Presentation, diagnosis, and staging of Wilms tumor
- Murali Chintagumpala, MD
Murali Chintagumpala, MD
- Professor of Pediatric Hematology and Oncology
- Baylor College of Medicine
- Jodi A Muscal, MD
Jodi A Muscal, MD
- Assistant Professor of Pediatric Hematology and Oncology
- Baylor College of Medicine
Wilms tumor is the most common renal malignancy in children and the fourth most common childhood cancer . The epidemiology, presentation, diagnosis, and staging of Wilms tumor will be reviewed here. The treatment and outcome of Wilms tumor are discussed separately. (See "Treatment and prognosis of Wilms tumor".)
In the United States, the annual incidence of renal tumors is about eight cases per million children younger than 15 years , accounting for 7 percent of all childhood malignancies  and for 500 new cases per year in North America [1,3-6]. Wilms tumor is the most common renal malignancy in children under the age of 15 years, accounting for about 95 percent of all cases. In contrast, renal cell carcinoma is more common in the 15 to 19-year-old age group .
In the United States, two-thirds of cases of Wilms tumor are diagnosed before five years of age, and 95 percent before 10 years of age . In patients with unilateral involvement, the median age at diagnosis is 43 months in girls and 37 months in boys . Children with bilateral disease are diagnosed at an earlier age (median age, girls at 31 months and boys at 24 months) . Patients with associated congenital anomalies, such as aniridia or genitourinary abnormalities, are also diagnosed at an earlier age .
The risk of developing Wilms tumor varies among ethnic groups, with a greater risk in African-Americans and a lower risk in the Asian population [1,8,9]. Epigenetic differences may contribute to the lower rate of disease in Asian children, as demonstrated by a study that reported infrequent loss of IGF2 imprinting in tumors from Asian patients . (See 'Genetics' below.)
Associated congenital syndromes — Wilms tumor is primarily a sporadic disease, and only 1 to 2 percent of individuals with Wilms tumor have a relative with the disease . In some children, Wilms tumor occurs as a part of a multiple malformation syndrome . These syndromes include WAGR, Denys-Drash, and Beckwith-Wiedemann syndromes.
- Grovas A, Fremgen A, Rauck A, et al. The National Cancer Data Base report on patterns of childhood cancers in the United States. Cancer 1997; 80:2321.
- Bernstein L, Linet M, Smith MA, et al. Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995, SEER Program. Bethesda, MD, National Cancer Institute 1999. p.79.
- Perlman EJ. Pediatric renal tumors: practical updates for the pathologist. Pediatr Dev Pathol 2005; 8:320.
- Kalapurakal JA, Dome JS, Perlman EJ, et al. Management of Wilms' tumour: current practice and future goals. Lancet Oncol 2004; 5:37.
- Gurney JG, Davis S, Severson RK, et al. Trends in cancer incidence among children in the U.S. Cancer 1996; 78:532.
- Ries LA, Smith MA, Gurney JG, et al. Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975-1995, National Cancer Institute, SEER Program. NIH Pub. No. 99-4649. Maryland 1999.
- Breslow N, Beckwith JB, Ciol M, Sharples K. Age distribution of Wilms' tumor: report from the National Wilms' Tumor Study. Cancer Res 1988; 48:1653.
- Goodman MT, Yoshizawa CN, Kolonel LN. Ethnic patterns of childhood cancer in Hawaii between 1960 and 1984. Cancer 1989; 64:1758.
- Stiller CA, Parkin DM. Geographic and ethnic variations in the incidence of childhood cancer. Br Med Bull 1996; 52:682.
- Fukuzawa R, Breslow NE, Morison IM, et al. Epigenetic differences between Wilms' tumours in white and east-Asian children. Lancet 2004; 363:446.
- Huff V. Wilms' tumours: about tumour suppressor genes, an oncogene and a chameleon gene. Nat Rev Cancer 2011; 11:111.
- Scott RH, Stiller CA, Walker L, Rahman N. Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genet 2006; 43:705.
- MILLER RW, FRAUMENI JF Jr, MANNING MD. ASSOCIATION OF WILMS'S TUMOR WITH ANIRIDIA, HEMIHYPERTROPHY AND OTHER CONGENITAL MALFORMATIONS. N Engl J Med 1964; 270:922.
- Fischbach BV, Trout KL, Lewis J, et al. WAGR syndrome: a clinical review of 54 cases. Pediatrics 2005; 116:984.
- Breslow NE, Norris R, Norkool PA, et al. Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report from the National Wilms Tumor Study Group. J Clin Oncol 2003; 21:4579.
- Bliek J, Gicquel C, Maas S, et al. Epigenotyping as a tool for the prediction of tumor risk and tumor type in patients with Beckwith-Wiedemann syndrome (BWS). J Pediatr 2004; 145:796.
- Koufos A, Grundy P, Morgan K, et al. Familial Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5. Am J Hum Genet 1989; 44:711.
- Astuti D, Morris MR, Cooper WN, et al. Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nat Genet 2012; 44:277.
