Wilms' tumor and cancer

ALSO KNOWN AS: Nephroblastoma, renal (kidney) embryoma

RELATED CONDITIONS: Clear cell carcinoma of the kidney, rhabdoid tumor of the kidney, neuroepithelial tumor of the kidney, cystic partially differentiated nephroblastoma, mesoblastic nephroma, renal carcinoma, Beckwith-Wiedemann syndrome, WAGR syndrome, Denys-Drash syndrome

DEFINITION: Wilms’ tumor is a solid tumor of the kidney that may spread to the lungs, liver, brain, bone, or lymph nodes. The majority of cases of Wilms’ tumor occur in children younger than five years old. Wilms’ tumors are categorized at the cellular level or histologically as tumors with either favorable histology or anaplastic histology. Wilms’ tumors with favorable histology are composed of the three types of cells normally found in the kidney and account for 90 percent of Wilms’ tumor cases. The remaining 10 percent of Wilms’ tumor cases have cells that are anaplastic, which are primitive or undifferentiated cells that have large, distorted nuclei. The anaplastic cells can be focal, meaning located in a distinct area, or diffuse throughout the tumor.

Risk factors: Wilms’ tumors usually occur in otherwise healthy children, although 10 percent of Wilms’ tumor cases occur in children with certain genetic and developmental abnormalities present at birth. These abnormalities are categorized as overgrowth or nonovergrowth syndromes. Overgrowth syndromes include Beckwith-Wiedemann syndrome, hemihypertrophy, Perlman syndrome, Sotos’ syndrome, and Simpson-Golabi-Behemel syndrome. Nonovergrowth syndromes include aniridia, trisomy 18, WAGR syndrome, Blooms’ syndrome, and Denys-Drash syndrome. Wilms’ tumors in both kidneys, called bilateral Wilms’ tumors, are more common in children with associated developmental abnormalities. Children with diffuse hyperplastic perilobar nephroblastomatosis, characterized by abnormal tissue growth on the outer part of one or both kidneys, are also at higher risk for Wilms’ tumor.

Etiology and the disease process: The exact cause of Wilms’ tumor is unknown, although the association of Wilms’ tumor with genetic and developmental abnormalities suggests that mutations in one or more genes may play a role. Several genetic markers are associated with Wilms’ tumorsWT1, CTNNB1, WTX, TP53, and MYNC gene alterations. Although genetic mutations are most likely involved with the development of Wilms’ tumor, only about 1 percent of patients have a family member with Wilms’ tumor.

Many Wilms’ tumors arise from nephrogenic rests, clusters of embryonic kidney precursor cells left over from development. These early building blocks of kidneys usually develop into the cells of a mature kidney, go dormant, or die off. Wilms’ tumor arises when the embryonic cells divide and grow out of control. Genetic mutations may cause nephrogenic rests to be abnormally retained.

Incidence: Approximately 500 cases of Wilms’ tumor are diagnosed in the United States annually. Most patients are children between one and five, and rates of Wilms’ tumors decrease with age. Adult cases (over sixteen) are rare and associated with a poor prognosis. Bilateral Wilms’ tumors in both kidneys diagnosed at the same time or at different times make up approximately 5 to 10 percent of Wilms’ tumor cases. Wilms’ tumor accounts for 90 percent of childhood renal tumors diagnosed each year and for about 5 percent of all childhood cancers.

Symptoms: Wilms’ tumors are typically not detected until they become large enough to be felt as a mass in the abdomen. However, most are found before they metastasize. Additional symptoms may include blood in the urine, unexplained fever, high blood pressure, constipation, reduced appetite, abdominal pain, and weight loss.

Screening and diagnosis: Unless a child is at risk for developing Wilms’ tumor, routine screenings are not typically done. Screening of a symptomatic child includes a physical exam; assessment of health history; blood tests to examine the number of blood cells, amount of hemoglobin, and the presence of certain substances improperly released by organs and tissues; urine tests to check for blood, bacteria, sugar, or proteins; liver function tests; renal function tests; and imaging tests to visualize the kidneys. The most common imaging test is an ultrasound, but computed (CT), (MRI), and X-rays may also be used.

If a mass in the kidney is detected through imaging, diagnosis is established through surgery rather than biopsy. Biopsies are avoided because they could rupture the tumor, causing the cancerous cells to spread outside of an otherwise contained area. If possible, the entire affected kidney is removed during surgery in a procedure called a nephrectomy. A pathologist examines the removed tissue to confirm the diagnosis of Wilms’ tumor and to assess the histology.

