Rare Long-Term Transformation from Solitary Hepatocellular Carcinoma to Synchronous Double Primary Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: A Case Report and Literature Review.

Synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma (sdpHCC-ICC) is rare, particularly when evolving metachronously from solitary HCC. This study reports a unique case of such transformation over two decades and reviews the relevant literature. A 55-year-old male with chronic hepatitis B underwent curative resection for HCC in 2005. Following multiple recurrences treated with local therapies over 19 years, subsequent resection in 2024 revealed two distinct malignancies: recurrent HCC and a spatially separate intrahepatic cholangiocarcinoma (ICC), confirmed by immunohistochemistry. We additionally analyzed 31 reported sdpHCC-ICC cases to summarize their clinicopathological characteristics and outcomes. The patient eventually developed systemic metastases despite adjuvant therapy. Our review highlights the marked biological heterogeneity and diagnostic challenges associated with sdpHCC-ICC. This case suggests that prolonged tumor evolution in chronically injured livers may be associated with biological heterogeneity and phenotypic divergence. Our findings support the potential value of long-term surveillance and repeated pathological reassessment in selected long-term HCC survivors with atypical recurrence patterns.