Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors without intervening dysplasia were identified in 9 cases: biliary intraductal papillary neoplasm (IPNB; n=5) and extrahepatic cholangiocarcinoma (n=4). The 2 tumors were histologically similar in all cases. In 5 metachronous cases, the second tumor developed 2 to 13 years after the complete resection of the first tumor. In 4 synchronous cases, 2 separate neoplasms were identified in a surgical specimen. The metachronous presentation was more common in IPNB cases, whereas the synchronous development was more frequent in cholangiocarcinoma cases. The second tumors in 4 metachronous cases (4/5; 80%) and smaller lesions in all synchronous cases (4/4; 100%) were located in a lower part of the biliary. Immunophenotypes of cytokeratins and mucin core proteins were almost identical between the 2 lesions. Next-generation sequencing also confirmed that the 2 neoplasms shared gene mutations involving KRAS, GNAS, APC, BRAF, CTNNB1, SMAD4, TP53, or ARID1A in all cases. In conclusion, multiple biliary tumors without underlying chronic biliary disease are most likely due to intraductal implantation of a single neoplasm. Thick mucinous bile in IPNB and increasing use of trans-ampullary biliary interventions may contribute to this unique form of tumor extension.

中文翻译：

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胆道肿瘤的导管内植入：“多灶性”肿瘤的潜在原因。


没有潜在慢性肝胆疾病的患者很少会出现多发性胆道肿瘤。如果没有相互连接的不典型增生，这些病变被视为多灶性肿瘤。本研究旨在确定胆道中的 2 个独立肿瘤是否代表真正的多灶性独立肿瘤发生或单个肿瘤的管腔内植入。在 9 例病例中发现了两个独立的胆管肿瘤，没有介入性发育不良：胆管内乳头状肿瘤（IPNB；n=5）和肝外胆管癌（n=4）。所有病例中这两个肿瘤的组织学相似。在 5 例异时病例中，第二个肿瘤在第一个肿瘤完全切除后 2 至 13 年出现。在 4 个同时发生的病例中，在手术标本中发现了 2 个独立的肿瘤。异时性表现在 IPNB 病例中更为常见，而同步发展在胆管癌病例中更为常见。 4 例异时病例 (4/5; 80%) 中的第二个肿瘤和所有同步病例 (4/4; 100%) 中较小的病变位于胆道下部。两个病变之间的细胞角蛋白和粘蛋白核心蛋白的免疫表型几乎相同。下一代测序还证实，这两种肿瘤在所有病例中都存在涉及 KRAS、GNAS、APC、BRAF、CTNNB1、SMAD4、TP53 或 ARID1A 的共同基因突变。总之，没有潜在慢性胆道疾病的多发性胆道肿瘤很可能是由于单个肿瘤的导管内植入所致。 IPNB 中的浓稠粘液胆汁和越来越多地使用经壶腹部胆道干预措施可能导致这种独特的肿瘤扩展形式。