Intraoperative indeterminate frozen-section margin leading to an unintended R1 resection in perihilar...

Intraoperative frozen-section (FS) margin assessment is essential for guiding precise resection in perihilar cholangiocarcinoma (pCCA). However, freezing artifacts, superficial sampling, drainage-related reactive epithelial changes, and subtle cytologic atypia in well-differentiated adenocarcinoma can make intraoperative interpretation difficult. We report a 70-year-old woman with Bismuth-Corlette type II pCCA who underwent radical extrahepatic bile duct resection after PTBD-mediated biliary decompression. Intraoperative FS of the distal bile duct margin showed atypical glands of undetermined nature, while proximal margins were negative. Because additional caudal resection would probably have required combined pancreaticoduodenectomy in an elderly patient recovering from severe obstructive jaundice, the surgical team avoided extended resection after real-time surgical-pathological discussion. Permanent sections and immunohistochemistry subsequently confirmed well-differentiated adenocarcinoma involving the distal margin, perineural invasion, and regional lymph-node metastasis, consistent with an unintended R1 resection. This case illustrates that an indeterminate FS margin should be regarded as a high-risk gray-zone finding rather than a safe negative result. We propose a three-tier margin risk-stratification framework in which a "presumed positive" principle triggers repeat oriented sampling, intraoperative multidisciplinary consultation, and individualized balancing of oncologic radicality against physiological reserve. When aggressive resection is contraindicated, meticulous documentation, early adjuvant therapy, and rigorous long-term surveillance are essential.