Metastatic Fibrolamellar Hepatocellular Carcinoma in a Young Adult: A Case Report and Narrative Review

Abstract: Fibrolamellar hepatocellular carcinoma (FLC) is a rare and distinct histologic subtype of hepatocellular carcinoma that typically arises in non-cirrhotic livers of adolescents and young adults without underlying viral hepatitis or chronic liver disease. Accounting for less than 1% of all primary liver cancers, FLC is characterized by unique clinical, radiologic, and molecular features, most notably the highly characteristic DNAJB1–PRKACA fusion. Due to its rarity and frequently nonspecific presentation, diagnosis is often delayed or misinterpreted as by benign hepatic lesions such as focal nodular hyperplasia or adenoma. This report presents a rare case of metastatic FLC in a young adult who initially presented with right upper quadrant pain, anemia, and preserved hepatic function. Imaging revealed a large hepatic mass with a central non-enhancing area suggestive of necrosis, and histopathologic evaluation aided in the diagnosis based on characteristic lamellar fibrosis, polygonal eosinophilic cells, and positive CK7 and HepPar-1 staining. Confirmatory molecular testing through DNAJB1–PRKACA fusion was not performed. Planned treatment with a combination regimen of nivolumab and neratinib was scheduled; however, the patient deteriorated rapidly, and systemic therapy could not be initiated before death. Through this case and accompanying review, we aim to highlight the diagnostic complexity, molecular underpinnings, and current therapeutic approaches of FLC. This case was notable for advanced peritoneal carcinomatosis at presentation, severe thrombocytosis, and the diagnostic and therapeutic challenges posed by metastatic fibrolamellar carcinoma without molecular confirmation. Taken together, this underscores the importance of early recognition, molecular testing, and coordinated clinical management in optimizing outcomes for this uncommon malignancy. Keywords: fibrolamellar hepatocellular carcinoma, liver cancer, case report, pathogenesis, diagnosis, treatment, immunotherapy