Nephroblastoma

• It is a malignant tumor of the developing kidney.
• It involves the embryonal cells in the kidney.
• It is the most common renal tumor in children.
• Also called Wilm’s tumor (WT).

• Peak age at diagnosis is between 3 years and 4 years
• Mean age at diagnosis is 3.5 years
• Most cases (80%) are diagnosed before 5 years of age
• No sex predilection
• Most cases are sporadic (not related to any hereditary or genetic tendency)
• Only about 2.5% are familial

The clinical settings include:

• Sporadic
• Familial

Associated with genetic syndromes (12-15%):

• Familial type is associated with genito-urinary abnormalities such as:
  • Hypospadias
  • Cryptorchidism
  • Ureteral duplication
  • Polycystic kidneys

The genetic syndromes that may be associated with WT include:

• Beckwith-Wiedemann syndrome
• Unilateral hemihypertrophy
• Aniridia

• The exact etiology is unknown.
• WT is sporadic in 95%; familial in 1-2%; bilateral in 5-10%
• 2% of WT is associated with syndromes:
  • WAGR syndrome (WT, Aniridia, Genitourinary malformation, Mental Retardation)
  • Beckwith-Wiedemann syndrome (BWS) (Omphalocele, Macroglossia, Visceromegaly, and embryonal cell tumor)
  • Denys-Drash syndrome (WT, Intersex disorder, Nephropathy)
  • Perlman syndrome (Overgrowth syndrome with mental retardation)
• Other associated anomalies seen in WT include isolated hemihypertrophy, hypospadias, and undescended testes.
• Children with such syndromes should be screened with ultrasound every 6 months until 8 years of age.

Genes involved in WT pathogenesis include:

• WT1 gene: A tumor suppressor gene located on 11p13; required for normal kidney and gonadal development. Mutation of this gene is seen in WAGR syndrome, Denys-Drash syndrome, bilateral WT, and 10% of sporadic WT.
• WT2 gene: Located on 11p15; mutation in the form of deletion or overexpression is linked to familial WT and BWS.
• Additional WT loci include 16q, 1p, and p53 (located at 17p13). Mutations in these loci are associated with poor prognosis.

• The etiology is unknown.
• The pathophysiology is characterized by an abnormal proliferation of the metanephric blastema.
• Histology shows 3 components:
  • Primitive metanephric blastema
  • Dysplastic tubules
  • The mesenchyme
• The degree of differentiation of each component determines whether the tumour has favourable or unfavourable histology.

• WT can arise anywhere within the kidney.
• It distorts the renal architecture, unlike neuroblastoma which only displaces the kidneys downward without distorting its architecture.
• Spreads beyond a tumour capsule into the renal sinus, intra-renal lymphatics, and blood vessels → metastases (commonly to the lungs and liver).
• Vigorous abdominal palpation spills the cells into the abdominal cavity and encourages dissemination.

• MACROSCOPY: WT is sharply demarcated and variably encapsulated with haemorrhagic areas and cavitations. Location may be central or polar.
• MICROSCOPY: Three components seen in normal kidney differentiation—blastema, tubules, and stroma—are present. Based on microscopy, there are two broad variants:
  • Unfavorable histology: Presence of anaplasia—cells with nuclear enlargement, hyperchromatic nuclei, and abnormal mitotic figures. Anaplasia is the single most important indicator of poor prognosis.
  • Favorable histology: WT without anaplastic features.

The National Wilm’s Tumor Study Group (NWTSG) staging system is universally accepted
Stage	Description
Stage I	Tumor limited to kidney and completely resected
Stage II	Tumor extends beyond the kidney but is completely excised
Stage III	Residual non-haematogenous tumour confined to the abdomen
Stage IV	Haematogenous metastases
Stage V	Bilateral tumour

• Asymptomatic flank mass is the most common feature (Crosses the midline in 10% of cases).
• Abdominal pain in 30-40% of cases.
• Gross haematuria in 5-10% of cases.
• Constipation from pressure effect.
• Severe anaemia with fatigue (secondary to haematuria).
• Mild to moderate hypertension in 10% of cases.
• Fever from tumour necrosis.
• Cough.
• Dyspnea from pulmonary metastases.

• Ultrasound (abdomen) – Initial screening tool.
• Intravenous urogram – Shows distorted calyces or failure to excrete the dye (non-functional kidney).
• Computed tomography scan:
  • Differential diagnosis of a kidney tumour versus adrenal tumour (neuroblastoma).
  • Liver metastases.
• Chest x-ray – As a baseline for pulmonary metastases.
• Magnetic resonance imaging.
• Biopsy should be avoided to prevent spillage.

• It is a potentially curable tumour.
• Surgical therapy: The first step is surgical staging followed by radical nephrectomy, if possible.
• If the tumour is unresectable, biopsies are performed and the nephrectomy is deferred until after chemotherapy, which will shrink the tumour in most cases.
• Adjuvant chemotherapy has improved disease-free survival.
• The cytotoxic agents used are:
  • Vincristine
  • Actinomycin-D
  • Adriamycin
• Radiotherapy is only useful if there is residual bulk disease after surgery.

• Neuroblastoma
• Hepatoblastoma
• Rhabdomyosarcoma
• Benign cystic tumour of the kidney

• With the advent of multimodal therapy, the prognosis is good.
• The overall cure rate approaches 80-85%.
• Cases with diffuse anaplasia and stage III or IV that recur in spite of the complex therapy have a bad prognosis.