Skip to main content
SpringerLink
Log in

Translocation Renal Cell Carcinomas

  • Chapter
  • First Online:
Rare Genitourinary Tumors

  • 527 Accesses

Abstract

Translocation renal cell carcinoma (tRCC) is a rare subset of kidney cancer, first added to the 2004 World Health Organization (WHO) RCC classification and recently grouped under the “MiT family tRCC.” Even though tRCC rarely presents in patients older than 40 and was only detected in around 1–2 % of renal cell cancer in adults, it is estimated to represent 15 % of RCC cases diagnosed in patients younger than 45 years. Those tumors are characterized by translocations involving the TFE3 gene located on Xp11.2 chromosome, leading to overexpression of the transcription factor E3 protein, disrupting transcription regulation. There have been at least eight partners described for TFE3 including PRCC, SFPQ, and ASPSCR1. A second, less common group is the MiT/TFEB family, t(6;11)(p21;q22), that harbors a specific TFEB translocation with at least three partners described (CLTC, Alpha, and KHDBS2). tRCCs are different from conventional RCCs, in their clinical features, epidemiology, immunohistochemistry, cytogenetic and molecular features, prognostic factors, and treatment paradigms. This chapter addresses in detail the aforementioned aspects of tRCC, to shed light on this rare type of renal cell carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cubilla A, Dillner J, Schellhammer P, et al. Tumors of the penis. World Heal Organ Classif Tumour Pathol Genet Tumour Urin Syst Male Genet Organ. 2004;65:281–298. doi:10.1016/j.urology.2004.09.048.

    Google Scholar 

  2. Argani P, Lui MY, Couturier J, Bouvier R, Fournet J-C, Ladanyi M. A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23). Oncogene. 2003;22(34):5374–8. doi:10.1038/sj.onc.1206686.

    Article  CAS  PubMed  Google Scholar 

  3. Argani P, Antonescu CR, Couturier J, et al. PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). Am J Surg Pathol. 2002;26(12):1553–66. http://www.ncbi.nlm.nih.gov/pubmed/12459622. Accessed June 21, 2015.

    Article  PubMed  Google Scholar 

  4. Argani P, Antonescu CR, Illei PB, et al. Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol. 2001;159(1):179–92. doi:10.1016/S0002-9440(10)61684-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Malouf GG, Su X, Yao H, et al. Next-generation sequencing of translocation renal cell carcinoma reveals novel RNA splicing partners and frequent mutations of chromatin-remodeling genes. Clin Cancer Res. 2014;20(15):4129–40. doi:10.1158/1078-0432.CCR-13-3036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Classe M, Malouf G, Grégoire V, Villers A, Leroy X. Is molecular analysis the key for translocation renal cell carcinoma?: an extensive study of 23 cases. 27th Eur Congr Pathol. 2015:OFP – 07. https://www1.esp-congress.org/guest/AbstractView?ABSID=10350. Accessed 24 Sept 2015.

  7. Argani P, Laé M, Hutchinson B, et al. Renal carcinomas with the t(6;11)(p21;q12): clinicopathologic features and demonstration of the specific alpha-TFEB gene fusion by immunohistochemistry, RT-PCR, and DNA PCR. Am J Surg Pathol. 2005;29(2):230–40. http://www.ncbi.nlm.nih.gov/pubmed/15644781. Accessed June 21, 2015.

    Article  PubMed  Google Scholar 

  8. Durinck S, Stawiski EW, Pavía-Jiménez A, et al. Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes. Nat Genet. 2015;47(1):13–21. doi:10.1038/ng.3146.

    Article  CAS  PubMed  Google Scholar 

  9. Argani P, Ladanyi M. Translocation carcinomas of the kidney. Clin Lab Med. 2005;25(2):363–78. doi:10.1016/j.cll.2005.01.008.

    Article  PubMed  Google Scholar 

  10. Tomlinson GE, Nisen PD, Timmons CF, Schneider NR. Cytogenetics of a renal cell carcinoma in a 17-month-old child. Evidence for Xp11.2 as a recurring breakpoint. Cancer Genet Cytogenet. 1991;57(1):11–7. http://www.ncbi.nlm.nih.gov/pubmed/1684532. Accessed June 22, 2015.

    Article  CAS  PubMed  Google Scholar 

  11. Geller JI, Ehrlich PF, Cost NG, et al. Characterization of adolescent and pediatric renal cell carcinoma: a report from the children’s oncology group study AREN03B2. Cancer. 2015;121(14):2457–64. doi:10.1002/cncr.29368.

