title: Natural history and treatment trends in hepatocellular carcinoma subtypes: Insights from a national cancer registry.
abstract: BACKGROUND
  Histopathologic advancements have identified several rare subtypes of hepatocellular carcinoma (HCC), but the clinical significance of these distinctions is incompletely understood. Our aim was to investigate pathologic and treatment differences between HCC variants.
  
  
  METHODS
  The American College of Surgeons National Cancer Data Base (1998-2011) was queried to identify 784 patients with surgical management of six rare HCC subtypes: fibrolamellar (FL, n = 206), scirrhous (SC, n = 29), spindle cell (SP, n = 20), clear cell (CC, n = 169), mixed type (M, n = 291), and trabecular (T, n = 69). We examined associations between demographic, tumor and treatment-specific variables, and overall survival (OS).
  
  
  RESULTS
  Patients with FL-HCC were younger than other variants (median age 27 vs. 54-61, P < 0.001), more commonly female (56.3%, P < 0.001), and less likely to receive a transplant (3.66%, P < 0.001). Patients with FL- and Sp-HCC presented more frequently with larger tumors (>5 cm, P < 0.001) and node-positive disease (P < 0.001). Better OS was associated with lower pathologic stage, node-negative disease, FL-HCC, and liver transplant. Adjuvant therapy (11% of patients) was not associated with better OS.
  
  
  CONCLUSIONS
  This largest series of recognized HCC variants demonstrates distinct differences in presentation, treatment, and prognosis. These findings can provide a valuable reference for clinicians and patients who encounter these rare clinical entities.
authors.affiliation: Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Jernigan
authors.affiliation: Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Koffi
authors.initials: K
authors.lastname: Wima
authors.affiliation: Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Hanseman
authors.affiliation: Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hoehn
authors.affiliation: Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Syed A
authors.initials: SA
authors.lastname: Ahmad
authors.affiliation: Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Shimul A
authors.initials: SA
authors.lastname: Shah
authors.affiliation: Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Abbott
mesh_terms: D055011:Ablation Techniques; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012042:Registries; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult
keywords: clear cell carcinoma; fibrolamellar variant of hepatocellular carcinoma; histopathology; scirrhous carcinoma; spindle cell carcinoma