Advertisement

Kidney Cancer pp 179-192 | Cite as

Pediatric Renal Tumors: Diagnostic Updates

  • Maren Y. Fuller
Chapter

Abstract

Pediatric renal tumors are rare, and share very little overlap with adult renal tumors. By far, the most common is Wilms tumor, a triphasic tumor with an average presentation of 2–5 years of age and a very good prognosis. Unfavorable histology in Wilms tumor is a marker of adverse prognosis, and is defined by diffuse anaplasia. Congenital mesoblastic nephroma is a spindle cell tumor found almost exclusively in infants. The cellular variant has a characteristic t(12;15) ETV6–NTRK3 rearrangement. Clear cell sarcoma of the kidney has variable histology, and has been recently described to often have BCL6 corepressor (BCOR) internal tandem duplication repeats. Rhabdoid tumor has characteristic rhabdoid morphology and loss of INI1 staining by immunohistochemistry, a surrogate marker for SMARCB1 inactivation. Renal carcinomas are very rare in the pediatric population, but may be seen. These include MiT-translocation associated renal cell carcinomas; positive immunohistochemistry for TFE3 is a surrogate for the characteristic translocations. Renal medullary carcinomas are very aggressive tumors found almost exclusively in patients with sickle cell trait; INI1 loss by immunohistochemistry is characteristic. Two pediatric renal tumors are related to alterations in DICER1: cystic nephroma and anaplastic sarcoma of kidney. Ossifying renal tumor of infancy is a very rare, benign kidney tumor seen almost exclusively in infants.

Keywords

Pediatric kidney tumors Wilms tumor Mesoblastic nephroma Clear cell sarcoma of kidney Rhabdoid tumor of kidney Cystic nephroma 

