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Histological and molecular characterization of TFEB-rearranged renal cell carcinomas

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Abstract

The 2016 WHO Classification of Tumors of the Urinary System recognizes microphthalmia transcription factor (MiT) family translocation carcinomas as a separate entity among renal cell carcinomas. TFE3 and transcription factor EB (TFEB) are members of the MiT family for which chromosomal rearrangements have been associated with renal cell carcinoma formation. TFEB translocation renal cell carcinoma is a rare tumor harboring a t(6;11)(p21;q12) translocation. Recently, renal cell carcinomas with TFEB amplification have been identified. TFEB amplified renal cell carcinomas have to be distinguished from TFEB-translocated renal cancer, because they may demonstrate a more aggressive behavior. Herein, we present a TFEB-translocated and a TFEB-amplified carcinoma cases and describe their distinct histological, immunohistochemical, and molecular characteristics. In addition, we review conventional morphology, immunophenotype, genetic background, and clinical outcome of TFEB-rearranged RCCs in the literature, with a special emphasis on important differential diagnoses and the diagnostic approach.

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Funding

This study was supported by the Swiss National Science Foundation (SNSF grant number S-87701-03-01).

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Authors and Affiliations

  1. Department of Pathology and Molecular Pathology, University Hospital and University Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland

    Nicolas Wyvekens, Markus Rechsteiner, Christine Fritz, Ulrich Wagner & Holger Moch

  2. Department of Oncology, University Children’s Hospital Zurich, Zurich, Switzerland

    Joëlle Tchinda

  3. Department of Pathology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Carina Wenzel & Friederike Kuithan

  4. Institute of Pathology, University Hospital Leipzig, Leipzig, Germany

    Lars-Christian Horn

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  1. Nicolas Wyvekens
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Contributions

N. W. and H. M. conceived and designed the study; provided histological descriptions of tumors; reviewed the literature; and wrote, edited, and reviewed the manuscript. C. W., F. K., and L.-C. H. provided FFPE tumor samples, clinical information, and macroscopic descriptions of tumors. M. R. and C. F. performed RNA sequencing. U. W. analyzed RNA sequencing data. J. T. performed the aCGH experiment and analyzed aCGH data. All authors critically read the manuscript, gave final approval for publication, and took full responsibility for the work as a whole.

Corresponding author

Correspondence to Holger Moch.

Ethics declarations

This study was approved by the ethics commission of the Canton Zurich. Formalin-fixed paraffin-embedded (FFPE) samples of both tumors were sent to the University Hospital Zurich as consult cases.

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The authors declare that they have no conflict of interest.

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Supplementary Table 1

Clinicopathological characteristics of t(6;11) renal cell carcinomas in the literature [4, 8,9,10,11,12, 15, 16, 21, 24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45]. F female; M male; NA not available; NED no evidence of disease; + diffuse or focal staining; − no staining; * one of these three cases positive for HMB45; ** five of the six cases positive for HMB45 or MelanA. (XLSX 17 kb)

Supplementary Table 2

Clinicopathological characteristics of TFEB amplified renal cell carcinomas in the literature [15,16,17, 19,20,21, 44, 46]. F female; M male; NA not available; NED no evidence of disease; + diffuse or focal staining; − no staining. (XLSX 15 kb)

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Wyvekens, N., Rechsteiner, M., Fritz, C. et al. Histological and molecular characterization of TFEB-rearranged renal cell carcinomas. Virchows Arch 474, 625–631 (2019). https://doi.org/10.1007/s00428-019-02526-8

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