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Pediatric Renal Carcinoma Associated With Xp11.2 Translocations/TFE3 Gene Fusions and Clinicopathologic Associations

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Pediatric and Developmental Pathology

Abstract

Renal cell carcinomas (RCCs) are rare in children and studies of their subtypes and clinicopathologic associations are limited to small series. We identified 8 patients with RCC treated at our institution between 1981 and 2003, reviewed their clinicopathologic features, cytogenetics findings, and evaluated the status of TFE3 expression by immunohistochemistry and numerical chromosomal alterations by interphase fluorescent in situ hybridization on paraffin-embedded tissue. These 8 patients (5 female and 3 male) had diploidy, and 5 had morphologic features compatible with the recently described RCC associated with Xp11.2 translocations/TFE3 gene fusions and demonstrated nuclear labeling for TFE3 protein by immunohistochemistry. The translocation was confirmed in 2 of these 5 patients by conventional cytogenetics. One case was a high-grade nonpapillary RCC and the other was compatible with type 2 papillary RCC. Four patients showed at least 1 chromosomal gain including trisomy 7 and/or trisomy 17. None of the tumors from male patients showed evidence of loss of the Y chromosome, but 2 patients showed numerical abnormalities of X chromosome +add(X). Two patients had sickle cell disease, and 1 of these also had stage IV-S neuroblastoma. This study suggests that many cases of RCC in children reported under the terms “papillary” and “clear cell” likely represent Xp11.2 translocation/TFE3 gene fusion-associated RCC. It also emphasizes the unusual associations of RCC with neuroblastoma and sickle cell hemoglobinopathy, which need further study.

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References

  1. JC Barrantes KR Muir CE Toyn SE Parkes AH Cameron HB Marsden F Raafat JR Mann (1993) ArticleTitleThirty-year population-based review of childhood renal tumours with an assessment of prognostic features including tumour DNA characteristics Med Pediatr Oncol 21 24–30 Occurrence Handle1:STN:280:DyaK3s7kvV2gtg%3D%3D Occurrence Handle8381201

    CAS  PubMed  Google Scholar 

  2. DS Hartman CJ Davis SuffixJr JE Madewell AC Friedman (1982) ArticleTitlePrimary malignant renal tumors in the second decade of life: Wilms tumor versus renal cell carcinoma J Urol 127 888–891 Occurrence Handle1:STN:280:DyaL383hslSktQ%3D%3D Occurrence Handle6283183

    CAS  PubMed  Google Scholar 

  3. LP Dehner JE Leestma EB Price (1970) ArticleTitleRenal cell carcinoma in children: a clinicopathologic study of 15 cases and review of the literature J Pediatr 76 358–368 Occurrence Handle1:STN:280:DyaE3c7gslajtg%3D%3D Occurrence Handle5413660

    CAS  PubMed  Google Scholar 

  4. EE Lack JR Cassady SE Sallan (1985) ArticleTitleRenal cell carcinoma in childhood and adolescence: a clinical and pathological study of 17 cases J Urol 133 822–828 Occurrence Handle1:STN:280:DyaL2M7osFOhsg%3D%3D Occurrence Handle3989922

    CAS  PubMed  Google Scholar 

  5. R Tello JG Blickman C Buonomo J Herrin (1998) ArticleTitleMeta analysis of the relationship between tuberous sclerosis complex and renal cell carcinoma Eur J Radiol 27 131–138 Occurrence Handle10.1016/S0720-048X(97)00037-5 Occurrence Handle1:STN:280:DyaK1czgtFSjuw%3D%3D Occurrence Handle9639138

    Article  CAS  PubMed  Google Scholar 

  6. AA Renshaw (2000) ArticleTitlePediatric renal cell carcinomas: where do they fit in the new histologic classification of renal cell carcinoma? Adv Anat Pathol 7 135–140 Occurrence Handle1:STN:280:DC%2BD3c3mslaitw%3D%3D Occurrence Handle10809218

