Wilms tumor is the most common kidney cancer in children, typically striking before age 5. It accounts for about 5.7 cases per million children annually in the United States, with the highest rates (18.4 per million) in children ages 1 to 4. Most children are diagnosed after a parent or pediatrician notices a painless lump in the abdomen, and the overall outlook is good: survival rates now exceed 90% for the most common forms.
How Wilms Tumor Develops
Wilms tumor grows from cells in the kidney that failed to mature properly during fetal development. A normal kidney forms through a process where immature cells gradually specialize into the filtering structures the organ needs. In Wilms tumor, clusters of these immature cells persist after birth and eventually begin multiplying out of control. The tumor itself contains a mix of three cell types: primitive undifferentiated cells (the most aggressive component), cells attempting to form kidney tubules, and connective tissue cells. This mixture of cell types under a microscope is one of the hallmarks that distinguishes Wilms tumor from other childhood cancers.
Signs and Symptoms
The most common way Wilms tumor is discovered is as an abdominal mass that a parent notices during bathing or dressing, or that a doctor feels during a routine checkup. The child often looks and acts completely healthy otherwise, which is why the tumor can grow quite large before detection.
When symptoms do appear, abdominal pain is the most frequent, showing up in 30% to 40% of cases. About 25% of children have high blood pressure at diagnosis, which typically returns to normal once the affected kidney is removed. Blood in the urine occurs in 12% to 25% of cases. Some children also develop fever, loss of appetite, or general discomfort, but many have no symptoms at all.
Genetic and Inherited Risk Factors
Most cases of Wilms tumor occur randomly in otherwise healthy children with no family history. However, specific genetic changes increase risk substantially. Mutations in the WT1 gene on chromosome 11 are among the most well-studied. This gene normally helps kidneys develop correctly, and when it malfunctions, immature kidney cells are more likely to become cancerous.
Several rare genetic syndromes carry a particularly high risk of developing Wilms tumor:
- WAGR syndrome combines Wilms tumor risk with absent irises in the eyes, genitourinary abnormalities, and developmental delays. It results from a deletion on chromosome 11 that removes both the WT1 gene and a neighboring gene responsible for eye development.
- Denys-Drash syndrome involves kidney disease and abnormal genital development, with an approximately 90% lifetime risk of Wilms tumor.
- Beckwith-Wiedemann syndrome causes overgrowth in many tissues and is linked to changes in a different region of chromosome 11 that controls growth-related genes, including one that produces a powerful growth factor.
Children with these syndromes are typically monitored with regular kidney ultrasounds every three months during early childhood to catch tumors as early as possible.
How It Is Diagnosed
When a kidney mass is suspected, the first step is an abdominal ultrasound. This painless, radiation-free imaging test can identify where the mass originates, whether it’s solid or fluid-filled, and whether it has spread into nearby blood vessels. Ultrasound accurately detects tumor spread into the major veins 60% to 100% of the time. On ultrasound, Wilms tumor typically appears as a large, solid mass with smooth, well-defined edges and areas of varying density where the tumor has outgrown its own blood supply.
A CT scan usually follows to get more detailed information. Wilms tumor shows up as a mass that absorbs less contrast dye than the surrounding healthy kidney tissue. CT also helps surgeons plan the operation by revealing whether the tumor has spread to nearby lymph nodes, the other kidney, or the lungs. Chest imaging is standard because the lungs are the most common site of spread.
One important distinction doctors make is between Wilms tumor and neuroblastoma, another common childhood abdominal cancer. Wilms tumor pushes outward from within the kidney, while neuroblastoma typically arises from nerve tissue near the adrenal glands and pushes the kidney aside. Imaging patterns help tell them apart before any tissue is removed.
Favorable vs. Unfavorable Tumor Types
Once the tumor is examined under a microscope, the single most important factor for predicting outcome is whether the cells show a pattern called anaplasia, where cells have abnormally large, darkly stained nuclei and bizarre dividing patterns. Only 5% to 8% of Wilms tumors show anaplasia, and children with this type tend to be older at diagnosis.
Anaplasia can be focal (confined to one small area that was completely removed during surgery) or diffuse (scattered throughout the tumor). Diffuse anaplasia is the only microscopic feature classified as truly “unfavorable” and calls for more aggressive treatment. The vast majority of Wilms tumors have what’s called favorable histology, meaning the cells look abnormal but not anaplastic, and these tumors respond very well to standard therapy.
Treatment Approaches
Treatment for Wilms tumor combines surgery, chemotherapy, and sometimes radiation. The approach differs depending on where in the world you are. In North America, the Children’s Oncology Group (COG) protocol generally recommends removing the kidney first, then using the surgical findings to guide chemotherapy decisions. In Europe and much of the rest of the world, the SIOP protocol gives chemotherapy for several weeks before surgery to shrink the tumor, potentially making the operation safer and less extensive.
Both approaches produce excellent results. The North American strategy has the advantage of providing a complete, untreated tissue sample for precise staging. The European strategy reduces the risk of the tumor rupturing during surgery, which can complicate treatment.
For the most common, favorable-histology tumors caught at an early stage, chemotherapy typically involves two drugs given over several months. More advanced or aggressive tumors require additional drugs and longer treatment courses, sometimes combined with radiation to the tumor bed or lungs. In rare cases where both kidneys are affected (about 5% of patients), surgeons aim to remove the tumor from each kidney while preserving as much healthy tissue as possible.
Survival and Prognosis
Wilms tumor is one of the great success stories in pediatric cancer treatment. For children with favorable histology and localized disease, five-year survival rates exceed 90%. Even children with tumors that have spread to the lungs have survival rates around 70% to 90% depending on how well the tumor responds to chemotherapy. Unfavorable histology with diffuse anaplasia carries a lower survival rate, but intensified treatment protocols continue to improve outcomes for this group.
Long-Term Health After Treatment
Because most children survive Wilms tumor, the long-term effects of treatment become critically important. Survivors face several health considerations that require monitoring well into adulthood.
Heart health is a key concern for children who received certain chemotherapy drugs, particularly doxorubicin. In a large study of children treated through the National Wilms Tumor Studies, 4.4% of those who received doxorubicin at initial diagnosis developed heart failure within 20 years. That risk jumped to 17.4% for those who received it during treatment for relapsed disease. Girls face a higher risk than boys (about 4.5 times higher), and the risk increases with higher total doses and with radiation to the chest or left side of the abdomen. Even among survivors without obvious heart symptoms, about 25% showed subtle signs of heart muscle strain on testing.
Kidney function requires lifelong attention, especially since most survivors are living with a single kidney. For children with standard unilateral disease and no underlying genetic conditions, the risk of severe kidney failure within 20 years is low, around 0.6%. But for children with bilateral disease, that number rises to 12%. Children with Denys-Drash syndrome face a 74% risk of kidney failure, and those with WAGR syndrome face a 36% risk. Even survivors with good overall kidney function often show subtle signs of reduced filtering capacity, with chronic kidney insufficiency reported in 19% to 73% of survivors depending on the study and how it was measured.
Survivors also carry a small but real increased risk of developing a second, unrelated cancer later in life, particularly if they received radiation therapy. Musculoskeletal effects, including uneven growth of the spine or soft tissues in the area that received radiation, can develop during the growth years. Reproductive health may also be affected, depending on the specific treatments used. For all of these reasons, Wilms tumor survivors benefit from structured long-term follow-up programs that track heart, kidney, and overall health through adolescence and beyond.