Description

• An embryonal renal neoplasm containing blastema, stromal, or epithelial cell types, usually affecting children <5 years of age
• Most common renal tumor in children; 5th most common pediatric malignancy
• Staging: In the US, National Wilms Tumor Study Group (NWTSG) staging is done pretreatment based on radiographic imaging and surgery, whereas in Europe/Asia, Société Internationale d'Oncologie Pédiatrique (SIOP) staging is done after neoadjuvant chemotherapy is administered (1):
  • I: Tumor limited to kidney; completely excised
  • II: Tumor extends beyond kidney; completely excised
  • III: Residual nonhematogenous tumor confined to abdomen (lymph nodes positive, spillage of tumor, peritoneal implants, extension beyond resection region)
  • IV: Hematogenous metastases
  • V: Bilateral renal involvement
• System(s) affected: Renal/Urologic
• Synonym(s): Nephroblastoma

• Occurs only in children
• Most common renal malignancy in childhood

Epidemiology

• Frequency rarer in East Asian populations than whites
• Frequency higher in black children than in whites
• Predominant age: Median age of 36.5 months
• Predominant sex: Female > Male (1.1:1)
• Represents 6–7% of all childhood cancers:
  • >80% are diagnosed before 5 years of age (median age is 3.5 years at diagnosis).
  • Wilms tumor makes up 95% of all renal cancers in children <15 years

Prevalence
US: 0.69/100,000; 7.6 cases/1 million children <15 years

Risk Factors

• Familial occurrence (1–2%):
  • These patients tend to have earlier age of onset.
  • Familial patients have greater risk of bilateral disease.
• Parental occupation (machinists, welders, motor vehicle mechanics, auto body repairmen)
• Maternal exposure to pesticides prior to child's birth (2)
• High birth weight or preterm birth (2)
• Compared with firstborn, being a 2nd or later birth may be associated with significantly decreased risk of Wilms tumor (2).

• Several congenital anomalies are known to be associated with Wilms tumor. A 2-stage mutational model has been proposed: Occurrence in either hereditary form or sporadic form. Patients with aniridia have a deletion of the short arm of chromosome 11 (11p13).
• Abnormalities of chromosome 11 at the 11p15 locus are associated with Beckwith-Wiedemann syndrome. Wilms tumor-suppressor gene (WT1) has been identified, as well as additional candidates for another suppressor gene (WT2). Chromosome band 17q12–21 has been linked to 2 kindreds with Wilms tumor, and other kindred are associated with a Wilms tumor predisposition gene at 19q13.3–q13.4. Loss of heterozygosity at chromosomes 16q and 1p is associated with adverse outcome (1)[C].

General Prevention

• Routine surveillance in patients with syndromes associated with Wilms tumor
• Routine screening with serial renal US at 3–4-month intervals has been recommended in children who have syndromes associated with an incidence of Wilms tumor >5% (3)[C].
• Routine screening with serial renal US also recommended for infants born to kindreds with familial Wilms (every 3–4 months until age 7) (3)[C].

Etiology

• Hereditary or sporadic forms of genetic mutation
• Familial form: Autosomal-dominant trait with incomplete penetrance (1%)
• Potential of parental occupational exposure (machinists, welders, motor vehicle mechanics, auto body repairmen)

Commonly Associated Conditions

• Aniridia (partial or complete absence of iris) 600× normal risk
• Hemihypertrophy (100× normal risk)
• Cryptorchidism
• Hypospadias
• Duplicated renal collecting systems
• Wiedemann-Beckwith syndrome
• Denys-Drash syndrome (nephropathy, renal failure, male pseudohermaphroditism, Wilms tumor)
• Klippel-Trenaunay syndrome
• WAGR complex (Wilms tumor, aniridia, genitourinary malformations, and mental retardation)
• Beckwith-Wiedemann syndrome (visceromegaly, macroglossia, omphalocele, hyperinsulinemic hypoglycemia)