Genomic analysis of focal nodular hyperplasia with associated hepatocellular carcinoma unveils its malignant potential: a case report

局灶性结节性增生与相关肝细胞癌的基因组分析揭示其恶性潜能:病例报告

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作者:Caner Ercan #, Mairene Coto-Llerena #, John Gallon #, Lana Fourie, Mattia Marinucci, Gabriel F Hess, Jürg Vosbeck, Stephanie Taha-Mehlitz, Tuyana Boldanova, Marie-Anne Meier, Alexandar Tzankov, Matthias S Matter, Martin H K Hoffmann, Luca Di Tommaso, Markus von Flüe, Charlotte K Y Ng, Markus H Heim,

Background

Focal nodular hyperplasia (FNH) is typically considered a benign tumor of the liver without malignant potential. The co-occurrence of FNH and hepatocellular carcinoma (HCC) has been reported in rare cases. In this study we sought to investigate the clonal relationship between these lesions in a patient with FNH-HCC co-occurrence.

Conclusion

To the best of our knowledge, our work is the first study showing a clonal relationship between FNH and HCC. We show that FNH may possess the capability to undergo malignant transformation and to progress to HCC in very rare cases.

Methods

A 74-year-old female patient underwent liver tumor resection. The resected nodule was subjected to histologic analyses using hematoxylin and eosin stain and immunohistochemistry. DNA extracted from microdissected FNH and HCC regions was subjected to whole exome sequencing. Clonality analysis were performed using PyClone.

Results

Histologic analysis reveals that the nodule consists of an FNH and two adjoining HCC components with distinct histopathological features. Immunophenotypic characterization and genomic analyses suggest that the FNH is clonally related to the HCC components, and is composed of multiple clones at diagnosis, that are likely to have progressed to HCC through clonal selection and/or the acquisition of additional genetic events.

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