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Immunophenotypic analysis of angiomyolipoma with epithelial cysts, comparison to mixed epithelial and stromal tumors and epithelial and stromal elements of normal kidney and ovaries

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Abstract

Angiomyolipoma with epithelial cysts (AMLEC) is a rare variant of renal angiomyolipoma (AML). It is characterized by a conventional AML component admixed with epithelial cysts within an “ovarian-like” stroma. Mixed epithelial and stromal tumor (MEST) is another renal neoplasm featuring epithelial cysts and “ovarian-like” stroma. While there is consensus that in MEST the epithelial and stromal components are neoplastic, in AMLEC it has been hypothesized that the epithelial component may represent renal tubular entrapment or ovarian-like transdifferentiation of tumor cells. The aim of this study was to compare the immunophenotypes of the epithelial-stromal components of AMLEC and MEST, with normal kidney and ovary to provide additional insights into the pathogenesis and relationships of these entities. In this study, we analyzed eight cases of AMLEC and 14 cases of MEST from 2003 to 2023. We used tissue microarrays, full sections, or unstained slides with an immunohistochemical panel including renal and ovarian markers: SF1, ER, PR, AR, PAX8, WT1, GATA3, CA-IX, p16, inhibin A, and BCL2. We compared these cases with ten non-neoplastic ovary and kidney samples. Our findings indicate that the epithelial component of AMLEC and MEST resembles hormone receptor positive renal tubular epithelium (AR + /ER − /PR −). AMLEC’s stromal component resembled hormone receptor positive renal stroma, while MEST’s resembled ovarian stroma, supporting mullerian transdifferentiation. Our study showed that the epithelial and stromal components of AMLEC and MEST are immunophenotypically different and also differ from normal tissues. Our findings suggest that in AMLEC, the epithelial-stromal component represents a hormonally driven proliferation of non-neoplastic renal elements within a dysregulated tumor microenvironment.

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Data availability

The data generated in this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Jamunabai Prakash, M.S., H.T. in the Research Immunohistochemistry Core for performing all the immunohistochemical stains.

Funding

The Department of Pathology and Laboratory Medicine of Indiana University School of Medicine, Indianapolis, IN, provided support for this work.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W 11Th St, Indianapolis, IN, 46202, USA

    Irem Kilic, Sheila Segura, Thomas M. Ulbright & Hector Mesa

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  1. Irem Kilic
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  2. Sheila Segura
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  3. Thomas M. Ulbright
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  4. Hector Mesa
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Contributions

Concept, design, and coordination: IK, SS, HM. Compilation and analysis of clinicopathologic and clinical data: IK, HM. Article draft, table, and figures: IK, HM. Cases and/or intellectual contributions (including article editing): all authors.

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Correspondence to Hector Mesa.

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Kilic, I., Segura, S., Ulbright, T.M. et al. Immunophenotypic analysis of angiomyolipoma with epithelial cysts, comparison to mixed epithelial and stromal tumors and epithelial and stromal elements of normal kidney and ovaries. Virchows Arch (2024). https://doi.org/10.1007/s00428-024-03827-3

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  • DOI: https://doi.org/10.1007/s00428-024-03827-3

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