    CAS  PubMed  Google Scholar 

  7. AM Meloni RM Dobbs JE Pontes AA Sandberg (1993) ArticleTitleTranslocation (X;1) in papillary renal cell carcinoma: a new cytogenetic subtype. Cancer Genet Cytogenet 65 1–6 Occurrence Handle10.1016/0165-4608(93)90050-V Occurrence Handle1:STN:280:DyaK3s7mtFeisA%3D%3D

    Article  CAS  Google Scholar 

  8. Y Ohjimi H Iwasaki M Ishiguro H Hara A Ohgami M Kikuchi Y Kaneko (1993) ArticleTitleDeletion (X)(p11): another case of renal adenocarcinoma with involvement of Xp11 Cancer Genet Cytogenet 70 77–78 Occurrence Handle10.1016/0165-4608(93)90136-A Occurrence Handle1:STN:280:DyaK2c%2Fjs1Omtg%3D%3D Occurrence Handle8221618

    Article  CAS  PubMed  Google Scholar 

  9. V Tonk KS Wilson CF Timmons NR Schneider GE Tomlinson (1995) ArticleTitleRenal cell carcinoma with translocation (X;1): further evidence for a cytogenetically defined subtype Cancer Genet. Cytogenet 81 72–75 Occurrence Handle10.1016/S0165-4608(94)00195-2 Occurrence Handle1:STN:280:DyaK2M3pt1artQ%3D%3D Occurrence Handle7773963

    Article  CAS  PubMed  Google Scholar 

  10. B Jong ParticleDe IM Molenaar JA Leeuw VJ Idenberg JW Oosterhuis (1986) ArticleTitleCytogenetics of a renal adenocarcinoma in a 2-year-old child Cancer Genet Cytogenet 21 165–169 Occurrence Handle10.1016/0165-4608(86)90042-7 Occurrence Handle3004698

    Article  PubMed  Google Scholar 

  11. SK Sidhar J Clark S Gill R Hamoudi AJ Crew R Gwilliam M Ross WM Linehan S Birdsall J Shipley CS Cooper (1996) ArticleTitleThe t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene Hum Mol Genet 5 1333–1338 Occurrence Handle10.1093/hmg/5.9.1333 Occurrence Handle1:CAS:528:DyaK28XlsFyisbc%3D Occurrence Handle8872474

    Article  CAS  PubMed  Google Scholar 

  12. MAJ Weterman M Wilbrink A Geurts Kessel Particlevan (1996) ArticleTitleFusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas Proc Natl Acad Sci USA 93 15294–15298 Occurrence Handle10.1073/pnas.93.26.15294 Occurrence Handle1:CAS:528:DyaK2sXnt1aq Occurrence Handle8986805

    Article  CAS  PubMed  Google Scholar 

  13. I Kardas A Denis M Babinska J Gronwald J Podolski S Zajaczek A Kram J Lubinski J Limon (1998) ArticleTitleTranslocation (X;1)(p11.2;q21.2) in a papillary renal cell carcinoma in 14-year-old girl Cancer Genet Cytogenet 101 159–161 Occurrence Handle10.1016/S0165-4608(97)00266-5 Occurrence Handle1:STN:280:DyaK1c7lsFOhtw%3D%3D Occurrence Handle9494621

    Article  CAS  PubMed  Google Scholar 

  14. C Perot J Bougaran L Boccon-Gibod S Storkel G Leverger J Akker Particlevan den JL Taillemite J Couturier (1999) ArticleTitleTwo new cases of papillary renal cell carcinoma with t(X;1)(p11;q21) in females Cancer Genet Cytogenet 110 54–56 Occurrence Handle10.1016/S0165-4608(98)00181-2 Occurrence Handle1:STN:280:DyaK1M3hsVygtA%3D%3D Occurrence Handle10198623

