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Clear cell clusters in the kidney: a rare finding that should not be misdiagnosed as renal cell carcinoma

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Abstract

Clear cytoplasm is a major characteristic feature of most malignant renal neoplasms. Benign clear cells in the renal parenchyma, usually histiocytes, can occasionally be found, but they are infrequently of an epithelial nature. We report histological, immunohistochemical, ultrastructural, and cytogenomic features of clear epithelial cell clusters incidentally found in four kidney specimens. Multiple microscopic clear cell clusters were present in the cortex, often in subcapsular location. They were composed of large epithelial cells with strikingly clear cytoplasm, without nuclear atypia, arranged in solid nests, and some tubules with narrow lumina. Immunohistochemically, they were positive for AE1AE3, PAX 8, EMA, kidney-specific cadherin, cytokeratin 7, E cadherin, and CD117, with focal immunoreactivity for CD10. Carbonic anhydrase IX, vimentin, and markers related to apoptosis and proliferation were negative. Ultrastructurally, the cytoplasms were enlarged and poor in organelles, showing ballooning degeneration. Array comparative genomic hybridization showed no chromosomal gains or losses. Clear cell clusters constitute a rare finding in the kidney and must be differentiated from benign lesions (ectopic adrenal tissue, osmotic tubulopathy, histiocytic clusters, renal adenomas) and renal cell carcinomas. Clear cell clusters appear to be generated from “endocrine-type” atrophic tubules whose cells are enlarged due to intracellular oedema. Immunohistochemistry shows a distal nephron phenotype with a limited expression of a proximal marker, CD10. Coexisting chronic renal disease or ischemic conditions seem to be related to the development of clear cell clusters. Pathological, ultrastructural, and cytogenomic features do not support a preneoplastic nature of this lesion, at least in the cases studied here.

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Acknowledgements

The authors acknowledge Montserrat Vieytes, Soraya Barrera, Milagros González González, Rosa Paredes Bastos, and Olga Souto for their excellent technical work.

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Authors and Affiliations

  1. Department of Pathology, Hospital Álvaro Cunqueiro, Clara Campoamor Av., 341, 36312, Vigo, Spain

    José-Antonio Ortiz-Rey, Carmen Fachal, Laura Juaneda-Magdalena, Mónica Muñoz-Martín & Pilar San Miguel-Fraile

  2. Uropathology Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain

    José-Antonio Ortiz-Rey & Pilar San Miguel-Fraile

  3. Department of Laboratory Medicine, Hospital Álvaro Cunqueiro, Vigo, Spain

    Alfredo Repáraz-Andrade

  4. Biobank of Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain

    Susana Teijeira

  5. Department of Nephrology, Hospital Álvaro Cunqueiro, Vigo, Spain

    José-María Lamas-Barreiro

  6. Department of Urology, Hospital Álvaro Cunqueiro, Vigo, Spain

    Sheila Almuster-Domínguez

  7. Department of Pathology, Hospital POVISA, Vigo, Spain

    Carolina Gómez-de María

Authors
  1. José-Antonio Ortiz-Rey
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  10. Carolina Gómez-de María
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Contributions

Study conception and design was done by José-Antonio Ortiz-Rey. Material preparation and data collection were performed by José-Antonio Ortiz-Rey, Carmen Fachal, Mónica Muñoz-Martín, Laura Juaneda-Magdalena, Alfredo Reparaz-Andrade, Susana Teijeira, José-María Lamas-Barreiro, Sheila Almuster-Domínguez, and Carolina Gómez-de-María. Cytogenomic analysis was performed by Alfredo Repáraz-Andrade and Susana Teijeira. The first draft of the manuscript was written by José-Antonio Ortiz-Rey, Carmen Fachal, José-María Lamas-Barreiro, Pilar San Miguel-Fraile, and Sheila Almuster-Domínguez. All authors reviewed and approved the final manuscript.

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Correspondence to José-Antonio Ortiz-Rey.

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This study was approved by the pertinent ethics committee for research involving humans (Comité de Ética de la Investigación de Pontevedra-Vigo-Ourense, No. 2019/314).

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Written informed consent was obtained from all of the living patients included in the study.

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Ortiz-Rey, JA., Fachal, C., Juaneda-Magdalena, L. et al. Clear cell clusters in the kidney: a rare finding that should not be misdiagnosed as renal cell carcinoma. Virchows Arch 479, 57–67 (2021). https://doi.org/10.1007/s00428-021-03018-4

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