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Introduction <p>A diagnosis of multiple primary liver tumors is extremely rare. Preoperative diagnosis based on imaging findings is difficult. Moreover, the clinical benefits of treatment strategies for multiple liver cancers remain unclear. Here, we report a case of three synchronous primary liver tumors with three distinct pathological types—hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC‑CCA)—in a single patient. Bioinformatics analysis supported at least two clonal origins, with cHCC‑CCA and ICC sharing a common lineage based on identical HBV integration sites.</p> Case presentation <p>A 63-year-old female with a history of hepatitis B for several years presented with three lesions in hepatic segment VIII. Multiphase magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid revealed a diagnosis of multiple lesions, namely, cHCC‑CCA, with multiple intrahepatic metastases. The AFP level was normal, while the CA 19 − 9 level was mildly elevated (normal range ≤ 30.00 U/ml). Hepatectomy was performed, and postoperative assessment confirmed that the large lesion was cHCC‑CCA. However, the small lesions close to the large lesion were HCC and ICC. Gene testing revealed distinct mutational profiles among the three tumors. Similar gene mutations were detected in cHCC‑CCA and ICC. We also found that gene fragments of hepatitis B virus-C (HBV-C) were inserted into the genomes of ICC and cHCC‑CCA rather than that of HCC. The genomic integration site of HBV-C in cHCC‑CCA and ICC was the same.</p> Conclusion <p>We report an extremely rare case of three synchronous primary liver tumors with three distinct pathological types (HCC, ICC, and cHCC‑CCA) in a single patient. Bioinformatics analysis supported at least two clonal origins, with cHCC‑CCA and ICC sharing a common lineage based on identical HBV integration sites. Hepatectomy represents a potential radical strategy for the treatment of multiple PLCs.</p>

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Triple primary synchronous liver cancer in one patient: the first case report and origin speculation through bioinformatics

  • 期刊论文

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  • 发表日期：

    2026年6月23日

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  • Zheng Zhou,
  • Shuai Hu,
  • Ting Liu,
  • Danling He,
  • Ting Bu,
  • Lingqiu Mao,
  • Xiyan Zheng,
  • Maoyun Xie,
  • Xianjie Shi

摘要

Introduction

A diagnosis of multiple primary liver tumors is extremely rare. Preoperative diagnosis based on imaging findings is difficult. Moreover, the clinical benefits of treatment strategies for multiple liver cancers remain unclear. Here, we report a case of three synchronous primary liver tumors with three distinct pathological types—hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC‑CCA)—in a single patient. Bioinformatics analysis supported at least two clonal origins, with cHCC‑CCA and ICC sharing a common lineage based on identical HBV integration sites.

Case presentation

A 63-year-old female with a history of hepatitis B for several years presented with three lesions in hepatic segment VIII. Multiphase magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid revealed a diagnosis of multiple lesions, namely, cHCC‑CCA, with multiple intrahepatic metastases. The AFP level was normal, while the CA 19 − 9 level was mildly elevated (normal range ≤ 30.00 U/ml). Hepatectomy was performed, and postoperative assessment confirmed that the large lesion was cHCC‑CCA. However, the small lesions close to the large lesion were HCC and ICC. Gene testing revealed distinct mutational profiles among the three tumors. Similar gene mutations were detected in cHCC‑CCA and ICC. We also found that gene fragments of hepatitis B virus-C (HBV-C) were inserted into the genomes of ICC and cHCC‑CCA rather than that of HCC. The genomic integration site of HBV-C in cHCC‑CCA and ICC was the same.

Conclusion

We report an extremely rare case of three synchronous primary liver tumors with three distinct pathological types (HCC, ICC, and cHCC‑CCA) in a single patient. Bioinformatics analysis supported at least two clonal origins, with cHCC‑CCA and ICC sharing a common lineage based on identical HBV integration sites. Hepatectomy represents a potential radical strategy for the treatment of multiple PLCs.