    Article  CAS  PubMed  Google Scholar 

  15. MA Yoshida H Ochi-Takeuchi Z Gibas AA Sandberg (1985) ArticleTitleUpdating of chromosome changes in renal cell carcinoma Proc Am Assoc Cancer 26 31a

    Google Scholar 

  16. JM Shipley S Birsdall J Clark J Crew S Gill M Linehan J Gnarra S Fischer IW Craig CS Cooper (1995) ArticleTitleMapping the X chromosome breakpoint in two papillary renal cell carcinoma cell lines with a t(X;1)(p11.2;q21.2) and the first reported female Cytogenetic Cell Genetics 71 280–284 Occurrence Handle1:CAS:528:DyaK28Xhs12lsw%3D%3D Occurrence Handle10.1159/000134127

    Article  CAS  Google Scholar 

  17. T Dijuhuizen E Berg Particlevan den M Wilbrink M Weterman A Geurts Kessel Particlevan S Storkel RP Folkers (1995) ArticleTitleDistinct Xp11.2 breakpoints in two renal cell carcinomas exhibiting X; autosome translocations Genes Chromosomes Cancer 14 43–50 Occurrence Handle8527383

    PubMed  Google Scholar 

  18. J Clark YJ Lu SK Sidhar C Parker S Gill D Smedley R Hamoudi WM Linehan J Shipley CS Cooper (1997) ArticleTitleFusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma Oncogene 15 2233–2239 Occurrence Handle10.1038/sj.onc.1201394 Occurrence Handle1:CAS:528:DyaK2sXnsFajs7w%3D Occurrence Handle9393982

    Article  CAS  PubMed  Google Scholar 

  19. P Argani CR Antonescu PB Illei MY Lui CF Timmons R Newbury VE Reuter AJ Garvin AR Perez-Atayde JA Fletcher JB Beckwith JA Bridge M Ladanyi (2001) ArticleTitlePrimary 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 159 179–192 Occurrence Handle1:CAS:528:DC%2BD3MXlslamurs%3D Occurrence Handle11438465

    CAS  PubMed  Google Scholar 

  20. GE Tomlinson PD Nisen CF Timmons NR Schneider (1991) ArticleTitleCytogenetics of a renal cell carcinoma in a 17-month-old child. Evidence for Xp11.2 as a recurring breakpoint Cancer Genet Cytogenet 57 11–17 Occurrence Handle10.1016/0165-4608(91)90184-V Occurrence Handle1:STN:280:DyaK38%2FpslSnsA%3D%3D Occurrence Handle1684532

    Article  CAS  PubMed  Google Scholar 

  21. MJ Hernandez-Marti C Orellana-Alonso L Badia-Garrabou A Verdeguer Miralles A Paradis-Alos (1995) ArticleTitleRenal adenocarcinoma in an 8-year-old child, with a t(X;17)(p11.2;q25) Cancer Genet Cytogenet 83 82–83 Occurrence Handle10.1016/0165-4608(94)00184-7 Occurrence Handle1:STN:280:DyaK2MzosV2ksg%3D%3D Occurrence Handle7656211

    Article  CAS  PubMed  Google Scholar 

  22. P Argani P Lal B Hutchinson MY Lui VE Reuter M Ladanyi (2003) ArticleTitleAberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay Am J Surg Pathol 27 750–761 Occurrence Handle10.1097/00000478-200306000-00005 Occurrence Handle12766578

    Article  PubMed  Google Scholar 

  23. American Joint Committee on Cancer Manual, 6th edition. New York: Springer-Verlag, 2002;324–325

  24. MM Kattar DJ Grignon T Wallis GP Haas WA Sakr JE Pontes DW Visscher (1997) ArticleTitleClinicopathologic and interphase cytogenetic analysis of papillary (chromophilic) renal cell carcinoma Mod Pathol 10 1143–1150 Occurrence Handle1:STN:280:DyaK1c%2Fkslamuw%3D%3D Occurrence Handle9388066

