• Clinical science

Wilms tumor (Nephroblastoma)

Summary

Wilms tumor (nephroblastoma) is the most common renal malignancy in children, typically affecting children 2–5 years of age. A minority of cases are associated with specific syndromes (e.g., WAGR, Beckwith-Wiedemann) and gene mutations (e.g., WT1). Wilms tumor is typically an incidental finding that manifests as a large abdominal mass. Other signs and symptoms may occur, such as hematuria and abdominal pain, especially in tumors that are large, ruptured, or metastasized. Treatment consists of tumor resection and chemotherapy for all stages (except for very low-risk tumors), while radiation is also used in advanced disease.

Epidemiology

  • Peak incidence: 2–5 years
  • Most common malignant neoplasm of the kidney in children

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

The exact etiology of Wilms tumor remains unknown; , but it is associated with several genetic mutations and syndromes.

Genetic predisposition

  • Gene mutations have been found in children both with and without genetic syndromes who have Wilms tumor.
  • The WT1 (Wilms tumor 1) gene; is the most important Wilms tumor gene (mutated in ∼ 10–20% of cases)

Associated syndromes

WAGR syndrome consists of Wilms tumor, Aniridia, Genitourinary (GU) anomalies, and intellectual disability (mental Retardation)! Denys-Drash syndrome is a mild form of WAGR without aniridia or mental retardation.

References:[1][2][3][4][5][6][7][8]

Clinical features

  • Abdominal mass (often found incidentally!)
    • Non-tender
    • Unilateral, not crossing midline (however, up to 10% of cases are bilateral and/or multifocal)
    • Smooth and firm
  • Other signs and symptoms

Wilms tumor should be suspected in a toddler with a non-tender abdominal mass, especially if it is firm, smooth, and associated with hematuria and/or hypertension!

References:[9][1]

Diagnostics

  • Urinalysis: hematuria may be present
  • Imaging
    • Best initial test: ultrasound
      • Hypervascular tumor
      • Mostly uniform echogenicity with hypoechoic areas of necrosis
    • Abdominal CT/MRI: assess extent of involvement and help with surgical planning
    • CT thorax/CXR: determine metastases and staging

Biopsy is usually reserved for assessing nodules that are suspected metastases, as tumor capsule rupture and spillage results in more advanced staging and intensive treatment!

References:[9][1][10]

Pathology

Wilms tumor consists of embryonic glomerular structures and may include cysts, hemorrhage, or necrosis. It typically has a pseudocapsule. Classically it is made up of three different cell types, though some tumors may have two or just one of these types.

References:[1]

Differential diagnoses

Diagnostic consideration Wilms Tumor Neuroblastoma
Clinical findings: fever and weight loss Less common More common
CT/MRI findings of calcifications, vascular encasement, and/or midline crossing Less common More common
I123-MIBG scan (scintigraphy) Negative Positive (∼ 90% of cases)
Catecholamine metabolites in urine (VMA = vanillylmandelic acid, HVA = homovanillic acid) Negative Positive (∼ 70–90% of cases)
  • Other renal tumors found in children (e.g., clear cell sarcoma)

References:[11]

The differential diagnoses listed here are not exhaustive.

Treatment

Treatment Stages I and II Stages III and IV Stage V (Bilateral)

Nephrectomy

X

X

Dactinomycin and vincristine

X

X

X

Doxorubicin

X

X

Radiation

X

X

Preoperative chemotherapy

X

Renal parenchymal-sparing resection

X

References:[12]

Prognosis

  • Good prognosis: five-year survival rates up to 90%

References:[12]

Prevention

  • Regular screening (primary prevention) of children with associated syndromes, including WAGR, Beckwith-Wiedemann, and Denys-Drash (e.g., abdominal ultrasound every three months until the age of 8)
  • The majority of tumor recurrences happen within two years of treatment.

References:[12][1]