findings raised a strong suspicion of malignant transformation in the context of PSC.
Given the high pretest probability of perihilar cholangiocarcinoma (pCCA) and the inherent limitations of tissue acquisition in this anatomically complex region, a multidisciplinary consensus supported definitive surgical management. The patient underwent extensive hepatic resection with biliary reconstruction. Histopathologic analysis confirmed moderately differentiated CCA arising in a background of PSC, with high-risk features including perineural invasion and positive resection margins for invasive carcinoma. Loss of SMAD4 expression was observed, a finding associated with more aggressive tumor behavior and poorer prognosis.
The postoperative course was complicated by bile leak and cholangitis. Despite aggressive surgical intervention, early local recurrence occurred within one year, necessitating transition to palliative systemic therapy. 
This case underscores the formidable diagnostic and therapeutic challenges inherent in PSC-associated cholangiocarcinoma and highlights its aggressive clinical trajectory and poor prognosis despite timely intervention.