- Lapunzina P. Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. Am J Med Genet C Semin Med Genet 2005; 137C:53.
- Li M, Shuman C, Fei YL, et al. GPC3 mutation analysis in a spectrum of patients with overgrowth expands the phenotype of Simpson-Golabi-Behmel syndrome. Am J Med Genet 2001; 102:161.
- Neri G, Gurrieri F, Zanni G, Lin A. Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome. Am J Med Genet 1998; 79:279.
- Byrne J, Nicholson HS. Excess risk for Mullerian duct anomalies in girls with Wilms tumor. Med Pediatr Oncol 2002; 38:258.
- Beckwith JB, Kiviat NB, Bonadio JF. Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms' tumor. Pediatr Pathol 1990; 10:1.
- Beckwith JB. Precursor lesions of Wilms tumor: clinical and biological implications. Med Pediatr Oncol 1993; 21:158.
- Coppes MJ, Haber DA, Grundy PE. Genetic events in the development of Wilms' tumor. N Engl J Med 1994; 331:586.
- Riccardi VM, Sujansky E, Smith AC, Francke U. Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion. Pediatrics 1978; 61:604.
- Varanasi R, Bardeesy N, Ghahremani M, et al. Fine structure analysis of the WT1 gene in sporadic Wilms tumors. Proc Natl Acad Sci U S A 1994; 91:3554.
- Shuman C, Smith AC, Steele L, et al. Constitutional UPD for chromosome 11p15 in individuals with isolated hemihyperplasia is associated with high tumor risk and occurs following assisted reproductive technologies. Am J Med Genet A 2006; 140:1497.
- Vuononvirta R, Sebire NJ, Dallosso AR, et al. Perilobar nephrogenic rests are nonobligate molecular genetic precursor lesions of insulin-like growth factor-II-associated Wilms tumors. Clin Cancer Res 2008; 14:7635.
- Scott RH, Douglas J, Baskcomb L, et al. Constitutional 11p15 abnormalities, including heritable imprinting center mutations, cause nonsyndromic Wilms tumor. Nat Genet 2008; 40:1329.
- Malkin D, Sexsmith E, Yeger H, et al. Mutations of the p53 tumor suppressor gene occur infrequently in Wilms' tumor. Cancer Res 1994; 54:2077.
- Bardeesy N, Falkoff D, Petruzzi MJ, et al. Anaplastic Wilms' tumour, a subtype displaying poor prognosis, harbours p53 gene mutations. Nat Genet 1994; 7:91.
- Rahman N, Arbour L, Tonin P, et al. Evidence for a familial Wilms' tumour gene (FWT1) on chromosome 17q12-q21. Nat Genet 1996; 13:461.
- Rahman N, Abidi F, Ford D, et al. Confirmation of FWT1 as a Wilms' tumour susceptibility gene and phenotypic characteristics of Wilms' tumour attributable to FWT1. Hum Genet 1998; 103:547.
- McDonald JM, Douglass EC, Fisher R, et al. Linkage of familial Wilms' tumor predisposition to chromosome 19 and a two-locus model for the etiology of familial tumors. Cancer Res 1998; 58:1387.
- Turnbull C, Perdeaux ER, Pernet D, et al. A genome-wide association study identifies susceptibility loci for Wilms tumor. Nat Genet 2012; 44:681.
- Royer-Pokora B, Weirich A, Schumacher V, et al. Clinical relevance of mutations in the Wilms tumor suppressor 1 gene WT1 and the cadherin-associated protein beta1 gene CTNNB1 for patients with Wilms tumors: results of long-term surveillance of 71 patients from International Society of Pediatric Oncology Study 9/Society for Pediatric Oncology. Cancer 2008; 113:1080.
- Geller JI. Genetic stratification of Wilms tumor: is WT1 gene analysis ready for prime time? Cancer 2008; 113:893.
- Fernandez C, Geller JI, Ehrlich PF, et al. Renal tumors. In: Principles and Practice of Pediatric Oncology, 6th ed, Pizzo P, Poplack D (Eds), Lippincott Williams & Wilkins, St. Louis 2011. p.861.
- Zuppan CW, Beckwith JB, Luckey DW. Anaplasia in unilateral Wilms' tumor: a report from the National Wilms' Tumor Study Pathology Center. Hum Pathol 1988; 19:1199.
- Ganguly A, Gribble J, Tune B, et al. Renin-secreting Wilms' tumor with severe hypertension. Report of a case and brief review of renin-secreting tumors. Ann Intern Med 1973; 79:835.
- Ritchey ML, Azizkhan RG, Beckwith JB, et al. Neonatal Wilms tumor. J Pediatr Surg 1995; 30:856.
- Suresh I, Suresh S, Arumugam R, et al. Antenatal diagnosis of Wilms tumor. J Ultrasound Med 1997; 16:69.
- Tomá P, Lucigrai G, Dodero P, Lituania M. Prenatal detection of an abdominal mass by MR imaging performed while the fetus is immobilized with pancuronium bromide. AJR Am J Roentgenol 1990; 154:1049.
