HER2-Positive Cholangiocarcinoma Following Previous Cervical Squamous Cell Carcinoma: A Diagnostic Challenge and Clinical Course With Sequential Systemic Therapy

Cholangiocarcinoma is an aggressive malignancy associated with poor outcomes, particularly following recurrence after surgical resection.Diagnosis can be challenging when a new hepatic lesion develops in a patient with a previous malignancy.We report the case of a 54-year-old woman with a history of stage IIB cervical squamous cell carcinoma treated with concurrent chemoradiotherapy and brachytherapy in 2020, who developed an indeterminate hepatic lesion in September 2021.A hepatic abscess was initially considered, but the lesion failed to respond to a full course of antibiotics.Biopsy demonstrated poorly differentiated adenocarcinoma, prompting investigation for an alternative primary malignancy.Upper and lower gastrointestinal endoscopy were normal, and PET-CT demonstrated a solitary avid lesion in segment 8. Right hepatectomy was performed in December 2021; histology demonstrated six lesions consistent with cholangiocarcinoma, staged pT2 Nx M0, with no lymph nodes resected.Adjuvant capecitabine was commenced based on evidence from the BILCAP trial.Shortly after surgery, CT demonstrated recurrent hepatic disease, and the patient was deemed unsuitable for further surgery or liverdirected therapy.Molecular profiling demonstrated HER2-positive, microsatellite-stable cholangiocarcinoma, with FGFR2-negative and PD-L1 CPS 0.5.Treatment for recurrent disease comprised trastuzumab with oxaliplatin-based chemotherapy, followed by trastuzumab maintenance until December 2022; gemcitabine/carboplatin for six cycles until May 2023; and FOLFIRI until August 2023.Trastuzumab deruxtecan (Enhertu) was commenced in January 2024 as a selffunded anti-HER2 treatment and discontinued in August 2024 following radiological progression.In September 2024, brain MRI demonstrated a solitary cerebral metastasis, which was treated with stereotactic radiosurgery.Palliative cisplatin was subsequently commenced.The patient died in November 2024, approximately 34 months after recurrent hepatic disease was documented.This case highlights the diagnostic challenges of distinguishing a new primary intrahepatic cholangiocarcinoma from metastatic disease, the role of HER2 testing in informing treatment options, and the clinical course of a patient who survived approximately 34 months after recurrent hepatic disease was documented.The observed survival does not establish a benefit attributable to any individual treatment.