Wilms' Tumor

Background

Wilms tumor is an intrarenal tumor of neoplastic embryonal renal cells of the metanephros.  

  • Most common malignant renal tumor of childhood (6% of all childhood cancers)
  • 450 to 500 cases of Wilms tumor diagnosed in the United States annually (an incidence of 8 cases per million in children under 15 years of age)
  • Median age at diagnosis of Wilms tumor is about 3 years of age, with earlier diagnosis occurring in bilateral tumors. The incidence of bilateral tumors is 7%.
  • 2/3 of cases are diagnosed before the age of 5 and 95% of cases before the age of 10
  • Occurs with equal frequency in males and females, with a slightly higher incidence of disease in African American children than in Caucasian and Asian children
  • Most develop sporadically, 10% of cases are associated with recognized syndromes

 

Common Symptoms

  1. Abdominal or flank mass, may be unilateral or bilateral, generally smooth and firm
  2. Typically asymptomatic, may cause abdominal pain, found in nearly half of patients, due to hemorrhage into the tumor or invasion of the renal pelvis
  3. Hematuria, often microscopic
  4. Hypertension, found in up to 25% of patients at presentation. Possible etiologies include: renin production by the tumor, renal ischemia secondary to invasion into the renal artery, or intraparenchymal AV fistula formation.

 

Diagnosis

When an abdominal mass is discovered, the initial imaging modality of choice is ultrasound.

  • Essential prior to treatment to accurately localize the source of the mass, identify any genitourinary abnormalities that may co-exist, and to examine the contralateral kidney.
  • Intrarenal masses are suggestive of Wilms tumor; extrarenal masses suggest another cause, such as a neuroblastoma.

CT is often the next imaging modality of choice, which can confirm the location and extent of the tumor, assess the vena cava, and evaluate the contralateral kidney.

220px--Wilms_Tumor_CTScan.ogv_.jpg
CT scan of 11 cm Wilms' tumor of right kidney in 13-month-old. https://en.wikipedia.org/wiki/Wilms%27_tumor

Chest radiograph is also performed in order to rule out pulmonary metastases, as up to 15% of patients will have pulmonary metastases at the time of diagnosis.

Differential Diagnosis Abdominal/Pelvic Tumors

  • Neuroblastoma: will usually have increased urinary metanephrines (VMA, HVA)
  • NHL: Increased LDH, bone marrow infiltration
  • Rhabdomyosarcoma: present in a wider range of ages, can affect the urogenital system and may present with vaginal bleeding or paratesticular mass
  • Germ Cell Tumor: increased serum beta hcg and/or AFP
  • Hepatoblastoma/Hepatoma: increased serum AFP
  • Other Renal Tumors: mesoblastic nephroma (neonates), clear cell sarcoma, rhabdoid tumor, renal cell carcinoma

Staging

  • Stage 1: Limited to the kidney
  • Stage 2: Extension into the renal sinus but complete excision is possible
  • Stage 3: Residual abdominal disease following excision
  • Stage 4: Distant metastasis to the lung or liver
    • Sites of Metastasis: Abdominal lymph nodes, asymptomatic parenchymal lung leions and liver nodules

450px-Wilms_tumor_0.jpg
Cut section showing two halves of a nephroblastoma specimen. Note the prominent septa subdividing the sectioned surface and the protrusion of tumor into the renal pelvis, resembling botryoid rhabdomyosarcoma. https://en.wikipedia.org/wiki/Wilms%27_tumor

 

Prognosis

  • 5 year survival: 90%
  • Continued screening for pulmonary spread by serial chest CT and for development in the contralateral kidney by serial ultrasound

 

Associated Anomalies

Wilms tumor is associated with a number of congenital anomalies and syndromes:

  1. WAGR syndrome — Wilms tumor, Aniridia, Genital anomalies, and intellectual disability (formerly known as mental retardation). This syndrome is associated with a constitutional deletion on chromosome 11 (del 11p13 — the WT1 locus), and the incidence of Wilms tumor in this syndrome is over 40%.
  2. Beckwith-Weideman syndrome — an overgrowth syndrome characterized by excess growth at the cellular, tissue and organ levels. It is associated with organomegaly, macroglossia, hypoglycemia, omphalocele and hemihypertrophy. Beckwith-Weideman syndrome is caused by a change in the gene locus at band p15.5 on chromosome 11 — the WT2 locus. The risk of Wilms tumor with Beckwith-Weideman syndrome is from 10 to 20%.
  3. Denys-Drash syndrome — a very rare syndrome of male pseudohermaphroditism (or genitourinary abnormalities), renal mesangial sclerosis and Wilms tumor. The genetic abnormality in these infants also maps to chromosome 11, p13, but it is a dominant negative, missense mutation.
  4. Aniridia — children with sporadic aniridia are at risk for Wilms tumor. The incidence of aniridia in patients with Wilms tumor is 1.1%.
  5. Children with horseshoe kidney are at twice the risk of developing Wilms tumor when compared to the general population.

 

Screening Recommendations

  • Children diagnosised with Beckwith-Wiedemann or WAGR syndromes
  • Unaffectd kidney of children with previously diagnosed unilateral tumor (1.5% of children diagnosed with Wilms' before the age of one will develop a second tumor in the remaining unaffected kidney)

 

References

  1. Aune, Gregory J. Wilms tumor. Pediatrics in Review 29.4 (2008): 142-143.
  2. Cotton, Cecilia A. et al. Early and Late Mortality After Diagnosis of Wilms Tumor. J. Clin. Oncol. (2009) 27(8): 1304-1309.
  3. Coppes, Max J. et al. Factors Affecting the Risk of Contralateral Wilms Tumor Development: A Report From the National Wilms Tumor Study Group. Cancer (1999) 85:1616-1625.
  4. D'angio, Giulio J., et al. Treatment of Wilms' tumor. Results of the third national Wilms' tumor study. Cancer 64.2 (1989): 349-360.
  5. Friedman, Alan. Wilms tumor. Pediatrics in Review/American Academy of Pediatrics (2013) 34: 328-30.
  6. Gommersall, Lyndon M. et al. Current Challenges in Wilms' Tumor Management. Nature Clinical Practice Oncology (2005) 2:298-304. 
  7. Kalapurakal, John A., et al. Management of Wilms' tumour: current practice and future goals. The Lancet Oncology 5.1 (2004): 37-46.
  8. Perlman, Elizabeth J. Pediatric renal tumors: practical updates for the pathologist. Pediatric and Developmental Pathology 8.3 (2005): 320-338.
  9. Ricafort, Rosanna. Tumor Markers in Infancy and Childhood. Pediatrics in Review 32.7 (2011): 306-308.
  10. Ries, Lynn A.G., et al (eds). Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975-1995. National Cancer Institute, SEER Program (1999): NIH Pub. No. 99-4649.
  11. Scott, Richard H., et al. Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. Journal of medical genetics 43.9 (2006): 705-715.
  12. Scott, Richard H., et al. Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice. Archives of disease in childhood 91.12 (2006): 995-999.

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