- Applegate KE, Ghei M, Perez-Atayde AR. Prenatal detection of a Wilms' tumor. Pediatr Radiol 1999; 29:65.
- Vadeyar S, Ramsay M, James D, O'Neill D. Prenatal diagnosis of congenital Wilms' tumor (nephroblastoma) presenting as fetal hydrops. Ultrasound Obstet Gynecol 2000; 16:80.
- Green DM, Breslow NE, Beckwith JB, Norkool P. 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 1993; 21:188.
- Scott RH, Walker L, Olsen ØE, et al. Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice. Arch Dis Child 2006; 91:995.
- Khanna G, Naranjo A, Hoffer F, et al. Detection of preoperative wilms tumor rupture with CT: a report from the Children's Oncology Group. Radiology 2013; 266:610.
- Wilimas JA, Douglass EC, Magill HL, et al. Significance of pulmonary computed tomography at diagnosis in Wilms' tumor. J Clin Oncol 1988; 6:1144.
- Green DM, Fernbach DJ, Norkool P, et al. The treatment of Wilms' tumor patients with pulmonary metastases detected only with computed tomography: a report from the National Wilms' Tumor Study. J Clin Oncol 1991; 9:1776.
- Gow KW, Barnhart DC, Hamilton TE, et al. Primary nephrectomy and intraoperative tumor spill: report from the Children's Oncology Group (COG) renal tumors committee. J Pediatr Surg 2013; 48:34.
- Grundy PE, Green DM, Dirks AC, et al. Clinical significance of pulmonary nodules detected by CT and Not CXR in patients treated for favorable histology Wilms tumor on national Wilms tumor studies-4 and -5: a report from the Children's Oncology Group. Pediatr Blood Cancer 2012; 59:631.
- Owens CM, Veys PA, Pritchard J, et al. Role of chest computed tomography at diagnosis in the management of Wilms' tumor: a study by the United Kingdom Children's Cancer Study Group. J Clin Oncol 2002; 20:2768.
- Jayabose S, Iqbal K, Newman L, et al. Hypercalcemia in childhood renal tumors. Cancer 1988; 61:788.
- Coppes MJ, Zandvoort SW, Sparling CR, et al. Acquired von Willebrand disease in Wilms' tumor patients. J Clin Oncol 1992; 10:422.
- Jonge Poerink-Stockschlader AB, Dekker I, Risseeuw-Appel IM, Hählen K. Acquired Von Willebrand disease in children with a Wilms' tumor. Med Pediatr Oncol 1996; 26:238.
- Leung RS, Liesner R, Brock P. Coagulopathy as a presenting feature of Wilms tumour. Eur J Pediatr 2004; 163:369.
- Baxter PA, Nuchtern JG, Guillerman RP, et al. Acquired von Willebrand syndrome and Wilms tumor: not always benign. Pediatr Blood Cancer 2009; 52:392.
- Isaacs H Jr. Fetal and neonatal renal tumors. J Pediatr Surg 2008; 43:1587.
- Argani P, Perlman EJ, Breslow NE, et al. Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center. Am J Surg Pathol 2000; 24:4.
- Palmer NF, Sutow W. Clinical aspects of the rhabdoid tumor of the kidney: a report of the National Wilms' Tumor Study Group. Med Pediatr Oncol 1983; 11:242.
- Vujanić GM, Sandstedt B, Harms D, et al. Rhabdoid tumour of the kidney: a clinicopathological study of 22 patients from the International Society of Paediatric Oncology (SIOP) nephroblastoma file. Histopathology 1996; 28:333.
- 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 2008; 50:1130.
- Malone PS, Duffy PG, Ransley PG, et al. Congenital mesoblastic nephroma, renin production, and hypertension. J Pediatr Surg 1989; 24:599.
- Tonk V, Wilson KS, Timmons CF, et al. Renal cell carcinoma with translocation (X;1). Further evidence for a cytogenetically defined subtype. Cancer Genet Cytogenet 1995; 81:72.
- Zhou XJ. Xp11.2 Translocation renal cell carcinomas have a poorer prognosis than non-Xp11.2 translocation carcinomas in children and young adults: a meta-analysis. Int J Surg Pathol 2010; 18:458.
- Wilson CL, Ness KK, Neglia JP, et al. Renal carcinoma after childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 2013; 105:504.
- Metzger ML, Dome JS. Current therapy for Wilms' tumor. Oncologist 2005; 10:815.
- D'Angio GJ. Pre- or post-operative treatment for Wilms tumor? Who, what, when, where, how, why--and which. Med Pediatr Oncol 2003; 41:545.
- Associated congenital syndromes
- - WAGR syndrome
- - Denys-Drash syndrome
- - Beckwith-Wiedemann syndrome
- - Other congenital anomalies
- CLINICAL PRESENTATION
- DIAGNOSTIC EVALUATION
- Laboratory testing
- DIFFERENTIAL DIAGNOSIS
- NWTS system
- SIOP staging