eMedicine Specialties > Pediatrics: General Medicine > Oncology

Wilms Tumor

Author: Arnold C Paulino, MD, Associate Professor, Department of Radiology, Division of Radiation Oncology, Associate Professor of Pediatrics, Baylor College of Medicine; Consulting Staff, Methodist Hospital and Texas Children's Hospital
Coauthor(s): Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Contributor Information and Disclosures

Updated: Mar 3, 2009

Introduction

Background

Wilms tumor, or nephroblastoma, is the most common childhood abdominal malignancy. Over the past 4 decades, the multidisciplinary approach to this tumor has become an example for successful cancer treatment. At present, survival rates of children with this neoplasm are approximately 85-90%. This is in contrast to the rate 50 years ago, when only 10% of children survived. The addition of radiation therapy to surgery alone improved survival rates to approximately 40%. Since the use of chemotherapy began, survival rates of 80-90% have been observed.

The National Wilms Tumor Study Group (NWTSG) and the International Society of Pediatric Oncology (SIOP) have identified several chemotherapeutic agents through their clinical trials.  When used together, these agents lead to a cure in most children with this renal tumor. In addition, the guidelines for surgical treatment and the role of radiation therapy are better defined now than ever before.

With overall survival rates approaching 90%, therapeutic trials have focused on limiting treatment-related toxicity.1 Understanding of the molecular mechanisms that contribute to the development of Wilms tumor has also greatly increased, making Wilms tumorigenesis a model for the understanding of the development of other tumors.

Pathophysiology

In the early 1970s, Knudson and Strong proposed a genetic model for the development of Wilms tumor.2 WT1, the first Wilms tumor suppressor gene at chromosomal band 11p13, was identified as a direct result of the study of children with Wilms tumor who also had aniridia, genitourinary anomalies, and mental retardation (WAGR syndrome).3 Karyotypic analysis revealed constitutional deletions within the short arm of 1 copy of chromosome 11. The 11p13 locus was subsequently demonstrated to encompass numerous contiguous genes, including the aniridia gene PAX6 and the Wilms tumor suppressor gene WT1, which was cloned in 1990. WT1 encodes a transcription factor critical to normal renal and gonadal development.

Characterization of this novel tumor suppressor gene has provided insight into the mechanisms underlying normal kidney development and Wilms tumorigenesis. The WT1 gene is the specific target of mutations and deletions in a subset of patients with sporadic Wilms tumors, as well as in the germline of some children (eg, those with Denys-Drash syndrome) with a genetic predisposition to develop this cancer.4

A second gene that predisposes individuals to develop the Wilms tumor has been identified (but is not yet cloned) telomeric of WT1, at 11p15. This locus was proposed on the basis of studies in patients with both Wilms tumor and Beckwith-Wiedemann syndrome (BWS), another congenital Wilms-tumor predisposition syndrome linked to chromosomal band 11p15.3 BWS is an overgrowth syndrome characterized by visceromegaly, macroglossia, and hyperinsulinemic hypoglycemia. In addition, patients with BWS are predisposed to have several embryonal neoplasms including Wilms tumor. Thus far, a few candidate loci for Wilms tumor and BWS have been proposed. These loci include the insulinlike growth factor II gene (IGFII), H19 (for an untranslated RNA), and that encoding for p57kip2.

Results of linkage analyses in large pedigrees with familial transmission of susceptibility to the Wilms tumor suggest the existence of additional genetic loci.

Finally, loci at 16q, 1p, 7p, and 17p have also been implicated in the biology of Wilms tumor, although these loci do not seem to predispose individuals to develop a Wilms tumor. Instead, they seem to be associated with the phenotype or the outcome.1,5

Frequency

United States

Wilms tumor affects approximately 10 children and adolescents per 1 million before the age of 15 years. Therefore, it accounts for 6-7% of all childhood cancers in North America. As a result, about 450-500 new cases are diagnosed each year on this continent. In 5-10% of patients, both kidneys are affected at the same time (synchronous bilateral Wilms tumor) or one after the other (metachronous bilateral Wilms tumor).

International

Wilms tumor appears to be most common among blacks and least common in the East Asian population.6 The incidence in Europe is similar to that reported in North America.

Mortality/Morbidity

Before the multimodality approach was available, the survival rate of patients was less than 50%. With the current NWTSG and SIOP strategies, survival rates are approaching 90%. Most survivors of Wilms tumor have good functional outcomes and quality of life. See also Prognosis.

