[Fibrolamellar hepatocellular carcinoma: a clinicopathological and molecular genetic analysis of nine cases]

Objective: To investigate the clinicopathological and molecular features of fibrolamellar hepatocellular carcinoma (FL-HCC). Methods: The clinicopathological and prognostic information of 9 FL-HCC cases diagnosed at the Fudan University Shanghai Cancer Center, Shanghai, China from January 2018 to December 2024 were collected and analyzed. The FL-HCC samples were examined with immunohistochemical staining, fluorescence in situ hybridization (FISH), and RNA-based next-generation sequencing (NGS). The related literature was also reviewed. Results: There were 3 males and 6 females. The patients' age was 18.0 (10.5, 26.0) years. One of the 9 patients had slightly elevated serum AFP level, and 2 patients had current infection of hepatitis B virus. Five cases occurred in the left lobe of the liver, 3 cases in the right lobe of the liver, and 1 case had multiple lesions involving both the left and right lobes. The tumor sizes ranged from 4.0 to 21.4 cm. Microscopically, neoplastic cells were mainly arranged in sheets or nests, separated by dense collagen bundles frequently arranged in cord-like or parallel lamellae. The tumor cells were large and polygonal, with abundant granular and eosinophilic cytoplasm, large vesicular nuclei, and prominent nucleoli. All tumor cells expressed CK7, HepPar-1, and Arg-1. Molecular analysis revealed that 6 cases harbored the DNAJB1::PRKACA gene fusion by NGS, while the other 3 cases showed PRKACA gene rearrangement by FISH using a break-apart probe. The follow-up period ranged from 7 to 80 months. One patient was lost to follow-up after diagnosis, 3 patients survived without recurrence, 1 patient relapsed with lung metastasis, and 4 patients died of the disease. Conclusion: FL-HCC is a rare type of hepatocellular carcinoma characterized by laminated intratumoral fibrous stroma and specific fusion (DNAJB1::PRKACA) or rearrangement of the PRKACA gene.