S3328 An Unexpected Primary: Intrahepatic Cholangiocarcinoma Discovered During Lung Nodule Evaluation

Introduction: Cholangiocarcinoma (CCA) is a malignancy of the bile duct epithelium, classified based on its anatomic location into intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) subtypes. iCCA represents an uncommon subtype, accounting for approximately 10% of all CCA cases. While the incidence of extrahepatic CCA has remained stable, iCCA incidence has been rising in the United States. We present a case of intrahepatic cholangiocarcinoma initially discovered during the evaluation of a pulmonary nodule. Case Description/Methods: A 70-year-old woman with a medical history of hypertension, hyperlipidemia, and type 2 diabetes mellitus presented for evaluation of a persistent cough. Computed tomography scan of her chest identified a 1.9 cm spiculated mass in the right lung and a tubular soft tissue density within the right intrahepatic biliary system, raising concern for primary biliary malignancy. A positron emission tomography (PET) scan revealed hypermetabolic activity in both the hepatic and pulmonary lesions. Biopsy of the lung mass with immunohistochemical analysis was positive for cytokeratin 7 (CK7) and caudal type homeobox 2 (CDX-2). These findings were suggestive of metastasis from a gastrointestinal or pancreaticobiliary primary. Magnetic resonance imaging of the abdomen confirmed an intrahepatic cholangiocarcinoma measuring 4.6 × 2.5 × 6.1 cm with associated metastatic portocaval lymphadenopathy. The patient was started on systemic chemotherapy with a combination of cisplatin, gemcitabine, and durvalumab. Discussion: Intrahepatic cholangiocarcinoma is a relatively rare cancer that is characterized by its aggressive behavior and poor prognosis, often secondary to late-stage diagnosis. Advanced disease stages may preclude surgical resection, making chemotherapy and radiation therapy the primary treatment. Risk factors contributing to its rising incidence include chronic liver diseases (e.g., Hepatitis C, primary sclerosing cholangitis), diabetes, obesity, and tobacco use. The increasing incidence of iCCA in Western populations may reflect the rising prevalence of these underlying risk factors. This case underscores the importance of maintaining a high index of suspicion and ensuring timely diagnosis and management in patients with atypical presentations, particularly those with known metabolic or hepatic risk factors.