An unusual presentation of Hepatocellular Carcinoma: Isolated bile duct involvement without detectable hepatic mass.

Hepatocellular carcinoma (HCC) represents the most common primary malignancy of the liver and typically arises in the setting of liver cirrhosis, most frequently secondary to chronic viral hepatitis. We describe an atypical presentation of HCC in a patient with chronic hepatitis C and advanced cirrhosis, characterized by the absence of a detectable hepatic mass lesion on imaging. Definitive diagnosis was achieved only through endoscopic retrograde cholangiopancreatography (ERCP) with direct cholangioscopy and targeted biopsy of the bile duct. Histopathological evaluation, supported by immunohistochemical staining demonstrating glypican-3 expression and p53 overexpression, confirmed the diagnosis of hepatocellular carcinoma. Given the advanced stage of disease, systemic immunotherapy with tremelimumab and durvalumab was initiated. This case underscores the critical role of a multimodal diagnostic approach in atypical presentations of HCC to enable accurate diagnosis and appropriate therapeutic decision-making.