Objective:

To report a case of unresectable, multifocal ectopic hepatocellular carcinoma (EHCC) and provide insights into its genomic landscape and treatment outcomes based on comprehensive molecular profiling.

Approach:

• Case Report: A patient diagnosed with unresectable, multifocal EHCC was managed by a multidisciplinary team (MDT) and underwent comprehensive molecular profiling.
• Genomic Analysis: Whole-exome sequencing (WES) and RNA sequencing (RNA-seq) were performed to characterize the tumor's genetic and transcriptomic landscape.
• Literature Review: A systematic review of 55 reported EHCC cases was conducted to summarize demographic, clinical, management, and prognostic characteristics.

Key Findings:

• The patient achieved a progression-free survival (PFS) of 27 months and an overall survival (OS) of 30 months.
• Genomic analysis revealed significant upregulation of the interferon response pathway.
• The combination therapy of lenvatinib, camrelizumab, and stereotactic body radiotherapy (SBRT) was employed.

Interpretation:

The favorable clinical outcome associated with the multimodal treatment suggests potential therapeutic strategies for EHCC.

Limitations:

• The rarity of EHCC limits the generalizability of findings and may affect the applicability of treatment outcomes.
• The study is based on a single case report, which may not represent broader patient populations.

Conclusion:

This case provides insights into the genomic profile of EHCC and discusses the use of combination therapies for this rare disease.