    CAS  PubMed  Google Scholar 

  25. AL Burnett JI Epstein JP Gearhart (1993) ArticleTitleSpectrum of differentiation in pediatric epithelial tumors of kidney: report of two cases Urology 42 93–98 Occurrence Handle10.1016/0090-4295(93)90351-A Occurrence Handle1:STN:280:DyaK3szhvVChsA%3D%3D Occurrence Handle8328132

    Article  CAS  PubMed  Google Scholar 

  26. JN Eble G Sauter JI Epstein IA Sesterhenn (Eds) (2004) World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs IARC Press Lyon

    Google Scholar 

  27. F Desangles P Camparo C Fouet A Houlgatte M Arborio (1999) ArticleTitleTranslocation (X;1) associated with a nonpapillary carcinoma in a young woman: a new definition for an Xp11.2 RCC subtype Cancer Genet Cytogenet 113 141–144 Occurrence Handle10.1016/S0165-4608(98)00261-1 Occurrence Handle1:STN:280:DyaK1MvhsVKgtA%3D%3D Occurrence Handle10484980

    Article  CAS  PubMed  Google Scholar 

  28. H Zattara-Cannoni L Daniel P Roll C Coulange A Vagner-Capodano (2000) ArticleTitleMolecular cytogenetics of t(X;1)(p11.2;q21) with complex rearrangements in a renal cell carcinoma Cancer Genet Cytogenet 123 61–64 Occurrence Handle10.1016/S0165-4608(00)00299-5 Occurrence Handle1:CAS:528:DC%2BD3cXovFelsro%3D Occurrence Handle11120337

    Article  CAS  PubMed  Google Scholar 

  29. E Zambrano M Reyes-Mugica (2003) ArticleTitleRenal cell carcinoma with t(X;17): singular pediatric neoplasm with specific phenotype/genotype features Pediatr Dev Pathol 6 84–87 Occurrence Handle10.1007/s10024-002-1010-0 Occurrence Handle12469236

    Article  PubMed  Google Scholar 

  30. G Kovacs (1993) ArticleTitleMolecular cytogenetics of renal cell tumors Adv Cancer Res 62 89–124 Occurrence Handle1:CAS:528:DyaK2cXksl2mu7s%3D Occurrence Handle8109322 Occurrence Handle10.1016/S0065-230X(08)60316-4

    Article  CAS  PubMed  Google Scholar 

  31. BR Raney N Palmer WW Sutow E Baum A Ayala (1983) ArticleTitleRenal cell carcinoma in children Med Pediatr Oncol 11 91–98 Occurrence Handle6835176

    PubMed  Google Scholar 

  32. MA Moyad (2001) ArticleTitleReview of potential risk factors for kidney (renal cell) cancer Semin Urol Oncol 19 280–293 Occurrence Handle1:STN:280:DC%2BD38%2Fkt1Ojsg%3D%3D Occurrence Handle11769880

    CAS  PubMed  Google Scholar 

  33. LJ Medeiros G Palmedo HR Krigman G Kovacs JB Beckwith (1999) ArticleTitleOncocytoid renal cell carcinoma after neuroblastoma: a report of four cases of a distinct clinicopathologic entity Am J Surg Pathol 23 772–780 Occurrence Handle10.1097/00000478-199907000-00004 Occurrence Handle1:STN:280:DyaK1MzjtVSqsQ%3D%3D Occurrence Handle10403299

    Article  CAS  PubMed  Google Scholar 

  34. MA Koyle DA Hatch PD Furness SuffixIII MA Lovell LF Odom EA Kurzrock (2001) ArticleTitleLong-term urological complications in survivors younger than 15 months of advanced stage abdominal neuroblastoma J Urol 166 1455–1458 Occurrence Handle10.1097/00005392-200110000-00069 Occurrence Handle1:STN:280:DC%2BD3MrhvVWqsg%3D%3D Occurrence Handle11547111

