Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, with alpha-fetoprotein (AFP) being the most widely used biomarker for its diagnosis. However, AFP levels may remain normal or only minimally elevated in certain cases, such as early-stage or non-cirrhotic HCC, thereby limiting its diagnostic utility. We report the case of a 75-year-old obese male who presented with an atypical form of HCC characterized by normal AFP levels and markedly elevated carbohydrate antigen 19-9 (CA19-9), a tumor marker typically associated with gastrointestinal malignancies. The patient had no history of viral hepatitis or liver cirrhosis and initially complained of mild abdominal discomfort. Laboratory tests revealed normal AFP levels, while abdominal ultrasonography detected no suspicious hepatic lesions. Due to persistently elevated CA19-9 levels, an abdominal contrast-enhanced computed tomography scan was performed, revealing a hypervascular lesion in hepatic segment 7 (S7), consistent with HCC. The patient subsequently under-went S7 hepatectomy and experienced an uneventful postoperative recovery. Histopathological examination confirmed moderately differentiated HCC. This case underscores the diagnostic challenge posed by HCC presenting with normal AFP and elevated CA19-9 levels, particularly in non-viral, non-cirrhotic patients. It highlights the importance of considering additional or alternative biomarkers in such atypical presentations. Although CA19-9 is not routinely used in the diagnosis of HCC, its elevation in certain older patients may suggest a potential adjunctive role, meriting further investigation into its diagnostic and prognostic significance in HCC.
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