Intraductal papillary neoplasm of the bile duct (IPNB) is a grossly visible papillary biliary neoplasm with morphological variations and occasional invasion. Recently a new classification of IPNB into type 1 and type 2 was proposed in which the type 1 IPNBs consist of fine papillary neoplastic glands and the type 2 IPNBs consist of complex branching glands, seldom with foci of solid-tubular components. However, clinicopathological and molecular characteristics of these types of IPNBs are yet to be identified. We aimed to uncover clinicopathological and molecular characteristics of the types of IPNBs. Thirty-six IPNBs were studied retrospectively. Clinicopathological features as well as molecular alterations of 31 genes were evaluated by means of targeted next-generation sequencing and immunohistochemical examination of expression of mucin and cancer-associated molecules. The 36 IPNBs were classified into 22 of type 1 and 14 of type 2. The type 1 IPNBs were associated with a non-invasive phenotype, intestinal and oncocytic subtypes, development in the intrahepatic bile duct, overt mucin production, and a relatively good prognosis. The type 2 IPNBs were associated with an invasive phenotype, the pancreatobiliary subtype, development within the extrahepatic bile duct, and worse prognosis compared with the type 1 IPNBs. In the molecular analysis, recurrent mutations were found in TP53 (34.3%), KRAS (31.4%), STK11 (25.7%), CTNNB1 (17.1%), APC (14.3%), SMAD4 (14.3%), GNAS (11.4%), PBRM1 (11.4%), ELF3 (8.6%), KMT2C (8.6%), NF1 (8.6%), PIK3CA (8.6%), ARID1A (5.7%), ARID2 (5.7%), BAP1 (5.7%), BRAF (5.7%), EPHA6 (5.7%), ERBB2 (5.7%), ERBB3 (5.7%), KMT2D (5.7%), and RNF43 (5.7%). Mutations in KRAS and GNAS were enriched in the type 1 IPNBs, whereas mutations in TP53, SMAD4, and KMT2C were enriched in the type 2 IPNBs. These results indicate that IPNBs consist of two distinct types of neoplasms specifically associated with clinicopathological features and molecular phenotypes. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

中文翻译：

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胆管内导管内乳头状肿瘤由两种不同的类型组成，这些类型与临床病理特征和分子表型特别相关。

导管内乳头状乳头状瘤（IPNB）是一种肉眼可见的乳头状胆道肿瘤，其形态学变异和偶发性浸润。最近，提出了一种新的IPNB分类，将IPNB分为1型和2型，其中1型IPNB由细小的乳头状赘生性腺组成，而2型IPNB由复杂的分支腺组成，很少有实体管状成分。但是，这些类型的IPNB的临床病理和分子特征尚未确定。我们旨在揭示IPNB类型的临床病理和分子特征。回顾性研究了36个IPNB。通过靶向下一代测序和黏蛋白和癌症相关分子表达的免疫组织化学检查，评估了31个基因的临床病理特征以及分子改变。将36个IPNB分为1型的22个和2型的14个。1型IPNB与无创表型，肠道和溶细胞亚型，肝内胆管发育，明显的粘蛋白产生以及相对较好的预后相关。 。与1型IPNB相比，2型IPNB与侵袭性表型，胰胆管亚型，肝外胆管内发育以及预后较差有关。在分子分析中，在TP53（34.3％），KRAS（31.4％），STK11（25.7％），CTNNB1（17.1％），APC（14.3％），SMAD4（14.3％），GNAS（11.4％）中发现了反复突变），PBRM1（11.4％），ELF3（8.6％），KMT2C（8.6％），NF1（8.6％），PIK3CA（8.6％），ARID1A（5.7％），ARID2（5.7％），BAP1（5.7％），BRAF（5.7％），EPHA6（ 5.7％），ERBB2（5.7％），ERBB3（5.7％），KMT2D（5.7％）和RNF43（5.7％）。KRAS和GNAS中的突变富含1型IPNB，而TP53，SMAD4和KMT2C中的突变富含2型IPNB。这些结果表明，IPNBs由与临床病理特征和分子表型特别相关的两种不同类型的肿瘤组成。©2020英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版 SMAD4和KMT2C富含2型IPNB。这些结果表明，IPNBs由与临床病理特征和分子表型特别相关的两种不同类型的肿瘤组成。©2020英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版 SMAD4和KMT2C富含2型IPNB。这些结果表明，IPNBs由与临床病理特征和分子表型特别相关的两种不同类型的肿瘤组成。©2020英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版