References

  1. 1.
    Malkan AD, Loh A, Bahrami A, Navid F, Coleman J, Green DM, et al. An approach to renal masses in pediatrics. Pediatrics. 2015;135(1):142–58.PubMedCrossRefGoogle Scholar
  2. 2.
    Irtan S, Ehrlich PF, Pritchard-Jones K. Wilms tumor: “State-of-the-art” update, 2016. Semin Pediatr Surg. 2016;25(5):250–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Dome JS, Graf N, Geller JI, Fernandez CV, Mullen EA, Spreafico F, et al. Advances in wilms tumor treatment and biology: progress through international collaboration. J Clin Oncol. 2015;33(27):2999–3007.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Dome JS, Fernandez CV, Mullen EA, Kalapurakal JA, Geller JI, Huff V, et al. Children’s Oncology Group’s 2013 blueprint for research: renal tumors. Pediatr Blood Cancer. 2013;60(6):994–1000.PubMedCrossRefGoogle Scholar
  5. 5.
    Faria P, Beckwith JB, Mishra K, Zuppan C, Weeks D, Breslow N, et al. Focal versus diffuse anaplasia in Wilms tumor – new definitions with prognostic significance: a report from the National Wilms Tumor Study Group. Am J Surg Pathol. 1996;20(8):909–20.PubMedCrossRefGoogle Scholar
  6. 6.
    Picarsic J, Reyes-Múgica M. Phenotype and immunophenotype of the most common pediatric tumors. Appl Immunohistochem Mol Morphol. 2015;23(5):313–26.PubMedCrossRefGoogle Scholar
  7. 7.
    Gadd S, Huff V, Walz AL, Ooms AHAG, Armstrong AE, Gerhard DS, et al. A Children’s Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nat Genet. 2017;49(10):1487–94.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Treger TD, Chowdhury T, Pritchard-Jones K, Behjati S. The genetic changes of Wilms tumour. Nat Rev Nephrol. 2019;15(4):240–51.PubMedCrossRefGoogle Scholar
  9. 9.
    Knezevich SR, Garnett MJ, Pysher TJ, Beckwith JB, Grundy PE, Sorensen PHB. ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res. 1998;58(22):5046–8.PubMedGoogle Scholar
  10. 10.
    Rubin BP, Chen CJ, Morgan TW, Xiao S, Grier HE, Kozakewich HP, et al. Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma. Am J Pathol. 1998;153(5):1451–8.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Rudzinski ER, Lockwood CM, Stohr BA, Vargas SO, Sheridan R, Black JO, et al. Pan-Trk immunohistochemistry identifies NTRK rearrangements in pediatric mesenchymal tumors. Am J Surg Pathol. 2018;42(7):927–35.PubMedCrossRefGoogle Scholar
  12. 12.
    Gooskens SLM, Furtwängler R, Vujanic GM, Dome JS, Graf N, van den Heuvel-Eibrink MM. Clear cell sarcoma of the kidney: a review. Eur J Cancer. 2012;48(14):2219–26.PubMedCrossRefGoogle Scholar
  13. 13.
    Mirkovic J, Calicchio M, Fletcher CD, Perez-Atayde AR. Diffuse and strong cyclin D1 immunoreactivity in clear cell sarcoma of the kidney. Histopathology. 2015;67(3):306–12.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Ueno-Yokohata H, Okita H, Nakasato K, Akimoto S, Hata JI, Koshinaga T, et al. Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney. Nat Genet. 2015;47(8):861–3.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Kenny C, Bausenwein S, Lazaro A, Furtwängler R, Gooskens SLM, Van Den Heuvel Eibrink M, et al. Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney: not the full story. J Pathol. 2016;238(5):617–20.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Kao Y-C, Sung Y-S, Zhang L, Huang S-C, Argani P, Chung CT, et al. Recurrent BCOR internatl tandem duplication and YWHAE-NUTM2B fusions in soft tissue undifferentiated round cell sarcoma of infancy – overlapping genetic features with clear cell sarcoma of kidney. Am J Surg Pathol. 2016;40(8):1009–20.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Roy A, Kumar V, Zorman B, Fang E, Haines K, Doddapaneni H, et al. Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nat Commun. 2015;6:8891.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    O’Meara E, Stack D, Lee CH, Garvin AJ, Morris T, Argani P, et al. Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney. J Pathol. 2012;227(1):72–80.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Karlsson J, Valid A, Gisselsson D. BCOR internal tandem duplication and YWHAE-NUTM2B/E fusion are mutually exclusive events in clear cell sarcoma of the kidney. Genes Chromosomes Cancer. 2016;55:120–3.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Wong MK, Ng CCY, Kuick CH, Aw SJ, Rajasegaran V, Lim JQ, et al. Clear cell sarcomas of the kidney are characterised by BCOR gene abnormalities, including exon 15 internal tandem duplications and BCOR-CCNB3 gene fusion. Histopathology. 2018;72(2):320–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Argani P, Kao Y-C, Zhang L, Bacchi C, Matoso A, Alaggio R, et al. Primary renal sarcomas with BCOR-CCNB3 gene fusion. Am J Surg Pathol. 2017;41(12):1702–12.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms tumors: results from the First National Wilms’ Tumor Study. Cancer. 1978;41(5):1937–48.PubMedCrossRefGoogle Scholar
  23. 23.
