Genetic and epigenetic basis of hepatoblastoma diversity

Hepatoblastoma (HB) is the most common pediatric liver malignancy; however, hereditary predisposition and acquired molecular aberrations related to HB clinicopathological diversity are not well understood. Here, we perform an integrative genomic profiling of 163 pediatric liver tumors (154 HBs and nine hepatocellular carcinomas) based on the data acquired from a cohort study (JPLT-2). The total number of somatic mutations is precious low (0.52/Mb on exonic regions) but correlated with age at diagnosis. Telomerase reverse transcriptase (TERT) promoter mutations are prevalent in the tween HBs, selective in the transitional liver cell tumor (TLCT, > 8 years old). DNA methylation profiling reveals that classical HBs are characterized by the specific hypomethylated enhancers, which are enriched with binding sites for ASCL2, a regulatory transcription factor for definitive endoderm in Wnt-pathway. Prolonged upregulation of ASCL2, as well as fetal-liver-like methylation patterns of IGF2 promoters, suggests their “cell of origin” derived from the premature hepatoblast, similar to intestinal epithelial cells, which are highly proliferative. Systematic molecular profiling of HB is a promising approach for understanding the epigenetic drivers of hepatoblast carcinogenesis and deriving clues for risk stratification.

Malignant Rhabdoid Tumor, an Aggressive Tumor Often Misclassified as Small Cell Variant of Hepatoblastoma

The clinical management of pediatric liver tumors involves stratification into risk groups. One previously defined, high-risk group of hepatoblastomas is the small cell undifferentiated variant. In light of molecular studies showing SMARCB1 deletion in these tumors, it is now recognized that most small cell, undifferentiated liver tumors represent an aggressive unrelated tumor—the malignant rhabdoid tumor (MRT). SMARCB1 is a member of the chromatin remodeling SWI/SNF complex and encodes the INI1 protein. The histologic diagnosis of MRT is currently based on INI1 negative immunoreactivity and the presence of rhabdoid morphology. INI1-negative small cell liver tumors lacking classic rhabdoid morphology are often misclassified as small cell undifferentiated hepatoblastomas (SCUD-HB), according to the current classification. Pediatric liver tumors diagnosed between 2003–2017 as SCUD-HB (four cases) or MRT (two cases) were identified from the Columbia University Pathology Department Archives. All tumors were associated with normal or low serum alpha fetoprotein levels, and showed an absence of immunohistochemical staining of hepatocellular markers (Hep-par1, Arginase) and loss of INI1 staining. Two cases were initially diagnosed as MRT, one with prominent rhabdoid morphology, the other with predominant small cell morphology. The remaining four cases with small cell morphology were classified as SCUD-HB. Ancillary molecular studies confirmed the loss of SMARCB1, supporting the diagnosis of MRT in all cases, proving morphology an unreliable criterion. It is critical to eliminate the term INI1-negative hepatoblastoma from the current classification scheme, and classify INI1-negative tumors as MRT, particularly since high-risk HB-chemotherapy regimens are not effective for treating MRT.

HEPATOBLASTOMA: 5-YEAR RETROSPECTIVE STUDY. PEDIATRIC ONCOLOGICAL SURGERY SERVICE “GENERAL ONCOLOGY HOSPITAL.SOLÓN ESPINOSA AYALA” SOLCA QUITO- ECUADOR

Objectives: Describe the demographic variables, types of liver tumor, surgeries performed and survival children diagnosed with liver tumor undergoing surgical treatment.Method: A retrospective analysis was performed in patients with pediatric liver tumors undergoing surgical treatment, from January 2010 to December 2015 at the "General Oncology Hospital. Solon Espinoza Ayala”. Results: Data from our study reported a diagnosis of hepatoblastoma in 51.85% of all pediatric liver tumors; 50% are routine controls without evidence of disease, 14.28% have been completed clinical treatment, 21.42% died from a second primary diagnosis with metastasis, and another 14.28% (only surgery) who were not followed up because they were transfers from another health system; with respect to global survival it was 64%. The ages ranged from 0 to 15 years old with an average of 5.5. Conclusion: It is very important a timely detection and adequate treatment by a specialized center and trained professionals, liver surgery is a very important chapter for the treatment of liver tumors. The surgical approach with tumor-free resection along with multidisciplinary treatment is the goal for healing.