Transcriptomic Analysis of Cirrhosis-Like Hepatocellular Carcinoma Reveals Distinct Molecular Characteristics and Pathologic Staging Implications

Benjamin J. Van Treeck, Roger K. Moreira, Taofic Mounajjed, Linda Ferrell, Yue Xue, Erik Jessen, Jaime Davila, Rondell P. Graham

Research output: Contribution to journalArticlepeer-review


Objectives: Cirrhosis-like hepatocellular carcinoma (CL-HCC) is a rare hepatocellular malignancy characterized by multiple tumor nodules that clinically, radiologically, macroscopically, and microscopically mimic cirrhosis. We aimed to elucidate the molecular biology of CL-HCC and determine tumor nodule clonality. Methods: We performed RNA sequencing on formalin-fixed, paraffin-embedded tissue from confirmed CL-HCC cases (n = 6), along with corresponding nonneoplastic hepatic tissue (n = 4) when available. Transcriptomes from our previous work on steatohepatitic hepatocellular carcinoma and The Cancer Genome Atlas (TCGA) were used for comparison purposes. Results: Histologically, CL-HCC displayed innumerable nodules and extensive vascular invasion. Intratumoral nodule comparison indicated that the multiple nodules were all clonally related, not independent primaries. The unique histomorphologic appearance corresponded with a distinct transcriptome compared with other HCCs, including fibrolamellar HCC (n = 6), steatohepatitic HCC (n = 8), and conventional HCC in TCGA (n = 424). Tumor-normal gene expression analysis revealed consistent overexpression of several genes involved in degradation of tissue matrix. No recurrent translocations or point mutations were identified. CL-HCC showed a gene expression profile indicative of zone 2 hepatocytes. Conclusions: CL-HCC's distinctive clinicopathologic features correspond to a unique gene expression profile, increased expression of invasive markers, features of zone 2 hepatocytes, and features suggestive of intratumoral nodule monoclonality.

Original languageEnglish (US)
Pages (from-to)750-758
Number of pages9
JournalAmerican journal of clinical pathology
Issue number6
StatePublished - Dec 1 2022


  • Cirrhosis-like hepatocellular carcinoma
  • Staging
  • Transcriptomic analysis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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