Ziegler Paul F, Ribback Silvia
Institut für Pathologie, Universitätsmedizin Greifswald, Friedrich-Loeffler-Str. 23e, Greifswald, Deutschland.
Pathologie (Heidelb). 2025 Sep 19. doi: 10.1007/s00292-025-01467-1.
Hepatocellular carcinoma (HCC) usually arises on the background of liver cirrhosis. Common risk factors include chronic hepatitis B/C, alcohol abuse, metabolic dysfunction-associated steatotic liver disease (MASLD), and genetic disorders. Annually, 1-8% of cirrhotic patients develop HCC. According to the S3 guideline, biannual screening via ultrasound is recommended. In cirrhotic livers, high-grade dysplastic nodules (HGDN) are recognized as definite precursor lesions with high malignant transformation potential. According to the updated S3 guideline, HCC diagnosis in cirrhosis is primarily based on imaging (CT, MRI, or contrast-enhanced ultrasound): for lesions ≥ 2 cm, a typical enhancement pattern in one modality suffices; for 1-2 cm, two concordant imaging methods are required. Biopsy is only recommended in diagnostically unclear cases. In non-cirrhotic livers, however, histopathological confirmation via biopsy is mandatory due to insufficient specificity of imaging.Histologically, HCC is characterized by architectural distortion, nuclear atypia, and loss of the reticulin fiber network (Gomori stain). If malignancy criteria are inconclusive in biopsy, an immunohistochemical panel including Glypican‑3, HSP70, and glutamine synthetase can be used-expression of at least two markers strongly supports HCC diagnosis. Molecular analysis of hTERT promoter mutations may provide additional diagnostic value.Foci of altered hepatocytes (FAH) are considered putative early precursor lesions in both cirrhotic and non-cirrhotic human livers. They show increased glycogen and/or lipid accumulation, activation of the PI3K/AKT/mTOR pathway, and metabolic shifts resembling early preneoplastic changes observed in experimental hepatocarcinogenesis.