Deciphering the significance of tumor necrosis and developing a grading system in combined hepatocellular-cholangiocarcinoma: A multicenter pathological study.

BACKGROUND

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) lacks standardized pathological diagnostic paradigm. The significance of tumor necrosis in cHCC-CCA remains undefined. This study aimed to decipher its role and develop a practical grading system.

METHODS

A multicenter analysis was conducted on 307 cHCC-CCA patients. Tumor necrosis was pathologically graded as: TN1 (no necrosis, N = 35), TN2 (focal necrosis; maximum diameter of a single focus ≤0.55 cm/one low-power field, N = 129), and TN3 (extensive necrosis; >0.55 cm, N = 143). Associations between tumor necrosis and clinicopathological features, recurrence-free survival (RFS), overall survival (OS), early RFS (≤2 years), and late RFS (>2 years) were assessed. The impact of postoperative adjuvant transarterial chemoembolization (PA-TACE) was also evaluated.

RESULTS

Higher necrosis grades (TN2/TN3) were significantly associated with aggressive tumor characteristics, including larger tumor size, vascular invasion, and lymph node metastasis. TN3 patients had the worst median RFS (0.28 years) and OS (1.36 years), compared to TN2 (RFS: 0.68 years; OS: 2.64 years) and TN1 (RFS: 1.46 years; OS: not reached). The grading system was an independent prognostic factor for RFS, OS, and early RFS in multivariate analysis. PA-TACE significantly improved early RFS in the TN2/TN3 groups and RFS in the TN3 group specifically, but not in the TN1 group.

CONCLUSIONS

Tumor necrosis in cHCC-CCA indicates aggressive tumor biology and poorer outcomes. The proposed three-tier grading system provides robust prognostic stratification. PA-TACE benefits patients with significant necrosis (TN2/TN3), particularly in preventing early recurrence. Standardized assessment of tumor necrosis is recommended to optimize risk stratification and guide adjuvant therapy decisions for cHCC-CCA patients.