Nephroblastoma

Nephroblastoma (Wilms tumor) is the most common renal malignancy in children, typically affecting children between 2 and 5 years of age. A minority of cases are associated with specific syndromes (e.g., WAGR, Beckwith-Wiedemann) and gene mutations (e.g., WT1). Nephroblastoma 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 predominantly used in advanced disease.

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

References: ^[1]

Epidemiological data refers to the US, unless otherwise specified.

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

Genetic predisposition ^[2][3]

• Gene mutations have been found in children both with and without genetic syndromes who have nephroblastoma (Wilms tumor).
• Associated with loss of function mutations of tumor supressor genes on chromosome 11
  • The WT1 (Wilms tumor 1) gene is the most important nephroblastoma tumor gene (mutated in ∼ 10–20% of cases).
  • WT2 (Wilms tumor 2) gene ^[4]

Associated syndromes ^[5]

• WAGR syndrome: Deletion of the 11p13 band leads to the deletion of the WT1 gene and other genes, such as PAX6. ^[6]
  • Nephroblastoma
  • Aniridia
  • Genitourinary anomalies
    • Pseudohermaphroditism, undescended testes in males (due to gonadal dysgenesis)
    • Early-onset nephrotic syndrome
  • Range of intellectual disability
• Denys-Drash syndrome: point mutation in WT1 gene, which encodes a zinc finger transcription factor ^[7]
  • Nephroblastoma
  • Pseudohermaphroditism, undescended testes in males (due to gonadal dysgenesis)
  • Early-onset nephrotic syndrome caused by diffuse mesangial sclerosis
• Beckwith-Wiedemann syndrome: mutations of the WT2 gene

WAGR syndrome consists of Wilms tumor, Aniridia, Genitourinary anomalies, and Range of intellectual disability.

Denys-Drash syndrome is a mild form of WAGR without aniridia or intellectual disability.

Abdominal symptoms

• Palpable abdominal mass (often found incidentally)
  • Non-tender
  • Unilateral and large but not crossing midline
  • Smooth and firm
• Abdominal pain (∼ 40% of cases)

Other signs and symptoms

• Hematuria (∼ 25% of cases)
• Hypertension (∼ 25% of cases)
• In cases of subcapsular hemorrhage:
  • Anemia
  • Possibly fever
• Symptoms caused by metastatic spread (e.g., pulmonary symptoms)

Nephroblastoma 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.

Careless palpation of a nephroblastoma can result in rupture of the renal capsule and tumor spillage!

• Urinalysis: hematuria may be present
• Imaging
  • Ultrasound (best initial test)
    • Hypervascular tumor
    • Mostly uniform echogenicity with hypoechoic areas of necrosis
  • Abdominal CT/MRI
    • To assess extent of involvement
    • Surgical planning
  • CT thorax/CXR
    • To detect metastases
    • 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.

Overview

• Nephroblastoma consists of embryonic glomerular structures.
• May include cysts, hemorrhage, or necrosis
• Typically has a pseudocapsule

Histology

• Classic type: consists of three cell types
  • Epithelial cells (i.e., glomeruli and tubules)
  • Stromal cells
  • Undifferentiated blastemal cells of metanephric origin
• Anaplastic type
  • Contains multipolar polypoid mitotic figures
  • Marked hyperchromasia of nuclei

Neuroblastoma

Other renal tumors

• Clear cell sarcoma
• Rhabdoid tumor
• Congenital mesoblastic nephroma
• Renal cell carcinoma
• Renal medullary carcinoma

The differential diagnoses listed here are not exhaustive.

• Good prognosis: survival rates are > 90% ^[10]
• The majority of tumor recurrences happen within two years of treatment.

• Regular screening of children with associated syndromes (e.g., abdominal ultrasound every three months until the age of 8)