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15TH INTERNATIONAL GASTROINTESTINAL CANCERS CONFERENCE, Antalya, Turkey, 4 - 07 December 2025, pp.30, (Full Text)
COMBINED HEPATOCELLULAR– CHOLANGIOCARCINOMA: A RARE AND THERAPEUTICALLY CHALLENGING LIVER MALIGNANCY Mustafa Ersoy, Selin Meşeli, Ismet Çulcuoğlu Kütahya Sağlık Bilimleri Üniversitesi Tıp Fakültesi, İç Hastalıkları Ana Bilim Dalı, Kütahya Background: Combined hepatocellular–cholangiocarcinoma (cHCC–CCA) is an uncommon primary liver malignancy containing both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) components within the same tumor. It accounts for approximately 3–5% of all primary liver cancers and generally carries an aggressive clinical course with limited therapeutic options. We report a patient with histologically proven cHCC–CCA who underwent locoregional and systemic treatments but showed poor response and short survival. Case Presentation: A 68-year-old male with a history of hypertension and type 2 diabetes mellitus, but no evidence of chronic liver disease or viral hepatitis, presented in 2023 with fatigue and right upper quadrant discomfort. Laboratory results revealed mildly elevated transaminases; AFP and CA19-9 were within near-normal limits. Hepatitis B and C serologies were negative. Magnetic resonance imaging demonstrated multiple heterogeneous lesions involving both hepatic lobes with arterial enhancement and venous washout. Liver biopsy revealed a combined hepatocellular–cholangiocarcinoma, with areas positive for HepPar-1 and glypican-3 consistent with HCC and glandular areas positive for CK7/CK19 consistent with iCCA differentiation.Given multifocal disease and lack of surgical resectability, the patient initially underwent transarterial chemoembolization (TACE) for local control. After transient stabilization, disease progression was noted at 4 months. Subsequently, systemic chemotherapy with cisplatin and gemcitabine was administered for two cycles without radiologic or clinical response. Due to deterioration in performance status and hepatic function, further therapy was discontinued, and the patient was managed with best supportive care. He died approximately 8 months after diagnosis. Discussion: cHCC–CCA represents a unique subtype of primary liver cancer with dual histologic and molecular features. The absence of cirrhosis in this case suggests a de novo origin from hepatic progenitor cells. Prognosis remains poor because of early intrahepatic spread and resistance to conventional therapies. While surgical resection offers the best outcomes, most cases are diagnosed at an unresectable stage. Locoregional therapies such as TACE may provide temporary disease control, whereas systemic chemotherapy with gemcitabine and cisplatin or targeted agents generally yields limited benefit. Novel systemic approaches, including immunotherapy combinations, are under investigation. Conclusion: cHCC–CCA should be considered in patients with atypical imaging and mixed histopathological findings. Despite multimodal treatment including TACE and chemotherapy, prognosis remains poor. Multicenter studies and molecularly guided therapies are needed to improve outcomes in this rare and aggressive malignancy. Keywords: combined hepatocellular–cholangiocarcinoma, cisplatin– gemcitabine, TACE