    Article  PubMed  Google Scholar 

  12. Altinok G, Kattar MM, Mohamed A, Poulik J, Grignon D, Rabah R. Pediatric renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions and clinicopathologic associations. Pediatr Dev Pathol. 2005;8(2):168–80. doi:10.1007/s10024-004-9106-3.

    Article  CAS  PubMed  Google Scholar 

  13. Bruder E, Passera O, Harms D, et al. Morphologic and molecular characterization of renal cell carcinoma in children and young adults. Am J Surg Pathol. 2004;28(9):1117–32. http://www.ncbi.nlm.nih.gov/pubmed/15316311. Accessed June 22, 2015.

    Article  PubMed  Google Scholar 

  14. Geller JI, Argani P, Adeniran A, et al. Translocation renal cell carcinoma: lack of negative impact due to lymph node spread. Cancer. 2008;112(7):1607–16. doi:10.1002/cncr.23331.

    Article  PubMed  Google Scholar 

  15. Sukov WR, Hodge JC, Lohse CM, et al. TFE3 rearrangements in adult renal cell carcinoma. Am J Surg Pathol. 2012;36(5):1. doi:10.1097/PAS.0b013e31824dd972.

    Article  Google Scholar 

  16. Zhong M, De Angelo P, Osborne L, et al. Dual-color, break-apart FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of Xp11 translocation renal cell carcinoma and alveolar soft part sarcoma. Am J Surg Pathol. 2010;34(6):757–66. doi:10.1097/PAS.0b013e3181dd577e.

    Article  PubMed  Google Scholar 

  17. Komai Y, Fujiwara M, Fujii Y, et al. Adult Xp11 translocation renal cell carcinoma diagnosed by cytogenetics and immunohistochemistry. Clin Cancer Res. 2009;15(4):1170–6. doi:10.1158/1078-0432.CCR-08-1183.

    Article  CAS  PubMed  Google Scholar 

  18. Argani P, Olgac S, Tickoo SK, et al. Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum. Am J Surg Pathol. 2007;31(8):1149–60. doi:10.1097/PAS.0b013e318031ffff.

    Article  PubMed  Google Scholar 

  19. Argani P, Laé M, Ballard ET, et al. Translocation carcinomas of the kidney after chemotherapy in childhood. J Clin Oncol. 2006;24(10):1529–34. doi:10.1200/JCO.2005.04.4693.

    Article  CAS  PubMed  Google Scholar 

  20. Dhall D, Al-Ahmadie HA, Dhall G, Shen-Schwarz S, Tickoo SK. Pediatric renal cell carcinoma with oncocytoid features occurring in a child after chemotherapy for cardiac leiomyosarcoma. Urology. 2007;70(1):178.e13–5. doi:10.1016/j.urology.2007.03.055.

    Article  Google Scholar 

  21. Rais-Bahrami S, Drabick JJ, De Marzo AM, et al. Xp11 translocation renal cell carcinoma: delayed but massive and lethal metastases of a chemotherapy-associated secondary malignancy. Urology. 2007;70(1):178.e3–6. doi:10.1016/j.urology.2007.03.037.

    Article  Google Scholar 

  22. Schafernak KT, Yang XJ, Hsueh W, Leestma JL, Stagl J, Goldman S. Pediatric renal cell carcinoma as second malignancy: reports of two cases and a review of the literature. Can J Urol. 2007;14(6):3739–44. http://www.ncbi.nlm.nih.gov/pubmed/18163925. Accessed June 22, 2015.

    PubMed  Google Scholar 

  23. Sausville JE, Hernandez DJ, Argani P, Gearhart JP. Pediatric renal cell carcinoma. J Pediatr Urol. 2009;5(4):308–14. doi:10.1016/j.jpurol.2009.04.007.

    Article  PubMed  Google Scholar 

  24. Argani P, Hawkins A, Griffin CA, et al. A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosome translocation. Am J Pathol. 2001;158(6):2089–96. doi:10.1016/S0002-9440(10)64680-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Smith NE, Illei PB, Allaf M, et al. t(6;11) renal cell carcinoma (RCC): expanded immunohistochemical profile emphasizing novel RCC markers and report of 10 new genetically confirmed cases. Am J Surg Pathol. 2014;38(5):604–14. doi:10.1097/PAS.0000000000000203.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Argani P. MiT family translocation renal cell carcinoma. Semin Diagn Pathol. 2015;32(2):103–13. doi:10.1053/j.semdp.2015.02.003.

