MD2B - Pediatric Oncology: Wilms Tumor

Overview

Wilms tumor, also known as nephroblastoma, is a solid tumor that arises from immature kidney cells. It is the fourth most common type of pediatric cancer and the most common abdominal cancer in children, with approximately 500 new cases diagnosed annually. Wilms tumor typically occurs around age  3 and is rarely seen after age 8. It usually affects only one kidney, but in 5% of cases can affect both kidneys. The overall five-year survival rate for children with Wilms tumor exceeds 90%. Prognosis depends on factors such as cancer stage (how far the cancer has spread), histopathologic features (what the cancer cells look like under the microscope), patient age, and tumor size.

Risk Factors

Females have a higher risk than males of both unilateral and bilateral tumors. Maternal use of hair dyes and paternal occupational exposures as a welder or machinist have been associated with higher rates of Wilms. About a third of Wilms tumors are positive for inactivation of the WTX gene on chromosome X, though the function of this gene in normal development is poorly understood. 

In approximately 10% of cases, Wilms tumor arises as part of a congenital malformation syndrome. WAGR syndrome results from a mutation at chromosome 11p and is characterized by Wilms tumor, aniridia (absence of the iris of the eye), genitourinary malformations, and intellectual disability. Denys-Drash Syndrome also called by a mutation at 11p, involves a combination of Wilms tumor, renal disease, and pseudo-hermaphroditism (where genitalia are of one sex, but some physical characteristics of the opposite sex are present ). In Beckwith-Wiedemann Syndrome, children present with macroglossia (enlarged tongue), omphalocele (abdominal organs outside of the body), Wilms tumor, and visceromegaly (large organs). Wilms tumor has also been reported in association with Bloom Syndrome, Fanconi anemia, and Li-Fraumeni syndrome.

Symptoms

Most Wilms tumors are found after they have grown quite large, as these tumors can develop without causing pain or noticeable symptoms.  Fortunately, they are typically discovered before metastasis occurs. The most common sign is abdominal swelling often noticed by parents when bathing or dressing the child, as they feel a firm mass in the belly. The tumor is not usually painful. Less common symptoms of Wilms tumor include abdominal pain, fever, hematuria (blood in the urine), nausea, vomiting, changes in weight or bowel movements, and high blood pressure, which may be detected by a pediatrician due to elevated levels of renin in the blood.

Diagnosis

The child's physician will perform a physical examination, schedule imaging tests, and order laboratory tests to help determine if the child has Wilms tumor and to aid in developing the appropriate treatment plan.

Imaging tests

• Ultrasound (sonography): A diagnostic imaging test that uses high-frequency sound waves to create images of blood vessels and internal structures. It can determine whether a mass is cystic or solid and can often distinguish benign from malignant tumors. This is usually the first imaging study to be done because it is painless and noninvasive.
• Computed Tomography (CT or CAT) Scan: A diagnostic imaging procedure that combines X-rays and computer technology to produce cross-sectional images of the body, often used to visualize soft tissues. It can often visualize tumor spread into adjacent organs and the presence of tumor in the opposite kidney. Often, contrast dye is given to aid in tissue visualization.
• Magnetic Resonance Imaging (MRI): A diagnostic imaging procedure that uses large magnets, radio frequencies, and a computer to generate detailed images of internal structures. It can visualize cancer invasion into major blood vessels surrounding the kidney.
• Additional tests such as a chest x-ray, chest CT, radionucleotide bone scan, x-ray skeletal surveys or brain MRI  may be performed to detect metastatic (distant) spread of cancer.

Lab tests

• CBC (complete blood count) with differential: A blood sample is taken to assess the number and shape of various blood cells, including red blood cells, white blood cells, and platelets.
• Blood Chemistry Panel: A blood sample is analyzed to evaluate kidney and liver function. Calcium levels can also aid in diagnosis.
• Urinalysis: A urine test detects the presence of blood or catecholamines (which would suggest a diagnosis of neuroblastoma, rather than Wilms tumor)

Staging and Prognosis

The tumor is staged based on physical examination, imaging studies, laboratory tests, and biopsy results (if completed). Staging is based on the National Wilms’ Tumor Study (NWTS) staging categories:

Stage 1: Tumor is confined to only one kidney and can be completely removed by surgery

Stage 2: Tumor extends beyond the kidney but can be completely removed by surgery

Stage 3: Tumor has spread slightly beyond the kidney (but not outside of the abdomen and pelvis) and cannot be completely removed by surgery

Stage 4: The cancer has spread outside the abdomen and pelvis to other organs in the body such as the lungs, liver, bone, or brain

Stage 5: Cancer is present in both kidneys

Important prognostic factors present at the time of diagnosis include age >24 months, larger size of the tumor, lymph node involvement, metastases at time of diagnosis, and appearance of the cancer cells.

Treatment

Treatment of Wilms tumor involves the combination of surgery, chemotherapy, and possibly radiation. Due to advances in the treatment of Wilms tumor, the overall success rate in curing this type of cancer is around 90%.

Surgery

Surgical removal is the primary method for achieving local control of Wilms tumor. A surgeon will perform a nephrectomy, which may involve removing part of the kidney, the entire kidney, or the kidney along with surrounding tissue, depending on the tumor's location and extent at the time of diagnosis. Surgery is often combined with adjuvant chemotherapy or radiotherapy, especially in cases where there is an increased risk of recurrence.

Chemotherapy

Chemotherapy is a systemic treatment for Wilms tumor and is typically administered preoperatively. It travels through the bloodstream targeting cancer cells throughout the body, including those that may have spread beyond the kidney. Early-stage tumors may be treated with actinomycin-D and vincristine, while later-stage tumors require combinations of three or more drugs. Side effects of chemotherapy include nausea, vomiting, mouth sores, change in bowel habits, hair loss, increased risk of infection, fatigue, and bruising.

Radiation

Radiation uses high-energy x-rays to kill cancer cells. Radiation is used in the more advanced stages of Wilms tumor. Only a quarter of Wilms patients are treated with radiation, and it is typically started postoperatively along with concurrent chemotherapy. Side effects of radiation include nausea, diarrhea, fatigue, and skin changes.