Incidence trends and misclassification patterns of hepatocholangiocarcinoma: A SEER database analysis.

603 Background: Hepatocholangiocarcinoma (H-ChC), or combined hepatocellular–cholangiocarcinoma, is a rare primary liver malignancy with mixed hepatocytic and cholangiocytic features. True incidence remains uncertain due to misclassification as hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC). Understanding coding patterns is critical for accurate epidemiology and outcomes research. Methods: We queried the SEER 18 Registries (2000–2020) using ICD-O-3 histology codes for H-ChC (8180/3), HCC (8170–8175), and ICC (8160). Incidence rates were age-adjusted per 100,000 population. Temporal trends were assessed using Joinpoint regression. Survival outcomes were compared across groups using Kaplan–Meier and multivariable Cox regression. Misclassification was inferred by examining cases initially registered as HCC or ICC but recoded to H-ChC, and by assessing histology versus primary site discordance. Results: A total of 3,248 patients were coded as H-ChC, representing 0.8% of primary liver cancers. The age-adjusted incidence of H-ChC rose from 0.03/100,000 in 2000 to 0.07/100,000 in 2020 (annual percent change +2.1%, p<0.01), with higher incidence in males and Asian/Pacific Islander populations. Eighteen percent of H-ChC cases demonstrated discordant coding patterns, most often initially classified as HCC (62%) or ICC (31%) before being reassigned. Patients with misclassified H-ChC were younger (median age 58 vs. 62 years, p<0.01) and more likely to be non-White. Median overall survival (OS) was 16.2 months for H-ChC, intermediate between HCC (20.8 months) and ICC (13.5 months). One-year survival was 61% for HCC, 51% for H-ChC, and 44% for ICC; three-year survival was 32%, 22%, and 18%, respectively (p<0.001). On multivariable analysis, H-ChC was associated with a 22% higher mortality risk compared with HCC (HR 1.22, 95% CI 1.14–1.31) but lower than ICC (HR 0.84 95% CI 0.77–0.91). Importantly, patients misclassified as HCC or ICC had outcomes closely aligned with correctly coded H-ChC, suggesting prior survival estimates for HCC and ICC may be confounded by inclusion of H-ChC cases. Conclusions: Hepatocholangiocarcinoma is underrecognized and frequently misclassified, leading to distorted incidence and outcome estimates in population studies. Outcomes are consistently intermediate between HCC and ICC, and disparities in coding were observed by age and race. Accurate histology coding is essential to better define the burden of H-ChC and optimize management strategies.