    Article  PubMed  Google Scholar 

  27. Meyer PN, Clark JI, Flanigan RC, Picken MM. Xp11.2 translocation renal cell carcinoma with very aggressive course in five adults. Am J Clin Pathol. 2007;128(1):70–9. doi:10.1309/LR5G1VMXPY3G0CUK.

    Article  CAS  PubMed  Google Scholar 

  28. Malouf GG, Camparo P, Molinié V, et al. Transcription factor E3 and transcription factor EB renal cell carcinomas: clinical features, biological behavior and prognostic factors. J Urol. 2011;185(1):24–9. doi:10.1016/j.juro.2010.08.092.

    Article  CAS  PubMed  Google Scholar 

  29. Salles PGO, Soto M. Kidney carcinoma associated with Xp11.2 translocation/TFE3 (ASPL-TFE3) gene fusion. Int Braz J Urol. 2005;31(3):251–4. http://www.ncbi.nlm.nih.gov/pubmed/15992428. Accessed June 24, 2015.

    Article  PubMed  Google Scholar 

  30. Mansouri D, Dimet S, Couanet D, et al. Renal cell carcinoma with an Xp11.2 translocation in a 16-year-old girl: a case report with cytological features. Diagn Cytopathol. 2006;34(11):757–60. http://www.ncbi.nlm.nih.gov/pubmed/17121199. Accessed June 24, 2015.

    Article  PubMed  Google Scholar 

  31. Schinstine M, Filie AC, Torres-Cabala C, Abati A, Linehan WM, Merino M. Fine-needle aspiration of a Xp11.2 translocation/TFE3 fusion renal cell carcinoma metastatic to the lung: report of a case and review of the literature. Diagn Cytopathol. 2006;34(11):751–6. http://www.ncbi.nlm.nih.gov/pubmed/17121198. Accessed June 24, 2015.

    Article  PubMed  Google Scholar 

  32. Weterman MJ, van Groningen JJ, Jansen A, van Kessel AG. Nuclear localization and transactivating capacities of the papillary renal cell carcinoma-associated TFE3 and PRCC (fusion) proteins. Oncogene. 2000;19(1):69–74. doi:10.1038/sj.onc.1203255.

    Article  CAS  PubMed  Google Scholar 

  33. Ellis CL, Eble JN, Subhawong AP, et al. Clinical heterogeneity of Xp11 translocation renal cell carcinoma: impact of fusion subtype, age, and stage. Mod Pathol. 2014;27(6):875–86. doi:10.1038/modpathol.2013.208.

    Article  CAS  PubMed  Google Scholar 

  34. Kuroda N, Mikami S, Pan C-C, et al. Review of renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions with focus on pathobiological aspect. Histol Histopathol. 2012;27(2):133–40. http://www.ncbi.nlm.nih.gov/pubmed/22207547. Accessed June 20, 2015.

    PubMed  Google Scholar 

  35. Suzigan S, Drut R, Faria P, et al. Xp11 translocation carcinoma of the kidney presenting with multilocular cystic renal cell carcinoma-like features. Int J Surg Pathol. 2007;15(2):199–203. doi:10.1177/1066896906295891.

    Article  PubMed  Google Scholar 

  36. Camparo P, Vasiliu V, Molinie V, et al. Renal translocation carcinomas: clinicopathologic, immunohistochemical, and gene expression profiling analysis of 31 cases with a review of the literature. Am J Surg Pathol. 2008;32(5):656–70. doi:10.1097/PAS.0b013e3181609914.

    Article  PubMed  Google Scholar 

  37. Argani P, Hicks J, De Marzo AM, et al. Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers. Am J Surg Pathol. 2010;34(9):1295–303. doi:10.1097/PAS.0b013e3181e8ce5b.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Daniel L, Lechevallier E, Giorgi R, et al. Pax-2 expression in adult renal tumors. Hum Pathol. 2001;32(3):282–7. doi:10.1053/hupa.2001.22753.

    Article  CAS  PubMed  Google Scholar 

  39. Mazal PR, Stichenwirth M, Koller A, Blach S, Haitel A, Susani M. Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study. Mod Pathol. 2005;18(4):535–40. doi:10.1038/modpathol.3800320.