    Bourdeaut F, Lequin D, Brugières L, Reynaud S, Dufour C, Doz F, et al. Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor. Clin Cancer Res. 2011;17(1):31–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Sigauke E, Rakheja D, Maddox DL, Hladik CL, White CL, Timmons CF, et al. Absence of expression of SMARCB1/INI1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: an immunohistochemical study with implications for diagnosis. Mod Pathol. 2006;19(5):717–25.PubMedCrossRefGoogle Scholar
  25. 25.
    Sredni ST, Tomita T. Rhabdoid tumor predisposition syndrome. Pediatr Dev Pathol. 2015;18(1):49–58.PubMedCrossRefGoogle Scholar
  26. 26.
    Geller JI, Ehrlich PF, Cost NG, Khanna G, Mullen EA, Gratias EJ, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Cajaiba MM, Dyer LM, Geller JI, Jennings LJ, George D, Kirschmann D, et al. The classification of pediatric and young adult renal cell carcinomas registered on the children’s oncology group (COG) protocol AREN03B2 after focused genetic testing. Cancer. 2018;124(16):3381–9.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Perlman EJ. Pediatric renal cell carcinoma. Surg Pathol Clin. 2010;3(3):641–51.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Davis CJ, Mostofi FK, Sesterhenn IA. Renal medullary carcinoma. The seventh sickle cell nephropathy. Am J Surg Pathol. 1995;19(1):1–11.PubMedCrossRefGoogle Scholar
  30. 30.
    Cheng JX, Tretiakova M, Gong C, Mandal S, Krausz T, Taxy JB. Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior. Mod Pathol. 2008;21(6):647–52.PubMedCrossRefGoogle Scholar
  31. 31.
    Liu Q, Galli S, Srinivasan R, Linehan WM, Tsokos M, Merino MJ. Renal medullary carcinoma: molecular, immunohistochemistry, and morphologic correlation. Am J Surg Pathol. 2013;37(3):368–74.PubMedCrossRefGoogle Scholar
  32. 32.
    Carlo MI, Chaim J, Patil S, Kemel Y, Schram AM, Woo K, et al. Genomic characterization of renal medullary carcinoma and treatment outcomes. Clin Genitourin Cancer. 2017;15(6):e987–94.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Debelenko LV, Raimondi SC, Daw N, Shivakumar BR, Huang D, Nelson M, et al. Renal cell carcinoma with novel VCL-ALK fusion: new representative of ALK-associated tumor spectrum. Mod Pathol. 2011;24(3):430–42.PubMedCrossRefGoogle Scholar
  34. 34.
    Smith N, Deyrup AT, Fletcher JA, Bridge JA, Illei PB, Netto GJ, et al. VCL-ALK renal cell carcinoma in children with sickle-cell trait: the eighth sickle-cell nephropathy? Am J Surg Pathol. 2014;38(6):858–63.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Mariño-Enríquez A, Ou W-B, Weldon CB, Fletcher JA, Pérez-Atayde AR. ALK rearrangement in sickle cell trait-associated renal medullary carcinoma. Genes Chromosom Cancer. 2011;50(3):146–53.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Cajaiba MM, Jennings LJ, Rohan SM, Perez-Atayde AR, Marino-Enriquez A, Fletcher JA, et al. ALK rearranged renal cell carcinomas in children. Genes Chromosom Cancer. 2016;55(5):442–51.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Doros LA, Rossi CT, Yang J, Field A, Williams GM, Messinger Y, et al. DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma. Mod Pathol. 2014;27(9):1267–80.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Cajaiba MM, Khanna G, Smith EA, Gellert L, Chi YY, Mullen EA, et al. Pediatric cystic nephromas: distinctive features and frequent DICER1 mutations. Hum Pathol. 2016;48:81–7.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Li Y, Pawel BR, Hill DA, Epstein JI, Argani P. Pediatric cystic nephroma is morphologically, immunohistochemically, and genetically distinct from adult cystic nephroma. Am J Surg Pathol. 2017;41(4):472–81.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Wu MK, Cotter MB, Pears J, McDermott MB, Fabian MR, Foulkes WD, et al. Tumor progression in DICER1-mutated cystic nephroma – witnessing the genesis of anaplastic sarcoma of the kidney. Hum Pathol. 2016;53:114–20.PubMedCrossRefGoogle Scholar
  41. 41.
    Vujanić GM, Kelsey A, Perlman EJ, Sandstedt B, Beckwith JB. Anaplastic sarcoma of the kidney: a clinicopathologic study of 20 cases of a new entity with polyphenotypic features. Am J Surg Pathol. 2007;31(10):1459–68.PubMedCrossRefGoogle Scholar
  42. 42.
    Sebire NJ, Vujanic GM. Paediatric renal tumours: recent developments, new entities and pathological features. Histopathology. 2009;54(5):516–28.PubMedCrossRefGoogle Scholar
  43. 43.
    Wu MK, Vujanic GM, Fahiminiya S, Watanabe N, Thorner PS, O’Sullivan MJ, et al. Anaplastic sarcomas of the kidney are characterized by DICER1 mutations. Mod Pathol. 2018;31(1):169–78.PubMedCrossRefGoogle Scholar
  44. 44.
    Chatten J, Cromie WJ, Duckett JW. Ossifying tumor of infantile kidney: report of two cases. Cancer. 1980;45(3):609–12.PubMedCrossRefGoogle Scholar
  45. 45.
    Hu J, Wu Y, Qi J, Zhang C, Lv F. Ossifying renal tumor of infancy (ORTI): a case report and review of the literature. J Pediatr Surg. 2013;48(2):e37–40.PubMedCrossRefGoogle Scholar
  46. 46.
    Guan W, Yan Y, He W, Qiao M, Liu Y, Wang Y, et al. Ossifying renal tumor of infancy (ORIT): the clinicopathological and cytogenetic feature of two cases and literature review. Pathol Res Pract. 2016;212(11):1004–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Maren Y. Fuller
    • 1
  1. 1.Texas Children’s Hospital/Baylor College of MedicineHoustonUSA

Personalised recommendations