eMedicine Specialties > Urology > Cancer, Wilms Tumor and Neuroblastoma

Wilms Tumor

Author: Marc Cendron, MD, Associate Professor of Surgery, Harvard School of Medicine; Consulting Staff, Department of Urological Surgery, Children's Hospital Boston
Contributor Information and Disclosures

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:

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.

More on Wilms Tumor

Overview: Wilms Tumor
Workup: Wilms Tumor
Treatment: Wilms Tumor
Follow-up: Wilms Tumor
References

References

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  2. Davies-Johns T, Chidel M, Macklis RM. The role of radiation therapy in the management of Wilms' tumor. Semin Urol Oncol. Feb 1999;17(1):46-54. [Medline].

  3. de Kraker J, Jones KP. Treatment of Wilms tumor: an international perspective. J Clin Oncol. May 1 2005;23(13):3156-7; author reply 3157-8. [Medline].

  4. Egeler RM, Wolff JE, Anderson RA, Coppes MJ. Long-term complications and post-treatment follow-up of patients with Wilms' tumor. Semin Urol Oncol. Feb 1999;17(1):55-61. [Medline].

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  6. Green DM. The treatment of stages I-IV favorable histology Wilms' tumor. J Clin Oncol. Apr 15 2004;22(8):1366-72. [Medline].

  7. Levien MG, Bringelsen KA. Postoperative chemotherapy in the National Wilms' Tumor Studies. Semin Urol Oncol. Feb 1999;17(1):40-5. [Medline].

  8. Li W, Kessler P, Yeger H, Alami J, Reeve AE, Heathcott R. A gene expression signature for relapse of primary wilms tumors. Cancer Res. Apr 1 2005;65(7):2592-601. [Medline].

  9. Metzger ML, Dome JS. Current therapy for Wilms' tumor. Oncologist. Nov-Dec 2005;10(10):815-26. [Medline].

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  12. Vujanic GM, Sandstedt B, Harms D, Kelsey A, Leuschner I, de Kraker J. Revised International Society of Paediatric Oncology (SIOP) working classification of renal tumors of childhood. Med Pediatr Oncol. Feb 2002;38(2):79-82. [Medline].

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

Contributor Information and Disclosures

Author

Marc Cendron, MD, Associate Professor of Surgery, Harvard School of Medicine; Consulting Staff, Department of Urological Surgery, Children's Hospital Boston
Marc Cendron, MD is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, European Society for Paediatric Urology, Johns Hopkins Medical and Surgical Association, New Hampshire Medical Society, Society for Fetal Urology, and Society for Pediatric Urology
Disclosure: Nothing to disclose.

Medical Editor

Leonard Gabriel Gomella, MD, FACS, The Bernard W Godwin Professor of Prostate Cancer Chairman, Department of Urology, Associate Director of Clinical Affairs, Kimmel Cancer Center, Thomas Jefferson University
Leonard Gabriel Gomella, MD, FACS is a member of the following medical societies: American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Laser Medicine and Surgery, American Urological Association, Sigma Xi, Society for Basic Urologic Research, Society of University Urologists, and Society of Urologic Oncology
Disclosure: GSK Consulting fee Consulting; Astra Zeneca Honoraria Speaking and teaching; Watson Pharmaceuticals Consulting fee Consulting

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Dan Theodorescu, MD, PhD, Paul Mellon Professor of Urologic Oncology, Department of Urology, University of Virginia Health Sciences Center
Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Terumo Corporation Consulting fee Consulting; Omeros Corporation Consulting fee Consulting

Chief Editor

Bradley Fields Schwartz, DO, FACS, Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine
Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Nothing to disclose.

 
 
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