An unresectable cholangiolocarcinoma diagnosed by integrating biopsy-based histopathology and genomic findings with clinical and imaging data.

Cholangiolocarcinoma is a rare malignant liver tumor typically diagnosed on pathological evaluation of surgically resected specimens. Establishing a definitive diagnosis in unresectable cases is therefore challenging. A case of a large unresectable liver tumor, extending across the hepatic hilum into both lobes, is presented. Despite the advanced stage, the patient's serum total bilirubin and carbohydrate antigen 19-9 levels remained within normal ranges. On dynamic computed tomography, characteristic imaging features of CLC, including intrahepatic vessel penetration, were seen. Histopathologically, the biopsied specimen demonstrated the typical architecture of CLC, with tubular or cord-like glands with an antler-like anastomosing pattern within abundant fibrous stroma. Next-generation sequencing performed postmortem identified a somatic mutation in the isocitrate dehydrogenase 1 (IDH1) gene, previously reported to be enriched in CLC. Although the liver tumor was unresectable, integration of histopathological, genomic, clinical, and imaging findings strongly supported a diagnosis of CLC.