• Clinical science

Wilms tumor (Nephroblastoma)

Abstract

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 has been associated with several genetic mutations and syndromes.

Genetic predisposition

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]

Stages

There are two staging systems for Wilms tumor:

  • National Wilms Tumor Study (NWTS) system: used in the U.S. and Canada, and based on surgical evaluation before chemotherapy
  • International Society of Pediatric Oncology, or Société Internationale d'Oncologie Pédiatrique (SIOP) system: used in Europe, and based on surgical evaluation after chemotherapy.

Staging according to the National Wilms Tumor Study (NWTS)

NWTS staging is used in the U.S. and Canada. It is based on surgical evaluation prior to chemotherapy. The first four stages are applicable to unilateral disease.

Stage Description
I
  • Tumor affecting kidney only
  • Resection complete, capsule intact, no renal sinus vessel involvement, no tumor tissue outside area of resection
  • No rupture or previous biopsy
  • Microscopic regional lymph node inspection consistent with Stage 1
I
  • Tumor extending beyond kidney, but resected without evidence of tumor outside area of resection
  • Penetration beyond the renal capsule, into soft tissue of the renal sinus, or blood vessels beyond renal parenchyma (but within resected specimen)
III
IV
V
  • Bilateral renal involvement (5–7% of patients); each side staged separately


References:[10][1][11]

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
  • Additional evaluation

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][12]

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)

References:[13]

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:[10]

Prognosis

  • Good prognosis: five-year survival rates up to 90%
    • Very low-risk tumors (stages I and II, patients < 2 years, tumor mass < 550 g, favorable histology): 98% five-year survival rate
    • Diffuse anaplastic (high-risk) tumor: four-year event-free survival approx. 83% for stage II, 65% for stage III, and 33% for stage IV

References:[10]

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:[10][1]