Molecular profiling in paediatric hepatocellular adenomas: phenotypic correlations and clinical significance.

Abstract

Aims: Hepatocellular adenomas (HCAs) are rare in children and often arise in distinct clinical contexts, despite sharing classification frameworks with adult cases. This series evaluates the clinicopathologic features of HCAs in patients 21 years or younger, highlighting phenotype-genotype correlations and the clinical relevance of molecular testing.

Methods and results: 27 HCAs from 26 patients (69% female; mean age: 16.2 years) were analyzed. Based on morphology and immunohistochemistry (IHC), most cases were unclassified (46%), followed by inflammatory (35%), HNF1A-inactivated (15%) and β-catenin-activated (4%) subtypes. Most patients (69%) had multifocal disease. In addition to classic risk factors such as oral contraceptive use and obesity, 35% had a history of neoplasm and 15% had glycogen storage disease. Next-generation sequencing was performed on 13 HCAs; germline testing was available in 1 patient with familial adenomatous polyposis. While molecular testing had limited impact on reclassification, it was valuable in cases with ambiguous IHC profiles and in guiding management of patients with atypical or syndromic presentations by excluding variants associated with malignant potential.

Conclusions: Paediatric HCAs arise in diverse clinical contexts and may require individualized treatment planning. While histologic and immunophenotypic evaluation is sufficient in most cases, molecular profiling adds value in diagnostically challenging scenarios and may help guide management decisions.