A. P. Huynh1, M. L. Kueht2, A. Rana2, D. Lopez-Terrada3, J. Goss2 1Baylor College Of Medicine,Houston, TX, USA 2Baylor College Of Medicine,Michael E. DeBakey Department Of Surgery, Division Of Abdominal Transplantation,Houston, TX, USA 3Baylor College Of Medicine,Department Of Pathology And Immunology; Department Of Pediatrics,Houston, TX, USA
Introduction: Hepatoblastoma (HB), the most common liver malignancy in children, generally presents in children under 3 years of age. Current standards for profiling risk in pediatric HB are based on tumor histologic appearance, coarse patient demographics (age at time of diagnosis), and circulating alpha fetoprotein (AFP) levels. In the era of personalized medicine, identification of a tumor’s genetic markers can reveal valuable therapeutic targets. FGF19 functions as a growth factor for liver cells and FGF19 gene amplification has been shown to act as a driver for adult hepatocellular carcinoma (HCC), but its role in HB is unknown. Here, we describe the first reported discovery of increased FGF19 copy number in a pediatric patient with aggressive HB.
Methods: The patient’s medical records were reviewed to obtain the clinical course, and whole genome sequencing of the patient’s tumor was performed to further understand the aggressive nature of this HB.
Results: A 21-month-old male presented to our hospital with abdominal pain and elevated AFP levels. Liver biopsy confirmed an epithelial HB and MRI demonstrated a large multi-focal tumor involving multiple liver segments (PRETEXT IV, COG stage III). Despite initiating neo-adjuvant chemotherapy and attempting two different regiments, tumor burden and AFP continued to rise. The patient ultimately underwent orthotopic liver transplantation.
Explant histology revealed 70% tumor viability. Less than one month after transplantation, rising transaminases and elevated AFP levels prompted imaging that revealed pulmonary metastases and tumor thrombi in the superior mesenteric and portal vein. The patient died shortly after recurrence.
A mutation panel revealed a CTNNB1 missense mutation consistent with embryonal HB, corroborating the histopathological diagnosis. However, whole genome amplification analysis identified amplifications in a region of chromosome 11 corresponding to FGF19, an oncogene associated with adult HCC but not previously tied to pediatric HB.
Conclusion: Increasing utilization of tumor genetics and experience with tumor histopathology has identified variants of HB with characteristics resembling HCC and indeed, the concept of a spectrum between these two diagnoses has been posited. This particular case study is noteworthy because it demonstrates the utility of tumor genetics in identifying prognostic markers individual to this case of HB. More importantly, the identification of increased FGF19 copy number implicates a potential role for FGF receptor kinase inhibitors in difficult to control forms of pediatric HB.
