Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreatobiliary tract are considered a separate entity from intraductal papillary mucinous neoplasms (IPMNs), especially because of the distinct molecular alterations represented by PRKACA or PRKACB fusion. However, IOPNs display a spectrum of cytoarchitectural features. Typically, an IOPN is composed of arborizing papillae lined by layers of cells with oncocytic cytoplasm, prominent nucleoli, and intraepithelial lumina, while a significant subset shows atypical morphology: lack of the characteristic cytoarchitectural features such as arborizing papillae and prominent nucleoli, or mixture with nononcocytic IPMN-like components within a single lesion. To elucidate the tumorigenesis and morphologic spectrum of IOPNs, we analyzed 22 IOPNs, including those with atypical morphology for PRKACA/PRKACB fusions in each different component separately using fluorescence in situ hybridization. In total, 18 of 22 (82%) cases harbored PRKACA/PRKACB fusions, including 3 of 3 (100%) purely typical IOPNs and 15 of 19 (79%) IOPNs with atypical morphology. In the latter, PRKACA/PRKACB fusions were noted in atypical components as well as typical IOPN components. Notably, gastric-type IPMN-like components in the fusion-positive cases were usually low grade and had scattered neoplastic cells with eosinophilic cytoplasm, a morphologic feature suggestive of an early lesion of IOPN. In summary, most IOPNs with atypical morphology either lack characteristic cytoarchitectural features or exhibit a mixture with nononcocytic IPMN-like components, harbored PRKACA/PRKACB fusion as did typical IOPN components. Our observations expanded the morphologic spectrum of IOPNs. They are expected to be useful for correct diagnosis of this neoplasm.

中文翻译：

---

PRKACA/PRKACB 融合在胰胆管内嗜酸细胞乳头状肿瘤（包括形态不典型的肿瘤）中的应用：22 例扩大形态谱的分析。


胰胆管的导管内嗜酸细胞乳头状肿瘤 (IOPN) 被认为是与导管内乳头状粘液性肿瘤 (IPMN) 不同的实体，特别是因为以 PRKACA 或 PRKACB 融合为代表的独特分子改变。然而，IOPNs 显示出一系列细胞结构特征。通常，IOPN 由树枝状乳头组成，其排列有嗜酸性细胞质、突出核仁和上皮内腔的细胞层，而重要的子集显示非典型形态：缺乏特征性细胞结构特征，例如树枝状乳头和突出核仁，或与单个病变内的非嗜酸细胞 IPMN 样成分。为了阐明 IOPN 的肿瘤发生和形态谱，我们使用荧光原位杂交分别分析了 22 个 IOPN，包括每个不同成分中 PRKACA/PRKACB 融合的非典型形态的 IOPN。总共，22 例病例中的 18 例（82%）存在 PRKACA/PRKACB 融合，其中 3 例（100%）纯典型 IOPN 中的 3 例和 19 例 IOPN 中的 15 例（79%）具有非典型形态。在后者中，在非典型成分和典型 IOPN 成分中注意到 PRKACA/PRKACB 融合。值得注意的是，融合阳性病例中的胃型 IPMN 样成分通常是低级别的，并且具有散在的肿瘤细胞，细胞质呈嗜酸性，这一形态学特征提示 IOPN 的早期病变。总之，大多数具有非典型形态的 IOPN 要么缺乏特征性细胞结构特征，要么表现出与非嗜酸细胞 IPMN 样成分的混合物，与典型 IOPN 成分一样具有 PRKACA/PRKACB 融合。我们的观察扩大了 IOPN 的形态谱。预计它们将有助于正确诊断这种肿瘤。