eMedicine Specialties > Urology > Cancer, Wilms Tumor and Neuroblastoma
Wilms Tumor
Updated: May 5, 2009
Introduction
Wilms tumor (WT) is the fifth most common pediatric malignancy and the most common type of renal tumor in children. The treatment used to treat Wilms tumor is an example of success achieved through a multidisciplinary collaboration of the National Wilms' Tumor Study Group (NWTSG) and the Societe Internationale d'Oncologie Pediatrique (SIOP).
History of the Procedure
Fifty years ago, with surgery alone, the survival rate 2 years after nephrectomy was 20%. The introduction of adjuvant radiotherapy raised the survival rate to 50% overall. Owing to the cooperative efforts of oncologists, surgeons, and pathologists and with the introduction of chemotherapy with vincristine, dactinomycin (actinomycin D), and doxorubicin, the overall survival rate has risen to 90% in the last 30 years.
Frequency
The incidence of Wilms tumor is approximately 0.8 cases per 100,000 persons. Approximately 500 new cases are diagnosed each year in the United States, with 6% involving both kidneys.
Etiology
Wilms tumor may arise in 3 clinical settings, the study of which resulted in the discovery of the genetic abnormalities that lead to the disease. Wilms tumors can arise sporadically, can develop in association with genetic syndromes, or can be familial. Although some of the molecular biology of Wilms tumor is coming to light, the exact cellular mechanisms involved in the etiology of the tumor are still being investigated.
Sporadic Wilms tumor
Most cases of Wilms tumor are not part of a genetic malformation syndrome and occur in the absence of a family history of the malignancy; however, familial Wilms tumor is very common in certain families. Genetic syndromes that predispose to and may include Wilms tumor include the following:
- Beckwith-Wiedemann syndrome (macroglossia, gigantism, and umbilical hernia)
- Hemihypertrophy
- Congenital aniridia
- Wilms tumor, aniridia, genitourinary malformations, and mental retardation (WAGR syndrome)
- Denys-Drash syndrome (Wilms tumor, pseudohermaphroditism, and glomerulopathy)
- Trisomy 18 mutation
These clinical observations have led to genetic and molecular studies that have enhanced discovery of the genetic mechanism that promotes Wilms tumor genesis. In addition, the molecular genetic characterization of Wilms tumor plays a major role in the understanding of the genetic aspects of carcinogenesis in general.
Molecular genetics
Based on the model developed originally for retinoblastoma, Knudson and Strong proposed that Wilms tumor results from 2 mutational events based on loss of function of tumor suppressor genes.
The first mutation, the inactivation of the first allele of the specific tumor suppressor gene, involves prezygotic and postzygotic aspects. Prezygotic (constitutional or germline) mutations are inherited or result from a de novo germline mutation. This mutation is present in all body cells and predisposes the patient to familial and/or multiple Wilms tumor. Postzygotic mutations occur only in specific cells, and they predispose to single tumors and sporadic cases of Wilms tumor.
The second mutation is inactivation of the second allele of the specific tumor suppressor gene.
Although the model of the retinoblastoma suppressor gene has been used to explain the genetics, clinical characteristics of Wilms tumor suggest that the molecular genetic mechanism in the second type of mutation depends on more than one tumor suppressor gene.
The WT1 gene (at chromosome 11p13) is a tissue-specific gene for renal blastemal cells and glomerular epithelium, with both renal precursor cells thought to harbor sites of origin of Wilms tumor. The expression of WT1 peaks around birth. As the kidney matures, the expression declines. It is also a dominant oncogene; hence, a certain mutation in only 1 of the 2 alleles is enough to promote changes that may lead to the formation of Wilms tumor. The WT2 gene (at chromosome 11p15) remains isolated.
In addition, several genetic factors have been identified as possible prognostic factors in individuals with Wilms tumor. One such factor is loss of heterozygosity at chromosomes 1p and 16q. Children with loss of heterozygosity at 16q appear to be at greater risk of relapse and mortality than children without this genetic change. According to the latest NWTS-5 study, tumor-specific loss of heterozygosity for both chromosomes 1p and 16q, identified in about 5% of patients with favorable-histology Wilms tumor, was shown to be associated with a significantly increased risk of relapse and death.
Pathophysiology
The pathophysiology of Wilms tumor is characterized by an abnormal proliferation of the metanephric blastema cells, which are believed to be primitive embryologic cells of the kidney.
Presentation
Wilms tumor is diagnosed at a mean age of 3.5 years. The most common feature at presentation is an abdominal mass. Abdominal pain occurs in 30%-40% of cases. Other signs and symptoms of Wilms tumor include hypertension, fever caused by tumor necrosis, hematuria, and anemia.
Major congenital anomalies include genitourinary anomalies (WAGR and Denys-Drash syndromes, 5% of cases), ectopic solitary horseshoe kidney, hypospadias and cryptorchidism, hemihypertrophy and organomegaly (Beckwith-Wiedemann syndrome, 2% of cases); and aniridia (1% of cases). Children with such syndrome anomalies should undergo periodic testing for Wilms tumor. Ultrasonography of the kidneys (once or twice per year) is a good screening tool.
Indications
Indications for primary surgical excision of a Wilms tumor (WT) include tumors confined to the kidney, extending beyond the kidney but not crossing the midline, and with or without vascular extension. Postchemotherapy excision of the tumor is indicated in patients with bilateral tumors, tumors that extended beyond the midline and have shrunk, and tumors with vascular extension. Surgery alone is not recommended for Wilms tumor based on the results of the NWTS-5 study.
Relevant Anatomy
Wilms tumor (WT) arises from the primitive embryonal renal tissue. Grossly, Wilms tumor is typically an intrarenal solid or cystic mass, which may displace and, in rare cases, invade the renal collecting system. The tumor extends into the renal vein in 40% of cases. In very rare cases, it extends into the ureter and down to the bladder, where it may cause hematuria. Wilms tumor is bilateral in 6% of cases. Local invasion is rare and tumor spread is usually through lymphatic and vascular routes.
Contraindications
Contraindications to primary surgery for Wilms tumor (WT) include bilateral tumors and documented metastatic disease. Large tumors that extend beyond the midline, have vascular extension, or both are relative contraindications since some surgeons elect to obtain tissue via surgical excision, but this may expose patients to increased surgical risks.
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References
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Further Reading
Keywords
Wilms tumor, nephroblastoma, WT, embryoma of the kidney, mixed tumor of the kidney, sporadic Wilms tumor, familial Wilms tumor, bilateral Wilms tumor, Beckwith-Wiedemann syndrome, hemihypertrophy, congenital aniridia, WAGR syndrome, Denys-Drash syndrome, trisomy 18 mutation, teratoid Wilms tumor