Race

Wilms tumor is relatively more common in blacks than in whites and is rare in East Asians. Estimates suggest 6-9 cases per million person years in whites, 3-4 cases per million person years in East Asians and more than 10 cases per million person years among black populations.6

Sex

Among patients with unilateral Wilms tumor enrolled in all NWTSG protocols, the male-to-female ratio was 0.92:1. For patients with bilateral disease, the male-to-female ratio was 0.60:1.

Age

The median age at diagnosis is approximately 3.5 years. The median age is highest for patients with unilateral unicentric disease (36.1 mo) and lowest for those with synchronous bilateral Wilms tumors (25.5 mo).6

Clinical

History

The most common manifestation of Wilms tumor is an asymptomatic abdominal mass; an abdominal mass occurs in 80% of children at presentation. Abdominal pain or hematuria occurs in 25%. Urinary tract infection and varicocele are less common findings than these. Hypertension, gross hematuria, and fever are observed in 5-30% of patients. A few patients with hemorrhage into their tumor may present with hypotension, anemia, and fever. Rare patients with advanced disease may present with respiratory symptoms related to lung metastases.

Physical

Examination often reveals a palpable abdominal mass. Pay special attention to features of those syndromes (WAGR syndrome and Beckwith-Wiedemann syndrome [BWS]) associated with Wilms tumor (ie, aniridia, genitourinary malformations, and signs of overgrowth).

The abdominal mass should be carefully examined. Palpating a mass too vigorously could lead to the rupture of a large tumor into the peritoneal cavity.

Causes

Wilms tumor is thought to be caused by alterations of genes responsible for normal genitourinary development. Examples of common congenital anomalies associated with Wilms tumor are cryptorchidism, a double collecting system, horseshoe kidney, and hypospadias. Environmental exposures, although considered, seem relatively unlikely to play a role. See Pathophysiology.

More on Wilms Tumor

Overview: Wilms Tumor
Differential Diagnoses & Workup: Wilms Tumor
Treatment & Medication: Wilms Tumor
Follow-up: Wilms Tumor
Multimedia: Wilms Tumor
References
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References

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  2. Knudson AG, Strong LC. Mutation and cancer: a model for Wilms' tumor of the kidney. J Natl Cancer Inst. Feb 1972;48(2):313-24. [Medline].

  3. Coppes MJ, Haber DA, Grundy PE. Genetic events in the development of Wilms' tumor. N Engl J Med. Sep 1 1994;331(9):586-90. [Medline].

  4. Coppes MJ, Huff V, Pelletier J. Denys-Drash syndrome: relating a clinical disorder to genetic alterations in the tumor suppressor gene WT1. J Pediatr. Nov 1993;123(5):673-8. [Medline].

  5. Grundy PE, Breslow NE, Li S, et al. Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol. Oct 10 2005;23(29):7312-21. [Medline].

  6. Breslow N, Olshan A, Beckwith JB, Green DM. Epidemiology of Wilms tumor. Med Pediatr Oncol. 1993;21(3):172-81. [Medline].

  7. van den Heuvel-Eibrink MM, Grundy P, Graf N, et al. Characteristics and survival of 750 children diagnosed with a renal tumor in the first seven months of life: A collaborative study by the SIOP/GPOH/SFOP, NWTSG, and UKCCSG Wilms tumor study groups. Pediatr Blood Cancer. Jun 2008;50(6):1130-4. [Medline].

  8. Refaie HD, Sarhan M, Hafez A. Role of CT in assessment of unresectable Wilms' tumor response after preoperative chemotherapy in pediatrics. ScientificWorldJournal. Jul 13 2008;8:661-9. [Medline].

  9. Mitchell C, Pritchard-Jones K, Shannon R, et al. Immediate nephrectomy versus preoperative chemotherapy in the management of non-metastatic Wilms' tumour: results of a randomised trial (UKW3) by the UK Children's Cancer Study Group. Eur J Cancer. Oct 2006;42(15):2554-62. [Medline].

  10. Reinhard H, Semler O, Burger D, et al. Results of the SIOP 93-01/GPOH trial and study for the treatment of patients with unilateral nonmetastatic Wilms Tumor. Klin Padiatr. May-Jun 2004;216(3):132-40. [Medline].

  11. Meisel JA, Guthrie KA, Breslow NE, Donaldson SS, Green DM. Significance and management of computed tomography detected pulmonary nodules: a report from the National Wilms Tumor Study Group. Int J Radiat Oncol Biol Phys. Jun 1 1999;44(3):579-85. [Medline].

  12. Coppes MJ, Arnold M, Beckwith JB, et al. Factors affecting the risk of contralateral Wilms tumor development: a report from the National Wilms Tumor Study Group. Cancer. Apr 1 1999;85(7):1616-25. [Medline].

