Renal Tumors, Children

CHAPTER 38 Renal Tumors, Children

Jessica C. Lloyd, MD and Jonathan C. Routh, MD, MPH

What is the incidence of Wilms tumor in children in North America?

Roughly 500 cases of Wilms tumor occur in North America per year, giving an incidence of roughly 8 per 1,000,000. Wilms tumor is the most common malignant pediatric renal tumor, and accounts for 7% of all childhood cancers.

How often are congenital anomalies associated with Wilms tumor?

Fifteen percent of cases. Congenital anomalies are much more common in patients with bilateral or simultaneous multifocal tumors.

What are the major Wilms tumor study groups?

In North America, the renal committee of the Children’s Oncology Group (COG) is the major cooperative Wilms tumor study group. In Europe, the International Society of Pediatric Oncology (SIOP) is the major cooperative Wilms tumor study group.

What is the relationship of aniridia to Wilms tumor?

Aniridia is caused by an abnormality of the PAX6 gene located adjacent to WT1, and is seen in 1% of patients with Wilms tumors. Of patients with aniridia, 40% of those having a chromosomal deletion that includes the locus for WT1 will develop Wilms tumor. Conversely, those with a normal WT1 do not develop Wilms tumor.

What genitourinary abnormalities are associated with Wilms tumor?

Horseshoe kidney and other renal fusion anomalies, renal ectopia, Mullerian duct anomalies, hypospadias, and cryptorchidism have been reported in 5% of cases.

How frequently does hemihypertrophy occur with Wilms tumor?

Three percent of cases. Hemihypertrophy can be complete, partial, unilateral, or crossed. It is more common in females than males. This is also associated with 11p abnormalities and may occur as isolated hemihypertrophy or in the context of Beckwith-Wiedemann syndrome (BWS).

What skin lesions are associated with Wilms tumor?

Hemangiomas, cafe au lait spots, neurofibromas, and nevi are seen in 3% of cases.

What is Beckwith-Wiedemann syndrome?

BWS is a rare congenital overgrowth syndrome defined by macroglossia, anterior abdominal wall defects (ranging from umbilical hernia to omphalocele), visceromegaly (particularly hepatomegaly and nephromegaly), posterior helical indentations (pits of the external ear), neonatal hypoglycemia, and hemihypertrophy. Most cases are sporadic; 15% have autosomal dominant inheritance. BWS is associated with WT2 abnormalities, and 10% of children with BWS will develop a pediatric tumor, usually Wilms tumor, adrenal carcinoma, hepatoblastoma, and/or rhabdomyosarcoma.

What other syndromes are associated with an increased incidence of Wilms tumor?

Microcephaly, Perlman, Sotos, and Simpson–Golabi–Behmel syndromes, developmental delay, spina bifida, intersex, trisomy 18, mixed gonadal dysgenesis, and nephrotic syndrome.

What is the risk of Wilms tumor development in the following syndromes/conditions: WAGR, Denys–Drash, Perlman, Beckwith–Wiedemann, Simpson–Golabi–Behmel, Li–Fraumeni, Sotos, and neurofibromatosis?

WAGR: 50%

Denys–Drash: 50%

Perlman: >20%

Beckwith–Wiedemann: 5% to 10%

Simpson–Golabi–Behmel: 10% (in males)

Li–Fraumeni: low

Sotos: low

Neurofibromatosis: low

True/False: No study has recommended screening ultrasound for Wilms tumor.

False. Screening with serial renal ultrasonography has been recommended for children suffering from conditions that confer a ≥5% chance of developing Wilms tumor. Serial ultrasounds are recommended from the age of diagnosis until 5 years of age, at 3 to 4 month intervals. In children with Beckwith–Wiedemann Syndrome, Simpson–Golabi–Behmel syndrome, and familial Wilms histories, screenings are recommended through age 7 years.

Has a familial basis for Wilms tumor been described?

Yes, approximately 1% of patients have a positive family history for Wilms tumor. This is thought to be inherited in an autosomal dominant manner, but with variable penetrance. Familial Wilms tumor often presents at an earlier age, with an increased frequency of bilateral disease.

What chromosomal abnormalities have been associated with Wilms tumor?

Deletions in chromosome 11p13 are most commonly reported. The gene at this locus has been cloned and designated the WT1 tumor suppressor gene. A second Wilms tumor locus, WT2, has been also identified on chromosome 11p15. 20% of Wilms tumor patients have loss of heterozygosity on chromosome 16q and 11% of Wilms tumor patients have loss of heterozygosity on chromosome 1p.

What is the function of the WT1 gene?

WT1 is important for normal kidney and gonadal development. It encodes a zinc-finger transcription factor that is expressed in the kidneys, gonads, spleen, and mesothelium. WT1 is necessary for ureteric bud outgrowth and is also important in nephrogenesis.

What is WAGR syndrome?

The WAGR syndrome is seen in children with Wilms tumor, Aniridia, Genitourinary malformation, and mental Retardation. Most children with WAGR syndrome have a chromosomal deletion on chromosome 11p13. WAGR patients are at high risk of renal failure and of bilateral tumors.

What is Denys–Drash syndrome?

Denys–Drash is a rare syndrome which consists of the triad of ambiguous genitalia (disorders of sex development, most commonly pure gonadal dysgenesis), nephrotic syndrome (renal or diffuse mesangial sclerosis), and Wilms tumor. It is associated with mutations of the zinc-finger DNA-binding region of WT1 on chromosome 11p13. Children with Denys–Drash are at high risk of end-stage renal disease following treatment for their Wilms tumor.

What is the incidence of bilateral Wilms tumors?

Bilateral disease occurs in 5% of patients (4% synchronous, 1% metachronous).

Do sporadic, heritable, and bilateral cases of Wilms tumor have varying mean ages of presentation?

Yes. Bilateral and heritable cases of Wilms tumors present with a mean age of 2.5 years, whereas sporadic cases have a mean age of presentation of 3.5 years.

How common is Wilms tumor in neonates?

Wilms tumor is rare in the newborn. The more likely solid renal tumor in this age group is congenital mesoblastic nephroma, while the most common solid abdominal tumor is neuroblastoma.

True/False: Wilms tumor occurs most commonly after the age of 6 years.

False. Fifty percent of patients are 1 to 3 years old, 75% are younger than 5 years, and 98% are younger than 10 years at diagnosis. The peak incidence occurs between 1 and 3 years.

What is the prognostic significance of Wilms tumors occurring in older children?

Patients presenting at an older age typically have a more advanced tumor that is less responsive to treatment.

What are the common presenting symptoms for patients with Wilms tumors?

Abdominal mass is most common (90%), followed by hypertension (0%-60%), pain (20%-30%), nausea and vomiting (15%), fever (10%-20%), and gross hematuria (5%-10%).

An acquired von Willebrand disease is observed in what percentage of newly diagnosed Wilms tumor patients?

In 5% to 10% of patients. All newly diagnosed patients should undergo a coagulation screen with platelet count, bleeding time, prothrombin time, and activated partial thromboplastin time prior to surgery.

What percentage of Wilms tumors have a tumor diameter greater than 5 cm?

90%.

How frequently does Wilms tumor display venous extension?

Four percent of patients have a tumor thrombus extending to the renal vein, inferior vena cava, or right atrium.

What are the common sites of metastasis for Wilms tumor?

The most common site of distant metastasis is the lungs. Pulmonary metastases are present at diagnosis in 8% of patients. The other common site of metastasis is the liver.

What histopathologic features are classically seen with Wilms tumor?