The imaging studies, surgery, and pathology report results determine the stage. Since stages are independent of histology type, they are reported together (for example, Stage I, favorable histology). The stages characterized by the Wilms’ Tumor Study Group are most commonly used:

• Stage I: Cancer is found in only one kidney and was completely removed by surgery. The kidney and tumor were intact before removal, and the tumor was not biopsied prior to surgery. There is no evidence that the cancer entered the blood vessels or the regions beyond where it was removed. The majority of patients are diagnosed with Stage I.
• Stage II: The tumor is completely removed; however, before it was removed, the cancer spread to tissues and structures within and near the kidney.
• Stage III: The cancer spread beyond the kidney to nearby and other structures in the abdomen. It could not be completely removed by surgery. The tumor may have broken open before or during surgery, was biopsied before surgery, or was removed in more than one piece.
• Stage IV: Cancer spread to distant structures such as lungs, liver, brain, bone, or distant lymph nodes.
• Stage V: The cancer is in both kidneys at the same time. Each kidney gets a separate stage rating.

Treatment and therapy: Treatment depends on the stage and histology of the Wilms’ tumor. In general, tumors with anaplastic histology require more aggressive treatments and tend to be more resistant to chemotherapy than those with favorable histology. Stages I and II involve a and removal of nearby lymph nodes, followed by adjuvant chemotherapy. A dual chemotherapy regimen of vincristine and dactinomycin is typically used.

Stages III and IV require a nephrectomy followed by combination chemotherapy (dactinomycin, vincristine, and doxorubicin, or dactinomycin and vincristine) with radiation. Depending on the size and location of the tumor, chemotherapy may be given before surgery to shrink the tumor.

Stage V involves the removal of the tumors in both kidneys while retaining kidney function (a partial nephrectomy). A in Stage V cases may be done preoperatively to determine the stage of the tumors in each kidney. Chemotherapy and radiation therapies are given based on the stages of the tumors in the kidneys.

Wilms’ tumor is so rare that patients should be treated by specialists with experience (pediatric oncologists, pediatric surgeons, and pediatric radiation oncologists) and should be considered for a clinical trial.

Prognosis, prevention, and outcomes: Prognosis is related to the stage of disease at diagnosis, histological features, tumor size, patient age, whether Wilms’ tumor is diagnosed for the first time or is recurrent, the presence of abnormal chromosomes or genes, and access to experts with Wilms’ tumor experience. The four-year overall survival rates of Stages I through IV with favorable histology range from 99 to 86 percent. Anaplastic histology is associated with a less favorable prognosis, ranging from 83 to 38 percent four-year overall survival rates for Stages I through IV. Anaplastic histology is also associated with a higher rate of relapse.

There are no known preventive measures in children who are otherwise healthy. Children with congenital abnormalities who have been treated for Wilms’ tumor, as well as those with other risk factors, should undergo ultrasound screening every three or four months until the age of eight.

Children who have been exposed to high-intensity radiation or chemotherapy treatments are at risk for developing a second neoplasm elsewhere in the body and congestive heart failure later in life. This is referred to the late effects of treatment for childhood cancer. Patients are candidates for a kidney transplant if they have been free of Wilms’ tumor for one to two years.

Bibliography

Leslie, Stephen W., et al. "Wilms Tumor." National Library of Medicine, 30 May 2023, www.ncbi.nlm.nih.gov/books/NBK442004. Accessed 20 July 2024.

Li, Kai, et al. "Prognostic Role of Primary Tumor Size in Wilms Tumor." Oncology Letters, vol. 27, no. 4, 2024, pp. 1-11. doi.org/10.3892/ol.2024.14297.

Nirgude, Snehal, et al. "Cancer Predisposition Signaling in Beckwith-Wiedemann Syndrome Drives Wilms Tumor Development." British Journal of Cancer, vol. 130, no. 4, 2024, pp. 638-650. doi.org/10.1038/s41416-023-02538-x.

Torban, Elena, and Paul Goodyer. "Wilms’ Tumor Gene 1: Lessons from the Interface Between Kidney Development and Cancer." American Journal of Physiology-Renal Physiology, vol. 326, no. 1, 2024, pp. F3-F19. doi.org/10.1152/ajprenal.00248.2.

Vujanić, Gordan M., and William Mifsud. "Anaplasia in Wilms Tumor: A Critical Review." Pediatric Blood & Cancer, vol. 71, no. 7, 2024. doi.org/10.1002/pbc.31000.

"What Are Wilms Tumors?" American Cancer Society, www.cancer.org/cancer/types/wilms-tumor/about/what-is-wilms-tumor.html. Accessed 20 July 2024.

"Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)–Health Professional Version." National Cancer Institute, 14 June 2024, www.cancer.gov/types/kidney/hp/wilms-treatment-pdq. Accessed 20 July 2024.

"Wilms Tumors." Cleveland Clinic, 13 June 2022, my.clevelandclinic.org/health/diseases/23259-wilms-tumor. Accessed 20 July 2024.

"Wilms Tumors." Mayo Clinic, 4 May 2024, www.mayoclinic.org/diseases-conditions/wilms-tumor/symptoms-causes/syc-20352655. Accessed 20 July 2024.