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“High-grade oncocytic renal tumor”: morphologic, immunohistochemical, and molecular genetic study of 14 cases

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Abstract

The spectrum of the renal oncocytic tumors has been expanded in recent years to include several novel and emerging entities. We describe a cohort of novel, hitherto unrecognized and morphologically distinct high-grade oncocytic tumors (HOT), currently diagnosed as “unclassified” in the WHO classification. We identified 14 HOT by searching multiple institutional archives. Morphologic, immunohistochemical (IHC), molecular genetic, and molecular karyotyping studies were performed to investigate these tumors. The patients included 3 men and 11 women, with age range from 25 to 73 years (median 50, mean 49 years). Tumor size ranged from 1.5 to 7.0 cm in the greatest dimension (median 3, mean 3.4 cm). The tumors were all pT1 stage. Microscopically, they showed nested to solid growth, and focal tubulocystic architecture. The neoplastic cells were uniform with voluminous oncocytic cytoplasm. Prominent intracytoplasmic vacuoles were frequently seen, but no irregular (raisinoid) nuclei or perinuclear halos were present. All tumors demonstrated prominent nucleoli (WHO/ISUP grade 3 equivalent). Nine of 14 cases were positive for CD117 and cytokeratin (CK) 7 was either negative or only focally positive in of 6/14 cases. All tumors were positive for AE1-AE3, CK18, PAX 8, antimitochondrial antigen, and SDHB. Cathepsin K was positive in 13/14 cases and CD10 was positive in 12/13 cases. All cases were negative for TFE3, HMB45, Melan-A. No TFEB and TFE3 genes rearrangement was found in analyzable cases. By array CGH, complete chromosomal losses or gains were not found in any of the cases, and 3/9 cases showed absence of any abnormalities. Chromosomal losses were detected on chromosome 19 (4/9), 3 with losses of the short arm (p) and 1 with losses of both arms (p and q). Loss of chromosome 1 was found in 3/9 cases; gain of 5q was found in 1/9 cases. On molecular karyotyping, 3/3 evaluated cases showed loss of heterozygosity (LOH) on 16p11.2-11.1 and 2/3 cases showed LOH at 7q31.31. Copy number (CN) losses were found at 7q11.21 (3/3), Xp11.21 (3/3), Xp11.22-11.21 (3/3), and Xq24-25 (2/3). CN gains were found at 13q34 (2/3). Ten patients with available follow up information were alive and without disease progression, after a mean follow-up of 28 months (1 to 112 months). HOT is a tumor with unique morphology and its IHC profile appears mostly consistent. HOT should be considered as an emerging renal entity because it does not meet the diagnostic criteria for other recognized eosinophilic renal tumors, such as oncocytoma, chromophobe renal cell carcinoma (RCC), TFE3 and TFEB RCC, SDH-deficient RCC, and eosinophilic solid and cystic RCC.

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Contributions

Huiying He and Ondrej Hes: revision of all cases, evaluation of immunohistochemistry. Kiril Trpkov and Ondrej Hes: design of study. Petr Martinek: molecular genetics. Ozlem Tanas Isikci, Kristyna Pivovarcikova: evaluation of immunohistochemistry. Anthony J Gill: evaluation of SDHB mutation and SDHB staining interpretation. Cristina Maggi-Galuzzi, Reza Alaghehbandan, Maria Tretiakova, Jose Ignacio Lopez, Sean Williamson, Delia Perez Montiel, Maris Sperga, Eva Comperat, Fadi Brimo, Michael Bonert, and Ali Yilmaz: case contribution, providing follow up data, and help with discussion. Kveta Michalova, David Slouka: follow up information, photodocumentation, Kristyna Prochazkova, Milan Hora: evaluation of clinical data. Michal Michal: discussion.

Funding

The study was supported by the Charles University Research Fund (project number Q39) and by the project Institutional Research Fund of University Hospital Plzen (FN 00669806).

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Authors and Affiliations

  1. Department of Pathology, Health Science Center, Peking University, Beijing, China

    Huiying He

  2. Department of Pathology and Laboratory Medicine, Calgary Laboratory Services and University of Calgary, Calgary, AB, Canada

    Kiril Trpkov & Ali Yilmaz

  3. Department of Pathology, Medical Faculty and Charles University Hospital Plzen, Alej Svobody 80, 304 60, Pilsen, Czech Republic

    Petr Martinek, Kristyna Pivovarcikova, Kveta Michalova, Michal Michal & Ondrej Hes

  4. Department of Pathology, Ankara Education and Research Hospital, Ankara, Turkey

    Ozlem Tanas Isikci

  5. Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA

    Cristina Maggi-Galuzzi

  6. Department of Pathology, Faculty of Medicine, University of British Columbia, Royal Columbian Hospital, Vancouver, BC, Canada

    Reza Alaghehbandan

  7. Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia

    Anthony J Gill

  8. University of Sydney, Sydney, NSW, 2006, Australia

    Anthony J Gill

  9. NSW Health Pathology Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia

    Anthony J Gill

  10. Department of Anatomic Pathology, Harborview Medical Center, Seattle, WA, USA

    Maria Tretiakova

  11. BioCruces Institute, Cruces University Hospital, University of the Basque Country (UPV/EHU), Barakaldo, Bizkaia, Spain

    Jose Ignacio Lopez

  12. Department of Pathology, Henry Ford Hospital, Detroit, MI, USA

    Sean R. Williamson

  13. Department of Pathology, Instituto Nacional de Cancerologia, Mexico City, Mexico

    Delia Perez Montiel

  14. Department of Pathology, Riga Stradin’s University, Riga, Latvia

    Maris Sperga

  15. Sorbonne Université Service d’Anatomie et Cytologie Pathologiques Hôpital Tenon, HUEP, Paris, France

    Eva Comperat

  16. Department of Pathology, McGill University, Montreal, QC, Canada

    Fadi Brimo

  17. Biomedicine Center, Charles University, Medical Faculty and Charles University Hospital Plzen, Prague, Czech Republic

    David Slouka

  18. Department of Urology, Charles University, Medical Faculty and Charles University Hospital Plzen, Prague, Czech Republic

    Kristyna Prochazkova & Milan Hora

  19. Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada

    Michael Bonert

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  1. Huiying He
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  2. Kiril Trpkov
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  16. Kristyna Pivovarcikova
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  20. Milan Hora
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  21. Michael Bonert
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  22. Michal Michal
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  23. Ondrej Hes
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Correspondence to Ondrej Hes.

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Study design has been approved by local ethical committee (Charles University, Medical School Plzen) LEK FN Plzeň.

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The authors declare that they have no conflict of interest.

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He, H., Trpkov, K., Martinek, P. et al. “High-grade oncocytic renal tumor”: morphologic, immunohistochemical, and molecular genetic study of 14 cases. Virchows Arch 473, 725–738 (2018). https://doi.org/10.1007/s00428-018-2456-4

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