Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreatobiliary system are tumors comprising oncocytic cells, in which three types of fusion genes involving -PRKACA/-PRKACB were recently identified. IOPNs infrequently combine with other histological subtypes of pancreatic intraductal papillary mucinous neoplasms (IPMNs) and intraductal papillary neoplasms of the bile duct (IPNBs). This study aimed to confirm the sensitivity/specificity of the fusion genes for IOPNs and to examine their significance in other oncocytic lesions. An RT-PCR, followed by DNA sequencing, was undertaken to examine the fusions in 18 histologically diagnosed IOPNs, including four combined IOPNs. Moreover, in two IOPN cases, invasive carcinomatous lesions were separately examined on their fusion status. Oncocytic thyroidal (n = 10), renal (n = 10), and salivary gland (n = 3) lesions and IPMNs (n = 9)/IPNBs (n = 4) with focal oncocytic changes were examined as controls. Fluorescence in situ hybridization using PRKACA break-apart probes was conducted for the combined IOPN cases. Target sequencing of KRAS exon2/3 and GNAS exon 8/9 was performed for IOPN cases. Fusions were detected in all IOPN cases including invasive lesions/none of the control cases. The fusion event was confirmed also in non-IOPN component in one of the four combined cases. Regarding mutation events, 5.6%/0% of IOPNs were KRAS-mt/GNAS-mt, respectively, and both components of combined IOPNs were all KRAS-wt/GNAS-wt. In conclusion, our study confirmed the sensitivity and specificity of these fusions for IOPNs. Here, we analyzed the roles of these fusion genes in combined IOPNs, proposing the possibility of IOPN development via IPMNs/IPNBs. Further studies with more combined cases are warranted.

胰胆系统的导管内嗜酸细胞乳头状肿瘤 (IOPN) 是包含嗜酸细胞的肿瘤，最近发现了三种类型的融合基因，涉及-PRKACA / -PRKACB 。IOPN 很少与胰腺导管内乳头状粘液性肿瘤 (IPMN) 和胆管导管内乳头状肿瘤 (IPNB) 的其他组织学亚型合并。本研究旨在确认 IOPN 融合基因的敏感性/特异性，并检查它们在其他嗜酸细胞病变中的意义。进行 RT-PCR，然后进行 DNA 测序，以检查 18 个组织学诊断的 IOPN 中的融合，包括四个联合 IOPN。此外，在两个 IOPN 病例中，分别检查了浸润性癌性病变的融合状态。嗜酸细胞甲状腺 ( n  = 10)、肾 ( n  = 10) 和唾液腺 ( n  = 3) 病变和IPMN ( n  = 9)/IPNB ( n = 4) 作为对照检查具有局灶性嗜酸细胞变化。对合并的 IOPN 病例进行使用 PRKACA 分离探针的荧光原位杂交。对 IOPN 病例进行了KRAS外显子2/3 和GNAS外显子 8/9的目标测序。在所有 IOPN 病例中检测到融合，包括侵袭性病变/没有对照病例。在四个合并病例之一的非 IOPN 成分中也确认了融合事件。关于突变事件，IOPNs 的 5.6%/0% 分别为KRAS -mt/ GNAS -mt，组合 IOPNs 的两个组分均为KRAS -wt/ GNAS-重量。总之，我们的研究证实了这些融合对 IOPN 的敏感性和特异性。在这里，我们分析了这些融合基因在联合 IOPN 中的作用，提出了通过 IPMN/IPNB 开发 IOPN 的可能性。有必要对更多合并病例进行进一步研究。