Incidence

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  Renal tumors comprise approximately 6% of all childhood cancers and nearly 10% of all malignancies among children aged 1–4 years.

  
  
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  Wilms’ tumor (nephroblastoma) is the most common primary renal tumor of childhood and the sixth most common childhood malignancy in the United States.

  
  
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  The male to female ratio 0.92:1.00 in unilateral Wilms’ and 0.6:1.00 in bilateral Wilms’ tumor.

  
  
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  Wilms’ tumor, clear cell sarcoma of the kidney, and malignant rhabdoid tumor of the kidney occur predominantly in younger children and are rarely seen after 10 years of age. The majority of renal tumors occurring in adolescents and young adults are renal cell carcinomas (RCCs).

  
  
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  Seventy-eight percent of children with Wilms’ tumor are diagnosed at 1–5 years of age, with a peak incidence occurring between 3 and 4 years of age. The median age of presentation is 44 months in unilateral disease and 32 months in bilateral disease.

  
  
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  Wilms’ tumor is usually sporadic, but 1% of cases are familial.

WAGR Syndrome

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  The syndrome consists of Wilms’ tumor, aniridia, genitourinary malformations, and mental retardation, but other associated anomalies are seen.

  
  
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  A chromosomal deletion has been consistently found in the short arm of chromosome 11 (11p13 deletion). This area encompasses both the WT1 and PAX6 genes; WT1 is implicated in Wilms’ tumor and PAX6 is implicated in aniridia.

  
  
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  Aniridia is present in 1.2% of children with Wilms’ tumor.

  
  
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  A child with sporadic aniridia has a 5% chance of developing Wilms’ tumor; most cases of sporadic aniridia have PAX6 mutations/deletions but not WT1 deletions. A child with WT1 deletion has a 30–40% risk of Wilms’ tumor.

  
  
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  WAGR syndrome is associated with focal segmental glomerular sclerosis and renal failure in 30–40% of individuals 20 years following Wilms’ tumor diagnosis.

Denys–Drash Syndrome

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  The syndrome consists of Wilms’ tumor, early renal failure with mesangial sclerosis, and pseudohermaphroditism.

  
  
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  Associated with point mutations of the WT1 gene.

  
  
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  Associated with 90% risk of Wilms’ tumor.

Beckwith–Wiedemann Syndrome

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  This syndrome consists of

  
  
  
  
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    Hyperplastic fetal visceromegaly involving the kidney, adrenal cortex, pancreas, gonads, and liver, hemihypertrophy, macroglossia, abdominal wall defects (omphalocele, umbilical hernia, diastasis recti), ear pits or creases, microcephaly, mental retardation, hypoglycemia, and postnatal somatic gigantism.

    
    
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    Predisposition to embryonal tumors (Wilms’ tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma) and adrenocortical carcinoma. Risk of Wilms’ tumor is approximately 5%.

  
  
  
  
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  The Beckwith–Wiedemann locus at chromosome 11p15.5 contains a cluster of imprinted genes ( IGF2 , H19 , CDKN1C , KCNQ10T1 , and KCNQ1 ). Various genetic and epigenetic changes can lead to the phenotypic features of the syndrome. This locus is often referred to as WT2.

Screening of Children with WAGR, Denys–Drash, and Beckwith–Wiedemann Syndromes

Among individuals with Beckwith–Wiedemann syndrome and Wilms’ tumor, 93% develop the tumor by 8 years of age. Therefore, children with Beckwith–Wiedemann syndrome should have an abdominal ultrasound every 3 months until 8 years of age to evaluate for abdominal malignancies. Serum α-fetoprotein level should be tested during infancy and early childhood because of the association with hepatoblastoma. 11p15 mutation and methylation analysis should be considered because new data indicate that certain Beckwith–Wiedemann epigenetic changes are associated with a higher risk of tumor development than others. Among individuals with WAGR syndrome and Wilms’ tumor, 90% develop the tumor by age 4 and 98% by age 7 years. Based on this information, children with WAGR and Denys–Drash syndromes should have screening abdominal ultrasounds every 3 months until 5 years of age, but screening may be extended if Wilms’ tumor precursor lesions (nephrogenic rests) are identified. Children with sporadic aniridia should be referred for FISH (fluorescence in situ hybridization) of the WT1 gene because if WT1 is not deleted, the risk of Wilms’ tumor is similar to the population risk.

Histologic Findings

Anaplastic histology is identified by the presence of cells with nuclear enlargement, nuclear atypia, and irregular mitotic figures. Focal anaplasia is distinguished from diffuse anaplasia by the distribution of anaplastic elements. Anaplasia well-contained within a single region of the tumor is considered focal anaplasia and anaplasia found in multiple regions of the tumor or outside the renal parenchyma is considered diffuse anaplasia.

FH, as the name implies, is associated with the best prognosis, followed by focal anaplasia, followed by diffuse anaplasia, which has significantly worse prognosis.

A diagnosis of diffuse anaplasia is made if the following characteristics are present:

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  Anaplasia in any extrarenal site, including vessels of the renal sinus, extracapsular infiltrates, or nodal or distant metastases.

  
  
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  Anaplasia in a random biopsy specimen.

  
  
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  Anaplasia unequivocally expressed in one region of the tumor, but with extreme nuclear pleomorphism approaching the criteria of anaplasia (extreme nuclear unrest) elsewhere in the lesion.

  
  
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  Anaplasia in more than one tumor slide, unless (i) it is known that every slide showing anaplasia came from the same focused region of the tumor or (ii) anaplastic foci on the various slides are minute and surrounded on all sides by non-anaplastic tumor.