  13. D'Angio GJ, Breslow N, Beckwith JB, et al. Treatment of Wilms' tumor. Results of the Third National Wilms' Tumor Study. Cancer. Jul 15 1989;64(2):349-60. [Medline].

  14. Kalapurakal JA, Li SM, Breslow NE, et al. Influence of radiation therapy delay on abdominal tumor recurrence in patients with favorable histology Wilms' tumor treated on NWTS-3 and NWTS-4: a report from the National Wilms' tumor Study Group. Int J Radiat Oncol Biol Phys. 2003;57:495-9. [Medline].

  15. Green DM, Breslow NE, Beckwith JB, et al. Treatment with nephrectomy only for small, stage I/favorable histology Wilms tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol. Sep 1/ 2001;19:3719-24. [Medline].

  16. D'Angio GJ, Rosenberg H, Sharples K, et al. Position paper: imaging methods for primary renal tumors of childhood: costs versus benefits [published erratum appears in Med Pediatr Oncol 1993;21(9):695]. Med Pediatr Oncol. 1993;21(3):205-12. [Medline].

  17. Green DM, Donckerwolcke R, Evans AE, D'Angio GJ. Late effects of treatment for Wilms tumor. Hematol Oncol Clin North Am. Dec 1995;9(6):1317-27. [Medline].

  18. Egeler RM, Wolff JE, Anderson RA, Coppes MJ. Long-term complications and post-treatment follow-up of patients with Wilms' tumor. Semin Urol Oncol. Feb 1999;17(1):55-61. [Medline].

  19. Evans AE, Norkool P, Evans I, et al. Late effects of treatment for Wilms' tumor. A report from the National Wilms' Tumor Study Group. Cancer. Jan 15 1991;67(2):331-6. [Medline].

  20. Paulino AC, Wen BC, Brown CK, et al. Late effects in children treated with radiation therapy for Wilms' tumor. Int J Radiat Oncol Biol Phys. Mar 15 2000;46(5):1239-46. [Medline].

  21. Green DM. The treatment of stages I-IV favorable histology Wilms' tumor. J Clin Oncol. Apr 15 2004;22(8):1366-72. [Medline].

  22. Montgomery BT, Kelalis PP, Blute ML, et al. Extended followup of bilateral Wilms tumor: results of the National Wilms Tumor Study. J Urol. Aug 1991;146(2 ( Pt 2)):514-8. [Medline].

  23. Paulino AC, Wilimas J, Marina N, et al. Local control in synchronous bilateral Wilms tumor. Int J Radiat Oncol Biol Phys. Oct 1 1996;36(3):541-8. [Medline].

  24. Paulino AC, Thakkar B, Henderson WG. Metachronous bilateral Wilms' tumor: the importance of time interval to the development of a second tumor. Cancer. Jan 15 1998;82(2):415-20. [Medline].

  25. Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol. May 20 2006;24(15):2352-8. [Medline].

  26. Green DM, Cotton CA, Malogolowkin M, et al. Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group. Pediatr Blood Cancer. May/ 2007;48:493-9. [Medline].

  27. Malogolowkin M, Cotton CA, Green DM, et al. Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group. Pediatr Blood Cancer. Feb 2008;50(2):236-41. [Medline].

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Further Reading

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Keywords

Wilms tumor, Wilms' tumor, nephroblastoma, synchronous bilateral Wilms tumor, metachronous bilateral Wilms tumor, National Wilms Tumor Study, NWTS, National Wilms Tumor Study Group, NWTSG, International Society of Pediatric Oncology, SIOP, WAGR syndrome, Beckwith-Wiedemann syndrome, BWS, Denys-Drash syndrome, Denys-Drash syndrome, visceromegaly, macroglossia, hyperinsulinemic hypoglycemia, urinary tract infection, varicocele, hypertension, hypotension, cryptorchidism, horseshoe kidney, hypospadias

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Contributor Information and Disclosures

Author

Arnold C Paulino, MD, Associate Professor, Department of Radiology, Division of Radiation Oncology, Associate Professor of Pediatrics, Baylor College of Medicine; Consulting Staff, Methodist Hospital and Texas Children's Hospital
Arnold C Paulino, MD is a member of the following medical societies: American College of Radiology, American Medical Association, American Radium Society, American Society for Therapeutic Radiology and Oncology, Children's Oncology Group, Connective Tissue Oncology Society, and Radiological Society of North America
Disclosure: Nothing to disclose.

Coauthor(s)

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Steven K Bergstrom, MD, Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland
Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
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