Background Synchronous hepatocellular carcinoma (HCC) and intraductal papillary neoplasm of the bile duct (IPNB)-associated intrahepatic cholangiocarcinoma (ICC) is a rare dual-lineage hepatobiliary malignancy. Although radical resection for conventional synchronous HCC and ICC has been well documented, reported experience with margin-negative (R0) resection for this specific tumor complex remains scarce. Case Summary A 77-year-old male with resolved hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection with sustained virological response (SVR) presented with intermittent right upper quadrant pain, abdominal distension, scleral icterus, pruritus, nausea, and vomiting. Imaging studies revealed multifocal hepatic lesions and a biliary tract mass, and he was initially misdiagnosed as metastatic cholangiocarcinoma. Staging laparoscopy confirmed resectability, followed by open margin-negative resection. Intraoperative cholangioscopy and frozen-section analysis identified a pedunculated IPNB arising from the right hepatic duct and confirmed negative bile duct margins. Final pathology confirmed well-differentiated HCC and a separate high-grade IPNB with associated moderately to poorly differentiated ICC. The HCC and biliary lesion were separated by non-neoplastic parenchyma without a transition between them, excluding combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Regional lymph nodes were not removed or histologically examined (pNx for both tumors). Margins exceeded 1 cm for both components. The patient recovered uneventfully; at 3-month follow-up, tumor markers were normal with no radiological recurrence. Conclusion This report presents a rare case of margin-negative (R0) resection with unassessed nodal status (pNx) for synchronous HCC and IPNB-associated ICC in a patient with resolved HBV infection and HCV infection with SVR. The coexistence of multifocal hepatic lesions with a biliary tract mass should not be presumed to indicate metastatic disease; in this case, surgical exploration with intraoperative frozen-section analysis and cholangioscopy was useful for diagnosis and management, with the 3-month follow-up documenting only an early postoperative outcome.
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