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。


多发性胆道肿瘤很少发生在没有潜在慢性肝胆疾病的患者中。如果没有互连性发育不良，这些病变被视为多灶性肿瘤。本研究旨在确定胆道中 2 个独立的肿瘤是否代表真正的多灶性独立肿瘤发生或单个肿瘤的腔内植入。在 9 例病例中发现了 2 个独立的胆道肿瘤，无干预性异型增生： 胆道导管内状肿瘤 （IPNB;n=5） 和肝外胆管癌 （n=4）。2 个肿瘤的组织学相似。在 5 例异时性病例中，第二个肿瘤在第一个肿瘤完全切除后 2 至 13 年出现。在 4 例同步病例中，在手术标本中发现了 2 个独立的肿瘤。异时性表现在 IPNB 病例中更常见，而同步发展在胆管癌病例中更常见。4 例异时性病例的第二肿瘤 （4/5;80%） 和所有同步病例的较小病灶 （4/4;100%） 位于胆道下部。细胞角蛋白和粘蛋白核心蛋白的免疫表型在 2 个病灶之间几乎相同。下一代测序还证实，2 个肿瘤在所有病例中都共享涉及 KRAS 、 GNAS 、 APC、BRAF 、 CTNNB1 、 SMAD4 、 TP53 或 ARID1A 的基因突变。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 中粘稠的粘液胆汁和经壶腹胆道干预的增加使用可能有助于这种独特形式的肿瘤扩展。