Pediatric Metastatic Hepatoblastoma With an ARID1A Mutation and Rhabdoid Cells

Area of Science:

• Oncology
• Molecular Pathology
• Pediatric Cancer

Background:

• Hepatoblastoma (HB) can present with an uncommon small cell undifferentiated (SCU) component, distinct from malignant rhabdoid tumors (MRT) characterized by SMARCB1 alterations.
• AT-rich interactive domain-containing protein 1A (ARID1A) mutations are drivers in hepatocellular carcinoma but their role in HB is largely unknown.

Observation:

• A unique case of HB in a 19-month-old female is presented, featuring an atypical SCU component with concurrent ARID1A and beta-catenin mutations.
• The tumor exhibited an aggressive clinical course with widespread metastases, including leptomeningeal involvement, leading to a fatal outcome despite treatment.
• Initial biopsy lacked rhabdoid cells, but autopsy specimens revealed rhabdoid morphology in metastatic foci, mimicking MRT.

Findings:

• Molecular analysis of the metastatic foci, despite rhabdoid morphology, did not reveal SMARCB1 mutations or copy number alterations, ruling out MRT.
• The presence of ARID1A mutations in this aggressive HB case suggests a potential role in tumor progression and metastasis.

Implications:

• This case highlights the importance of comprehensive molecular profiling in distinguishing HB subtypes and understanding aggressive behavior.
• The findings expand the mutational landscape of hepatoblastoma and suggest ARID1A as a potential target for future therapeutic strategies.
• It underscores the diagnostic challenge posed by morphologically rhabdoid-appearing metastatic foci in HB that lack SMARCB1 alterations.