    Article  CAS  PubMed  Google Scholar 

  35. DS Fenton JW Taub GM Amundson NP Padiyar B Cushing (1993) ArticleTitleRenal cell carcinoma occurring in a child 2 years after chemotherapy for neuroblastoma AJR 161 165–166 Occurrence Handle1:STN:280:DyaK3s3pslCluw%3D%3D Occurrence Handle8517297

    CAS  PubMed  Google Scholar 

  36. FP Li JR Cassady N Jaffe (1975) ArticleTitleRisk of second tumors in survivors of childhood cancer Cancer 35 1230–1235 Occurrence Handle1:STN:280:DyaE2M7htVGqsA%3D%3D Occurrence Handle1116109

    CAS  PubMed  Google Scholar 

  37. JM Fleitz SL Wootton-Gorges J Wyatt-Ashmead L McGavran M Koyle DC West EA Kurzrock KW Martin LF Odom (2003) ArticleTitleRenal cell carcinoma in long-term survivors of advanced stage neuroblastoma in early childhood Pediatr Radiol 33 540–545 Occurrence Handle10.1007/s00247-003-0913-x Occurrence Handle12748834

    Article  PubMed  Google Scholar 

  38. HR Krigman RC Bentley DK Strickland CR Miller LP Dehner K Washington (1995) ArticleTitleAnaplastic renal cell carcinoma following neuroblastoma Med Pediatr Oncol 25 52–59 Occurrence Handle1:STN:280:DyaK2M3nt1GjsQ%3D%3D Occurrence Handle7753003

    CAS  PubMed  Google Scholar 

  39. K Kato R Ijiri Y Tanaka H Kigasawa Y Toyoda Y Senga (1999) ArticleTitleMetachronous renal cell carcinoma in a child cured of neuroblastoma Med Pediatr Oncol 33 432–433 Occurrence Handle10.1002/(SICI)1096-911X(199910)33:4<432::AID-MPO24>3.0.CO;2-K Occurrence Handle1:STN:280:DyaK1MvitlOnsQ%3D%3D Occurrence Handle10491563

    Article  CAS  PubMed  Google Scholar 

  40. LF Donnelly IO Rencken K Shardell KK Matthay CR Miller RK Vartanian CA Gooding (1996) ArticleTitleRenal cell carcinoma after therapy for neuroblastoma AJR 167 915–917 Occurrence Handle1:STN:280:DyaK28vhs1GrtQ%3D%3D Occurrence Handle8819382

    CAS  PubMed  Google Scholar 

  41. RS Fairchild JL Kyner A Hermreck RN Schimke (1979) ArticleTitleNeuroblastoma, pheochromocytoma and renal cell carcinoma. Occurrence in a single patient JAMA 242 2210– 2211 Occurrence Handle10.1001/jama.242.20.2210 Occurrence Handle1:STN:280:DyaL3c%2FivF2ltg%3D%3D Occurrence Handle490809

    Article  CAS  PubMed  Google Scholar 

  42. M Tefft GF Vawter A Mitus (1968) ArticleTitleSecond primary neoplasms in children AJR Radium Ther Nucl Med 103 800–822 Occurrence Handle1:STN:280:DyaF1cvhtFylsg%3D%3D

    CAS  Google Scholar 

  43. NJ Vogelzang X Yang S Goldman S Vijayakumar G Steinberg (1998) ArticleTitleRadiation induced renal cell cancer: a report of 4 cases and review of the literature J Urol 160 1987–1990 Occurrence Handle10.1097/00005392-199812010-00011 Occurrence Handle1:STN:280:DyaK1M%2Fjt1aiug%3D%3D Occurrence Handle9817306

