Wilms' tumor

Did You Know?

• Sidney Farber and colleagues achieved the first remissions in Wilms' tumor in the 1950s using actinomycin D with surgery and radiation, raising cure rates from 40 to 89 percent.
• The use of CT scan for diagnosing Wilms' tumor began in the early 1970s, initiated by Italian physician Mario Costici.

Pathogenesis

Wilms' tumor arises from syndromic or non-syndromic causes. Syndromic cases involve alterations to genes such as WT1 or WT2 and present with additional signs; non-syndromic cases occur without other symptoms. Many tumors develop from nephrogenic rests, fragments of tissue that form before birth and become cancerous afterward. Bilateral tumors and those linked to syndromes like Denys-Drash syndrome are strongly associated with these rests. Most nephroblastomas are unilateral, and fewer than 5% are bilateral, though Denys-Drash syndrome often involves multiple or bilateral tumors. The tumors are typically encapsulated and vascularized, do not cross the midline, and may metastasize to the lung. Rupture risks bleeding and peritoneal spread. Pathologically, a triphasic Wilms' tumor contains blastema, mesenchyme (stroma), and epithelium, with abortive tubules and glomeruli in a spindled cell stroma. The stroma may include striated muscle, cartilage, bone, fat, or fibrous tissue. Tumors are classified as favorable (well-developed components) or anaplastic (diffuse anaplasia).

Diagnosis

Most children present with an asymptomatic abdominal mass noticed by a family member or healthcare professional. In those with predisposing syndromes, tumors may be found during routine screening. Diagnosis involves medical history, physical exam, and blood, urine, and imaging tests. Ultrasound is typically the first imaging study to confirm an intrarenal mass, followed by CT or MRI for more detail. Definitive diagnosis comes from tissue examination, but biopsy is often avoided due to risk of spreading cancer cells. In North America, treatment begins with nephrectomy; in Europe, chemotherapy precedes nephrectomy. Staging describes tumor extent and guides prognosis and treatment. Stage I (43% of cases) requires tumor limited to the kidney, intact capsule, no rupture or biopsy before removal, no lymph-vascular involvement, and clear margins. Stage II (23%) involves tumor extending beyond the kidney but completely excised, with possible renal sinus vessel or soft tissue involvement. Stage III (20%) includes inoperable primary tumor, lymph node metastasis, positive margins, tumor spillage, or prior biopsy.

Treatment and prognosis

Overall 5-year survival is about 90%, though prognosis depends on stage and treatment. Early removal improves outcomes. Loss of heterozygosity (LOH) for chromosomes 1p and 16q identifies patients with higher relapse and death risk, and this LOH status is used with stage to tailor treatment intensity. More aggressive stages may sometimes show better outcomes due to more intensive therapy or study variability. Stage V prognosis is comparable to stage IV. For relapsed standard-risk disease, 4-year survival is about 80%.

Epidemiology

Wilms tumor is the most common malignant renal tumor in children. It affects about one person per 10,000 worldwide before age 15. People of African descent may have slightly higher rates. Peak age is 3 to 4 years, with most cases before age 10. Genetic predisposition occurs in individuals with aniridia due to deletions on chromosome 11 band p13. Rare genetic syndromes increase risk, and screening guidelines vary by country.