The first report of biliary NUT carcinoma with a fatal outcome.

Objective: NUT carcinoma (NC) is a rare epithelial malignancy caused by a rearrangement of the nuclear protein in testis gene (NUTM1), with fewer than 200 cases reported worldwide to date. The majority of cases have occurred in young patients (ie, ≤25 years of age), most commonly in the thoracic and head and neck regions. This case marks the first documented occurrence of NC in the hepatobiliary system.

Methods: A 35-year-old woman presented with abdominal pain radiating to the back that has persisted for 2 weeks. Liver tests revealed obstructive jaundice. An abdominal magnetic resonance imaging scan demonstrated diffuse intrahepatic bile duct dilatation resulting from a stricture at the biliary confluence. Subsequent endoscopic retrograde cholangiopancreatography biopsy confirmed an invasive, poorly differentiated carcinoma, and a stent was placed in the left hepatic duct. Following right portal vein embolization, the patient underwent an extended right hepatectomy.

Results: Pathology revealed a firm 2.5-cm gray-white mass at the hepatic duct bifurcation. The initial diagnosis was a biliary carcinoma characterized by mass formation and a periductal infiltrating pattern. The tumor exhibited distinctive features, such as nested architecture, open vesicular chromatin, focal squamous differentiation, and perineural vascular invasion. Positive immunohistochemistry for CK7, CK19, P40, P63, and NUT protein and identification on DNA sequencing of a BRD3::NUTM1 fusion led to a final diagnosis of NC. Despite adjuvant chemotherapy, the patient succumbed to recurrent disease 18 months after surgery.

Conclusions: This case highlights the importance of recognizing NC in atypical locations and emphasizes the need for a thorough investigation in young patients with malignancies that display squamous differentiation. This report expands our understanding of biliary NC and underscores the challenges associated with its diagnosis and management.