Combined hepatocellular-cholangiocarcinoma: A rare and challenging diagnostic entity- A case report

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BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare and aggressive liver cancer, representing 2-5% of primary hepatic malignancies. Its mixed hepatocytic and cholangiocytic features pose major diagnostic challenges, and the absence of standardized treatment guidelines limits effective management. CASE PRESENTATION: A 61-yearold man with type 2 diabetes, hypertension, and chronic hepatitis B presented with right hypochondrial pain. Laboratory tests revealed elevated alpha-fetoprotein (247 ng/mL). Imaging showed a heterogeneous mass in liver segment V with capsular retraction, hilar lymphadenopathy, and atypical enhancement. Histological examination of the CT-guided liver biopsy suggested hepatocellular carcinoma. However, this proved to be a key diagnostic pitfall, as the complete resected specimen revealed a mixed tumor: final diagnosis of combined hepatocellularcholangiocarcinoma (cHCC-CCA) with approximately 20% hepatocellular and 80% cholangiocarcinoma components. Clinical Discussion: This case underscores the limitations of preoperative biopsy in diagnosing cHCC-CCA, highlighting the risk of misdiagnosis. Radiological features often reflect the predominant histological component but can be nonspecific due to tumor heterogeneity. Definitive diagnosis requires thorough histopathological examination with immunohistochemistry. CONCLUSIONS: cHCC-CCA poses a significant diagnostic and therapeutic challenge. Recognizing this mixed phenotype in complex liver masses is crucial. Histopathological confirmation and complete surgical resection remain key to optimal outcomes. Detailed case reports are essential to improve diagnostic criteria, elucidate molecular biology, and guide evidence-based management for this rare malignancy.