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Purpose <p>We reviewed recent advancements in the characterization of intraductal oncocytic papillary neoplasm (IOPN) of the pancreas, with a specific focus on developments in immunohistochemical markers, molecular pathology, and pathogenic mechanisms over the past ten years (2015–2024). Through comprehensive analysis of current literature, we aimed to elucidate the evolving understanding of IOPN’s biological behavior and diagnostic features, while identifying potential areas for future research in this distinctive pancreatic neoplasm.</p> Methods <p>English-language articles on IOPN were searched from Pubmed from the first report of IOPN of the pancreas in 2015 to 2024.</p> Results <p>Significant advancements have been achieved in IOPN research. Molecular investigations discover several immunohistochemical markers which may facilitate the diagnosis of IOPN, including CD117, HepPar-1. Significantly <i>ATP1B1::PRKACA</i>, <i>DNAJB1::PRKACA</i> and <i>ATP1B1::PRKACB</i> gene fusions are identified as molecular hallmarks of IOPN. These genetic alterations are believed to activate the cAMP-PKA signaling pathway, subsequently influencing mitochondrial substrates and contributing to the development of oncocytic features. The molecular signature not only enhances diagnostic specificity but also presents potential therapeutic targets. Furthermore, IOPN exhibits a unique tumor immune microenvironment characterized by elevated PD-L1 expression and substantial inflammatory cell infiltration. The invasive component showed decrease in CD4 + T cells and increase in CD8 + T cells and macrophages suggested the existence of an active immune surveillance, which partially explained why IOPN could have a better prognosis.</p> Conclusions <p>IOPN exhibits distinct genetic alterations and a unique immune microenvironment. These features not only elucidate the mechanism underlying the relatively favorable prognosis of IOPN and IOPN-derived pancreatic cancers but also offer novel insights into immune regulation strategies for pancreatic cancer.</p>

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Deciphering pancreatobiliary intraductal oncocytic papillary neoplasms: integrative analysis of histomorphologic patterns, immunophenotypic markers, and emerging molecular biomarkers

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月6日

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  • Yingxian Qian,
  • Shengwei Mo,
  • Xiaoyan Chang

摘要

Purpose

We reviewed recent advancements in the characterization of intraductal oncocytic papillary neoplasm (IOPN) of the pancreas, with a specific focus on developments in immunohistochemical markers, molecular pathology, and pathogenic mechanisms over the past ten years (2015–2024). Through comprehensive analysis of current literature, we aimed to elucidate the evolving understanding of IOPN’s biological behavior and diagnostic features, while identifying potential areas for future research in this distinctive pancreatic neoplasm.

Methods

English-language articles on IOPN were searched from Pubmed from the first report of IOPN of the pancreas in 2015 to 2024.

Results

Significant advancements have been achieved in IOPN research. Molecular investigations discover several immunohistochemical markers which may facilitate the diagnosis of IOPN, including CD117, HepPar-1. Significantly ATP1B1::PRKACA, DNAJB1::PRKACA and ATP1B1::PRKACB gene fusions are identified as molecular hallmarks of IOPN. These genetic alterations are believed to activate the cAMP-PKA signaling pathway, subsequently influencing mitochondrial substrates and contributing to the development of oncocytic features. The molecular signature not only enhances diagnostic specificity but also presents potential therapeutic targets. Furthermore, IOPN exhibits a unique tumor immune microenvironment characterized by elevated PD-L1 expression and substantial inflammatory cell infiltration. The invasive component showed decrease in CD4 + T cells and increase in CD8 + T cells and macrophages suggested the existence of an active immune surveillance, which partially explained why IOPN could have a better prognosis.

Conclusions

IOPN exhibits distinct genetic alterations and a unique immune microenvironment. These features not only elucidate the mechanism underlying the relatively favorable prognosis of IOPN and IOPN-derived pancreatic cancers but also offer novel insights into immune regulation strategies for pancreatic cancer.