    Article  CAS  PubMed  Google Scholar 

  40. Nonaka D, Chiriboga L, Soslow RA. Expression of pax8 as a useful marker in distinguishing ovarian carcinomas from mammary carcinomas. Am J Surg Pathol. 2008;32(10):1566–71. doi:10.1097/PAS.0b013e31816d71ad.

    Article  PubMed  Google Scholar 

  41. Martignoni G, Pea M, Gobbo S, et al. Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas. Mod Pathol. 2009;22(8):1016–22. doi:10.1038/modpathol.2009.58.

    Article  CAS  PubMed  Google Scholar 

  42. Argani P, Lal P, Hutchinson B, Lui MY, Reuter VE, Ladanyi M. Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am J Surg Pathol. 2003;27(6):750–61. http://www.ncbi.nlm.nih.gov/pubmed/12766578. Accessed June 26, 2015.

    Article  PubMed  Google Scholar 

  43. Klatte T, Streubel B, Wrba F, et al. Renal cell carcinoma associated with transcription factor E3 expression and Xp11.2 translocation: incidence, characteristics, and prognosis. Am J Clin Pathol. 2012;137(5):761–8. doi:10.1309/AJCPQ6LLFMC4OXGC.

    Article  PubMed  Google Scholar 

  44. Macher-Goeppinger S, Roth W, Wagener N, et al. Molecular heterogeneity of TFE3 activation in renal cell carcinomas. Mod Pathol. 2012;25(2):308–15. doi:10.1038/modpathol.2011.169.

    CAS  PubMed  Google Scholar 

  45. Malouf GG, Monzon FA, Couturier J, et al. Genomic heterogeneity of translocation renal cell carcinoma. Clin Cancer Res. 2013;19(17):4673–84. doi:10.1158/1078-0432.CCR-12-3825.

    Article  CAS  PubMed  Google Scholar 

  46. Aoki Y, Nojima M, Suzuki H, et al. Genomic vulnerability to LINE-1 hypomethylation is a potential determinant of the clinicogenetic features of multiple myeloma. Genome Med. 2012;4(12):101. doi:10.1186/gm402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hagenkord JM, Gatalica Z, Jonasch E, Monzon FA. Clinical genomics of renal epithelial tumors. Cancer Genet. 2011;204(6):285–97. doi:10.1016/j.cancergen.2011.06.001.

    Article  CAS  PubMed  Google Scholar 

  48. Alvarez K, Kash SF, Lyons-Weiler MA, et al. Reproducibility and performance of virtual karyotyping with SNP microarrays for the detection of chromosomal imbalances in formalin-fixed paraffin-embedded tissues. Diagn Mol Pathol. 2010;19(3):127–34. doi:10.1097/PDM.0b013e3181d527c5.

    Article  CAS  PubMed  Google Scholar 

  49. Stephens PJ, Greenman CD, Fu B, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011;144(1):27–40. doi:10.1016/j.cell.2010.11.055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Choueiri TK, Lim ZD, Hirsch MS, et al. Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma. Cancer. 2010;116(22):5219–25. doi:10.1002/cncr.25512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Malouf GG, Camparo P, Oudard S, et al. Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network. Ann Oncol. 2010;21(9):1834–8. doi:10.1093/annonc/mdq029.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, The University of Texas Health Science Center, University of Texas Medical School at Houston, Houston, TX, 77030, USA

    Jad Chahoud MD

  2. Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, Hopitaux de Paris, Faculty of Medicine Pierre et Marie Curie, Institut Universitaire de Cancérologie GRC5, University Paris 6, Paris, France

    Gabriel G. Malouf MD, PhD

  3. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Nizar M. Tannir MD

Authors
  1. Jad Chahoud MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriel G. Malouf MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nizar M. Tannir MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nizar M. Tannir MD .

Editor information

Editors and Affiliations

  1. Department of Oncology, Mayo Clinic, Division of Medical Oncology, Rochester, Minnesota, USA

    Lance Pagliaro

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Chahoud, J., Malouf, G.G., Tannir, N.M. (2016). Translocation Renal Cell Carcinomas. In: Pagliaro, L. (eds) Rare Genitourinary Tumors. Springer, Cham. https://doi.org/10.1007/978-3-319-30046-7_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-30046-7_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-30044-3

  • Online ISBN: 978-3-319-30046-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation