This cancer treatment information summary provides an overview of the prognosis, diagnosis, classification, staging, and treatment of Wilms’ tumor and other childhood kidney tumors (clear cell sarcoma of the kidney [CCSK], rhabdoid tumor of the kidney, neuroepithelial tumor of the kidney [NETK], and cystic partially-differentiated nephroblastoma). (Refer to the PDQ summary on Unusual Cancers of Childhood for more information about childhood renal cell carcinoma treatment).

The National Cancer Institute provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public. These summaries are updated regularly according to the latest published research findings by an Editorial Board of pediatric oncology specialists.

Cancer in children and adolescents is rare. Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation oncologists, pediatric medical oncologists/hematologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others in order to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. Refer to the PDQ Supportive Care summaries for specific information about supportive care for children and adolescents with cancer.

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[1] At these pediatric cancer centers, clinical trials are available for most of the types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers have been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Cancer.gov Web site.

Wilms’ tumor is a curable disease in the majority of affected children. Approximately 500 cases are diagnosed in the United States annually. More than 90% of patients survive 4 years after diagnosis which is an improvement over the 80% survival observed from 1975 to 1984.[2] The prognosis is related not only to the stage of disease at diagnosis, the histopathologic features of the tumor, patient age, and tumor size, but also to the team approach to each patient by the pediatric surgeon, radiation oncologist, and pediatric oncologist.[2-4] Previous clinical trials have, in part, evaluated with some success whether reduced therapy is sufficient to control disease in patients with early-stage, favorable-histology Wilms’ tumor.[5,6] Ongoing clinical trials are evaluating biologic factors in the development of Wilms’ tumor, clear cell sarcoma, and rhabdoid tumor of the kidney.[2]

Wilms’ tumor normally develops in otherwise healthy children but just under 10% occur in individuals with recognized malformations. The phenotypes associated with Wilms’ tumor can be classified as overgrowth or nonovergrowth syndromes. Overgrowth syndromes are the result of excessive prenatal and postnatal somatic growth, and result in macroglossia, nephromegaly, and hemihypertrophy. The two most common overgrowth disorders associated with Wilms’ tumor are Beckwith-Wiedemann syndrome and isolated hemihypertrophy.[7-11] Others include Perlman syndrome, Sotos syndrome, and Simpson-Golabi-Behemel syndrome. Nonovergrowth disorders associated with Wilms’ tumor include isolated aniridia, trisomy 18, aniridia in combination with genitourinary malformations, and mental retardation (AGR) syndrome, Bloom syndrome, and Denys-Drash syndrome.[12] Children with a predisposition to develop Wilms’ tumor (e.g., Beckwith-Wiedemann syndrome, hemihypertrophy, aniridia) should be screened with ultrasound every 3 months until they reach 8 years of age.[7-11]

Wilms’ tumor (hereditary or sporadic) appears to result from changes in 1 or more of several genes. Specific germ-line mutations in 1 of these genes (Wilms’ tumor gene-1, WT1) located on the short arm of chromosome 11 (band 11p13) are not only associated with Wilms’ tumor but also cause a variety of genitourinary abnormalities such as cryptorchidism and hypospadias,[13] and the rare Denys-Drash syndrome. A gene that causes aniridia is located near the WT1 gene on chromosome 11p13, and deletions encompassing the WT1 and aniridia genes may explain the association between aniridia and Wilms’ tumor. Patients with aniridia or hemihypertrophy should be screened with ultrasound every 3 months until they reach 8 years of age.[7] Children with Wilms’ Aniridia-Genitourinary abnormalities-(mental) Retardation (WAGR) syndrome are at increased risk of eventually developing renal failure and should be monitored. Patients with Wilms’ tumor and aniridia without genitourinary abnormalities are at lesser risk but should be monitored.[14] There appears to be a second Wilms’ tumor gene at or near the Beckwith-Wiedemann gene locus on chromosome 11p15, and children with Beckwith-Wiedemann syndrome are at increased risk for developing Wilms’ tumor. Approximately one fifth of patients with Beckwith-Wiedemann syndrome who develop Wilms’ tumor present with bilateral disease, primarily at diagnosis, although metachronous recurrence is also observed.[7-9]

Approximately one third of Wilms’ tumors have loss of genetic material in the tumor cells from the short arm of chromosome 11, encompassing 1 or both of the Wilms’ tumor gene regions on this chromosome. Genes on other chromosomes may also have an etiologic role in Wilms’ tumor, and loss of genetic material from chromosome 16 and/or chromosome 1p occurs in some tumors.[15,16] Many Wilms’ tumors appear to arise from abnormally retained embryonic kidney precursor cells arranged in clusters termed nephrogenic rests. The different genetic lesions are associated with different subtypes of nephrogenic rests.[17] Wilms’ tumors that develop from intralobar nephrogenic rests generally contain heterologous elements such as smooth muscle, cartilage, and fat cells, and are associated with loss of DNA on the short arm of chromosome 11p and occasionally with WT1 gene mutation. In contrast, Wilms’ tumors that develop from perilobar nephrogenic rests, which appear to reflect a slightly later stage in renal embryonic development and are generally found in older children are associated with loss of imprinting of the IGF2 gene, which stimulates cell proliferation. Usually the maternal copy of IGF2 is imprinted, that is, not expressed in the embryo, and when it is expressed in the tumor, twice as much IGF2 RNA is made. Perilobar rests are also associated with Wilms’ tumors in children with Beckwith-Wiedemann syndrome.[18]

Despite the number of genes that appear to be involved in the development of Wilms’ tumor, hereditary Wilms’ tumor is uncommon, with 1% to 2% of patients having a positive family history for Wilms’ tumor.[19,20] The risk of Wilms’ tumor among offspring of persons who have had unilateral (i.e., sporadic) tumors is quite low (<2%).[21] Siblings of children with Wilms’ tumor have a low likelihood of developing Wilms’ tumor.[19] About 4% to 5% of patients have bilateral Wilms’ tumors, but these are not usually hereditary.[19,20] Many bilateral tumors are present at the time Wilms’ tumor is first diagnosed (i.e., synchronous), but a second Wilms’ tumor may also develop later in the remaining kidney of 1% to 3% of children treated successfully for Wilms’ tumor. The incidence of such metachronous bilateral Wilms’ tumors is much higher in children whose original Wilms’ tumor was diagnosed at younger than 12 months and/or whose resected kidney contains nephrogenic rests. Periodic abdominal ultrasound is recommended for early detection of metachronous bilateral Wilms’ tumor as follows: children with nephrogenic rests in the resected kidney (if younger than 48 months at initial diagnosis) - every 3 months for 6 years; children with nephrogenic rests in the resected kidney (if older than 48 months at initial diagnosis) - every 3 months for 4 years; other patients - every 6 months for 2 years, then yearly for an additional 1 to 3 years.[22,23]

Clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, neuroepithelial tumor of the kidney, and cystic partially-differentiated nephroblastoma (see descriptions in the Cellular Classification section) are childhood renal tumors unrelated to Wilms’ tumor. Because of their renal location, they have been treated on clinical trials developed by the National Wilms’ Tumor Study Group. The approach to their treatment, however, is distinctive from that of Wilms’ tumor, and requires timely and accurate diagnosis.

References

1. Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99 (1): 139-41, 1997.  [PUBMED Abstract]
   
   
2. Green DM, Children's Oncology Group: Phase III Multimodality Therapy Based on Histology, Stage, Age, and Tumor Size in Children With Wilms' Tumor, Clear Cell Sarcoma of the Kidney, or Rhabdoid Tumors of the Kidney, COG-Q9401, Clinical trial, Closed.  [PDQ Clinical Trial]
   
   
3. Ritchey ML, Haase GM, Shochat S: Current management of Wilms' tumor. Semin Surg Oncol 9 (6): 502-9, 1993 Nov-Dec.  [PUBMED Abstract]
   
   
4. Breslow N, Sharples K, Beckwith JB, et al.: Prognostic factors in nonmetastatic, favorable histology Wilms' tumor. Results of the Third National Wilms' Tumor Study. Cancer 68 (11): 2345-53, 1991.  [PUBMED Abstract]
   
   
5. D'Angio GJ, Breslow N, Beckwith JB, et al.: Treatment of Wilms' tumor. Results of the Third National Wilms' Tumor Study. Cancer 64 (2): 349-60, 1989.  [PUBMED Abstract]
   
   
6. Mitchell C, Jones PM, Kelsey A, et al.: The treatment of Wilms' tumour: results of the United Kingdom Children's cancer study group (UKCCSG) second Wilms' tumour study. Br J Cancer 83 (5): 602-8, 2000.  [PUBMED Abstract]
   
   
7. Green DM, Breslow NE, Beckwith JB, et al.: Screening of children with hemihypertrophy, aniridia, and Beckwith-Wiedemann syndrome in patients with Wilms tumor: a report from the National Wilms Tumor Study. Med Pediatr Oncol 21 (3): 188-92, 1993.  [PUBMED Abstract]
   
   
8. DeBaun MR, Siegel MJ, Choyke PL: Nephromegaly in infancy and early childhood: a risk factor for Wilms tumor in Beckwith-Wiedemann syndrome. J Pediatr 132 (3 Pt 1): 401-4, 1998.  [PUBMED Abstract]
   
   
9. DeBaun MR, Tucker MA: Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry. J Pediatr 132 (3 Pt 1): 398-400, 1998.  [PUBMED Abstract]
   
   
10. Porteus MH, Narkool P, Neuberg D, et al.: Characteristics and outcome of children with Beckwith-Wiedemann syndrome and Wilms' tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol 18 (10): 2026-31, 2000.  [PUBMED Abstract]
    
    
11. Hoyme HE, Seaver LH, Jones KL, et al.: Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review. Am J Med Genet 79 (4): 274-8, 1998.  [PUBMED Abstract]
    
    
12. Clericuzio CL: Clinical phenotypes and Wilms tumor. Med Pediatr Oncol 21 (3): 182-7, 1993.  [PUBMED Abstract]
    
    
13. Diller L, Ghahremani M, Morgan J, et al.: Constitutional WT1 mutations in Wilms' tumor patients. J Clin Oncol 16 (11): 3634-40, 1998.  [PUBMED Abstract]
    
    
14. Breslow NE, Takashima JR, Ritchey ML, et al.: Renal failure in the Denys-Drash and Wilms' tumor-aniridia syndromes. Cancer Res 60 (15): 4030-2, 2000.  [PUBMED Abstract]
    
    
15. Coppes MJ, Haber DA, Grundy PE: Genetic events in the development of Wilms' tumor. N Engl J Med 331 (9): 586-90, 1994.  [PUBMED Abstract]
    
    
16. Grundy PE, Telzerow PE, Breslow N, et al.: Loss of heterozygosity for chromosomes 16q and 1p in Wilms' tumors predicts an adverse outcome. Cancer Res 54 (9): 2331-3, 1994.  [PUBMED Abstract]
    
    
17. Beckwith JB: Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations. Am J Med Genet 79 (4): 268-73, 1998.  [PUBMED Abstract]
    
    
18. Ravenel JD, Broman KW, Perlman EJ, et al.: Loss of imprinting of insulin-like growth factor-II (IGF2) gene in distinguishing specific biologic subtypes of Wilms tumor. J Natl Cancer Inst 93 (22): 1698-703, 2001.  [PUBMED Abstract]
    
    
19. Bonaïti-Pellié C, Chompret A, Tournade MF, et al.: Genetics and epidemiology of Wilms' tumor: the French Wilms' tumor study. Med Pediatr Oncol 20 (4): 284-91, 1992.  [PUBMED Abstract]
    
    
20. Breslow NE, Beckwith JB: Epidemiological features of Wilms' tumor: results of the National Wilms' Tumor Study. J Natl Cancer Inst 68 (3): 429-36, 1982.  [PUBMED Abstract]
    
    
21. Li FP, Williams WR, Gimbrere K, et al.: Heritable fraction of unilateral Wilms tumor. Pediatrics 81 (1): 147-9, 1988.  [PUBMED Abstract]
    
    
22. Paulino AC, Thakkar B, Henderson WG: Metachronous bilateral Wilms' tumor: the importance of time interval to the development of a second tumor. Cancer 82 (2): 415-20, 1998.  [PUBMED Abstract]
    
    
23. 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 85 (7): 1616-25, 1999.  [PUBMED Abstract]
    
    

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