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.

Keywords: clear cell carcinoma; fibrolamellar variant of hepatocellular carcinoma; histopathology; scirrhous carcinoma; spindle cell carcinoma.