Wilms' tumor
Wilms' tumor, also known as nephroblastoma, is a type of kidney cancer primarily affecting children, making it the most common renal tumor in this age group. It typically arises within the first five years of life, peaking around ages three and four, and usually affects one kidney. In the United States, about 1 in 10,000 children are diagnosed with this condition. The tumor can be classified into favorable and unfavorable types based on microscopic appearance, influencing treatment approaches and outcomes. While the overall five-year survival rate is around 92%, outcomes can vary based on disease stage at diagnosis, tumor characteristics, and patient age.
Risk factors for developing Wilms' tumor include a family history of the disease and specific congenital abnormalities, such as WAGR syndrome and Beckwith-Wiedemann syndrome. Symptoms often include an abdominal mass, stomach pain, blood in urine, and other systemic signs. Diagnosis typically involves imaging tests and possibly biopsy. Treatment generally involves nephrectomy and chemotherapy, with the approach tailored to the specifics of each case. Regular screening is advised for children with known risk factors to facilitate early detection and intervention.
Wilms' tumor
ALSO KNOWN AS: Nephroblastoma; kidney tumor
DEFINITION: Wilms tumor is a type of kidney cancer that predominantly affects children. It is the most common renal tumor of childhood. It usually occurs in the first five years of life, especially around ages three and four. In most cases, Wilms tumor affects only one of the two kidneys. In the United States, the frequency of this tumor is 1 in 10,000 children.
Wilms tumor is generally divided into two types based on how it looks under the microscope. Favorable types of Wilms tumor generally have a better outcome and require less aggressive treatment. The unfavorable or anaplastic histology of Wilms tumor is still curable but requires more aggressive chemotherapy and higher doses of radiation therapy. Despite the more aggressive therapies, survival is generally more limited. However, the overall five-year survival rate for Wilms tumor is 92 percent, varying according to the stage of disease at diagnosis, tumor size, histopathologic features (with worse outcomes for diffuse anaplasia), and age.
Risk Factors
One likely risk factor for Wilms tumor is having a family member with a Wilms tumor; approximately 1 to 2 percent of patients have one or more relatives with a history of Wilms tumor. Certain birth defects also increase the risk of a Wilms tumor. These include WAGR, a syndrome that includes Wilms tumor; aniridia—a completely or partially missing iris (colored part) of the eyes; genitourinary abnormalities, such as defects of the kidneys, urinary tract, penis, scrotum, testicles, clitoris, or ovaries; and mental retardation.
Additional risk factors include Beckwith-Wiedemann syndrome, in which patients have a larger than normal tongue, larger than normal internal organs, and one arm or leg that may be larger than the other; Denys-Drash syndrome, which is the absence of the penis, scrotum, and testicles; Perlman syndrome, which is characterized by fetal gigantism, renal dysplasia, and multiple congenital abnormalities; and hemihypertrophy, in which one side of the body is larger than the other. Other genetic defects, including defects on chromosome 11, also increase risk. A persistence of nephrogenic rests (embryonic tissue that is retained in the kidney) beyond early childhood is also a risk factor for Wilms tumor. Patients with these abnormalities should be regularly screened for Wilms tumor during childhood.
Etiology and Genetics
The great majority of cases of Wilms tumor are sporadic (nonfamilial), and they are believed to arise as the result of genetic mutations in the kidney tissue either before or shortly after birth. Less than 5 percent of all cases are inherited, and even among these it appears that mutations in any of several different genes may be responsible. About one-third of patients with familial Wilms tumor have mutations in the WT1 gene, located on the short arm of chromosome 11 at position 11p13. The protein encoded by this gene is a regulatory molecule that acts to turn other genes on at appropriate times during the development of kidney and reproductive tissue. Failure to do so as a result of mutations in the WT1 gene may result in the uncontrolled growth of kidney tumors characteristic of the disease.
Other genes known to be associated with genetic predisposition to Wilms tumor include WT2 (at position 11p15.5) and WTX (on the X chromosome). Other genes and chromosomes that may be involved in Wilms tumor include chromosomes 16q and 1p, gene CACNA1E (at position 1q25.3), genes MEOX2 and SOSTDC1 (at position 7p21), SKCG-1 (at position 11q23.2), TP53 gene, FBXW7 gene, and MYCN gene. A small percentage of patients with Wilms tumor have identifiable genetic syndromes in which this malignancy is one manifestation of a larger panoply of clinical presentations. These include Denys-Drash syndrome, Beckwith-Wiedemann syndrome, Perlman syndrome, and WAGR syndrome.