    Article  CAS  PubMed  Google Scholar 

  44. S Manion A Hayani A Husain R Rink D Hatch (1997) ArticleTitlePartial nephrectomy for pediatric renal cell carcinoma: an unusual case presentation Urology 49 465–468 Occurrence Handle10.1016/S0090-4295(96)00498-0 Occurrence Handle1:STN:280:DyaK2s3isFynuw%3D%3D Occurrence Handle9123719

    Article  CAS  PubMed  Google Scholar 

  45. H Dimashkieh J Choe G Mutema (2003) ArticleTitleRenal medullary carcinoma: a report of 2 cases and review of the literature Arch Pathol Lab Med 127 135–138

    Google Scholar 

  46. CJ Davis SuffixJr FK Mostofi IA Sesterhenn (1995) ArticleTitleRenal medullary carcinoma. The seventh sickle cell nephropathy Am J Surg Pathol 19 1–11 Occurrence Handle7528470 Occurrence Handle10.1097/00000478-199501000-00001

    Article  PubMed  Google Scholar 

  47. D Bruno DR Wigfall SA Zimmerman PM Rosoff JS Wiener (2001) ArticleTitleGenitourinary complications of sickle cell disease J Urol 166 803–811 Occurrence Handle10.1097/00005392-200109000-00003 Occurrence Handle1:STN:280:DC%2BD3MvksVSitw%3D%3D Occurrence Handle11490223

    Article  CAS  PubMed  Google Scholar 

  48. T Kawanami LW Young BP Wood (1988) ArticleTitleRadiological case of the month. Renal cell carcinoma in a child with hemoglobin SA disease Am. J Dis Child 142 783–784 Occurrence Handle1:STN:280:DyaL1c3ltVWrtg%3D%3D Occurrence Handle3381785

    CAS  PubMed  Google Scholar 

  49. OW Tawfik LA Moral WP Richardson KR Lee (1993) ArticleTitleMulticentric bilateral renal cell carcinomas and a vascular leiomyoma in a child Pediatr Pathol 13 289–298 Occurrence Handle1:STN:280:DyaK3s3ps1SgsA%3D%3D Occurrence Handle8516223

    CAS  PubMed  Google Scholar 

  50. BW Baron R Mick JM Baron (1994) ArticleTitleHematuria in sickle cell anemia not always benign: evidence for excess frequency of sickle cell anemia in African Americans with renal cell carcinoma Acta Haematol 92 119–122 Occurrence Handle1:STN:280:DyaK2M7ns1Oksg%3D%3D Occurrence Handle7871949 Occurrence Handle10.1159/000204199

    Article  CAS  PubMed  Google Scholar 

  51. P Argani CR Antonescu J Couturier JC Fournet R Sciot M Debiec-Rychter B Hutchinson VE Reuter L Boccon-Gibod C Timmons N Hafez M Ladanyi (2002) ArticleTitlePRCC-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 26 1553–1566 Occurrence Handle10.1097/00000478-200212000-00003 Occurrence Handle12459622

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Children’s Hospital of Michigan and Wayne State University, Detroit, MI, USA

    G. Altinok, J. Poulik & R. Rabah

  2. Department of Pathology, Harper University Hospital and Wayne State University, and Karmanos Cancer Institute, Detroit, MI, USA

    M.M. Kattar & D. Grignon

  3. Department of Cytogenetics, Wayne State University, Detroit, MI, USA

    A. Mohamed

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  1. G. Altinok
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  2. M.M. Kattar
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  3. A. Mohamed
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  4. J. Poulik
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  5. D. Grignon
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  6. R. Rabah
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Correspondence to R. Rabah.

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Altinok, G., Kattar, M., Mohamed, A. et al. Pediatric Renal Carcinoma Associated With Xp11.2 Translocations/TFE3 Gene Fusions and Clinicopathologic Associations. Pediatr Dev Pathol 8, 168–180 (2005). https://doi.org/10.1007/s10024-004-9106-3

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