The inheritance of familial Wilms tumor follows a classic autosomal dominant pattern, meaning that a single copy of the mutation is sufficient to cause full expression of the disease. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children. In some cases, however, the disease results from a spontaneous new mutation, so in these instances, affected individuals will have unaffected parents. Curiously, it has been shown that at the molecular level within cells, both copies of the WT1 gene must be mutated in order to initiate the formation of kidney tumors. One of these mutations is the inherited one that is present in all cells, while the second occurs randomly during normal cell growth in kidney tissue. It is this acquired second mutation that triggers tumor formation in the affected tissue.
Symptoms
The first noticeable symptom is usually a large lump or hard mass in the abdomen. Other symptoms may include stomach pain, fever, blood in the urine (hematuria), high blood pressure, loss of appetite, weight loss, nausea, vomiting, and constipation. Erythrocytosis (a condition where there are too many red cells in the blood) may also be a presenting sign that the doctor finds when taking a blood test. This is because Wilms tumor makes a protein that causes increased production of red cells. Wilms tumors may grow larger without causing any pain or other symptoms. In advanced stages, metastasis may occur, with the most common metastatic sites including the lungs, liver, and lymph nodes. Less commonly, metastasis to the brain and bones may also occur.
Screening and Diagnosis
The doctor will ask about a child’s symptoms and medical history and will perform a physical exam. Blood and urine tests may be done. The child will need one or more tests in order to look for tumors. These tests provide pictures of the kidney, surrounding blood vessels, and other organs to which the cancer may have spread.
These tests include ultrasound, a test that uses sound waves to examine the kidneys. A computed tomography (CT) scan, a type of x-ray that uses a computer to make pictures of the inside of the body, may also be done. In some CT scans, a dye is first injected into a vein. This dye makes structures in the body more visible on an x-ray. Additional tests include a functional magnetic resonance imaging (fMRI) scan, a test that uses magnetic waves to make pictures of the inside of the body; a chest x-ray, a test that uses radiation to look for the spread of cancer to the lungs; a bone scan, in which a small amount of a radioactive material is injected into a vein to highlight any cancer that may have spread to the bones; and a biopsy, the removal of a sample of tissue to test for cancer cells. In Wilms tumor, the biopsy may actually be a major surgical procedure to remove the kidney.
Except for removal of the kidney, these tests are not invasive but require the child to remain still. Sedation may be needed.
Children who have risk factors for Wilms tumor should have a physical exam with a specialist and an ultrasound every three months until age six or seven. This screening should be done even if they do not have symptoms. It can help find tumors while they are small and have not yet spread to other parts of the body.
Treatment and Therapy
Wilms tumor can be cured in most children. The specific treatment depends on if the cancer has spread beyond the kidney to other parts of the body and, if so, how far. The process for determining this, called staging, uses the results of the diagnostic tests. Tumor size, cell type, whether the tumor is favorable or unfavorable, and the child’s age and health are also considered in choosing treatment. The National Wilms Tumor Study Group and the Children's Oncology Group recommend nephrectomy (removal of part or all of a kidney), followed by chemotherapy with or without radiation therapy.
Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy can be given in many forms, including pills, injections, and via a catheter placed in a blood vessel. The drugs enter the bloodstream and travel through the body, killing mostly cancer cells but also some healthy cells.
Radiation therapy is the use of radiation to kill cancer cells and shrink tumors. Radiation may be external radiation therapy, in which radiation is directed at the tumor from a source outside the body.
Prevention and Outcomes
Currently, there is no known way to prevent the majority of cases of Wilms tumor. Genetic counseling is recommended for pregnancies at risk for inheriting the WT1 gene or 11p15 genomic alteration, including prenatal testing of the fetus or preimplantation genetic testing for embryos created by in vitro fertilization.
Bibliography
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Kalapurakol, John A., and Patrick R. M. Thomas. “Wilms’ Tumor.” Perez and Brady’s Principles and Practice of Radiation Oncology. Ed. Edward C. Halperin, Carlos A. Perez, and Luther W. Brady. Philadelphia: Wolters, 2008. Print.
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Pritchard, Jones, Kathy, et al. "Omission of Doxorubicin from the Treatment of Stage II–III, Intermediate-Risk Wilms' Tumour (SIOP WT 2001): An Open-Label, Non-Inferiority, Randomised Controlled Trial." Lancet 386.999 (2015): 1156–64. PDF file.
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