Wilms’ tumour, the most common primary renal tumour in children, classically presents as an asymptomatic abdominal mass characterised by a triphasic histological pattern with blastemal, epithelial, and stromal components, with a large, encapsulated renal mass often crossing the midline.
Description
Wilms tumour, also known as nephroblastoma, is a type of paediatric malignancy that originates in the kidneys. It’s the most common primary renal tumour in children and accounts for approximately 90% of all childhood renal malignancies.
Pathogenesis
The pathogenesis of Wilms tumour is related to the abnormal proliferation of metanephric blastemal cells, which are embryonic precursors to renal cells. Certain genetic mutations have been implicated in the development of Wilms tumour, including changes in the WT1 (most common) and WT2 genes on chromosome 11.
In addition to these genetic mutations, nephrogenic rests, which are abnormally persistent clusters of embryonic renal cells, are frequently associated with Wilms tumour. Nephrogenic rests can be considered precursor lesions and are found in the kidneys of approximately 40% of patients with Wilms tumour. These rests are thought to arise due to a failure in the normal differentiation and maturation of metanephric blastemal cells during kidney development, providing a substrate for subsequent malignant transformation.
Wilms tumours are composed of a triphasic mixture of blastemal, stromal, and epithelial cell types, which reflects its origin from multipotent embryonic renal cells.
Epidemiology, Risk Factors and Associations
- Wilms tumour primarily affects children aged 2 – 5 years old, with a peak at 3 years old.
- There are slightly more cases in females than males.
- The most significant association with Wilms tumour is genetic predisposition:
- Around 10-15% of children with Wilms tumour have an underlying genetic condition, most commonly a mutation in the WT1 gene or WT2 (less common) on chromosome 11.
- WAGR syndrome (Wilms tumour, Aniridia, Genitourinary abnormalities, and mental Retardation)
- Denys-Drash syndrome (male pseudohermaphroditism with gonadal dysgenesis and nephropathy).
- Overgrowth syndromes:
- Beckwith-Wiedemann syndrome: Characterised by overgrowth/organomegaly, abdominal wall defects, increased risk of embyronal tumour (5-10% of cases).
- Sotos syndrome and Perlman syndrome
- Undescended testicles (cryptorchidism) in males have been linked to an increased risk of Wilms tumour in 1 – 2% of cases.
- Nephrogenic rests (NR): Metanephric blastema that persists after 36-weeks gestation; precursor to Wilms tumour
- Nephroblastomatosis refers to the presence of multiple or diffuse NR. Seen in 99% of cases of bilateral Wilms tumour.
Clinical Features
- The most common clinical feature is an asymptomatic abdominal mass.
- Other symptoms may include abdominal pain, haematuria, hypertension, and fever.
- Occasionally, the disease may be discovered due to complications such as haemorrhage or bowel obstruction.
Complications
- Intra-abdominal spread secondary to tumour rupture, spreading malignant cells within the abdomen which can then implant on peritoneal surfaces leading to local recurrence or metastases.
- Obstruction of the urinary tract, leading to hydronephrosis or hydroureter. Similarly, bowel obstruction can occur.
- Vascular invasion, specifically the renal vein or inferior vena cava, potentially leading to Budd-Chiari syndrome.
- Hypertension occurs due to increased renin production from the renal tumour cells.
- Metastasis most commonly to the lungs, but can also spread to the liver, bone or regional lymph nodes.
- Treatment-related complications
- Chemotherapy: Myelosuppression, hair loss, nausea, vomiting, mucositis, hearing loss (cisplatin), kidney damage (ifosfamide).
- Radiation Therapy: Potential for growth disturbance in children, damage to nearby organs, secondary malignancies.
- Surgery: Postoperative complications include pain, bleeding, infection, and damage to surrounding organs.
- Long-term complications include late effects related to treatment, including renal failure (especially in bilateral disease), cardiac disease (related to doxorubicin), infertility, and risk of secondary cancers.
Pathological Features
Histopathology
Classic Wilms tumours show a triphasic pattern with blastemal, epithelial, and stromal components. However, some tumours may predominantly show one component.
- Blastemal Component: This is composed of small, blue cells that are poorly differentiated. They often form clusters or sheets. The blastemal component is typically the most aggressive, and a predominance of this type within the tumour is associated with a poorer prognosis.
- Epithelial Component: This component is composed of tubules or glomerulus-like structures, indicative of a more differentiated state. The tubules resemble those seen in normal kidney development, reflecting the tumour’s origin in nephrogenic rests.
- Stromal Component: The stromal component can vary widely in appearance, ranging from fibrous tissue to muscle or even cartilage. It tends to resemble the supportive tissues found throughout the body, and it’s generally the least aggressive of the three components.
Nephrogenic rests are focal lesions of persistent embryonic renal precursors, seen in the renal parenchyma adjacent to 40% of unilateral tumours and almost 100% of bilateral tumours.
Biochemistry
There are no specific biochemical markers for Wilms tumours, but some patients may have elevated levels of certain substances in the blood or urine, such as lactate dehydrogenase (LDH), which can indicate the presence of a tumour.
Radiological Features
General Features
- Ultrasound useful for confirmation of renal mass. Contrast-enhanced CT/MR to characterise tumour. Chest CT for staging.
- Most commonly metastasises to the lungs, but can also spread to the liver, bone or regional lymph nodes.
- Typically unilateral (90%), large (5 – 10 cm), rounded/lobulated with a smooth contour
XR
- Mass displacing adjacent bowel
US
- Large, well-circumscribed, heterogeneous masses that can cause distortion of the renal outline.
- Claw sign – splayed renal tissue surrounding tumour margin.
- Colour doppler can assess for renal vein/IVC tumour thrombus.
CT
- Appear as large, intrarenal masses that can cause distortion of the kidney.
- Claw sign
- Heterogeneous due to areas of haemorrhage, necrosis, or cystic change.
- Calcifications are less common than in neuroblastoma, seen in about 15% of cases and tend to be fine or punctate.
- Chest: 20% have lung metastases (well-defined solid nodules) at time of diagnosis.
MRI
- T1: Typically heterogenous with isointense to slightly hypointense compared to normal renal parenchyma. Foci of high signal may indicate haemorrhage.
- T2: Heterogeneous high signal intensity due to a combination of cellular tumour, necrosis, cysts, and haemorrhage.
- T1 Gd+:Typically demonstrates heterogenous enhancement.
- DWI: Solid components typically show restricted diffusion due to their high cellularity.
Multiphase post-contrast imaging: Helpful in identifying tumour extension into the renal vein and inferior vena cava, a characteristic more typical of Wilms tumour. This appears as an intermediate signal intensity filling defect within the vessels on all sequences.
PET
- Typically FDG-avid
Staging
The staging system for Wilms’ tumour, as defined by the National Wilms Tumour Study Group (NWTSG) and the International Society of Paediatric Oncology (SIOP), is as follows:
Stage I
- The tumour is limited to the kidney and is completely excised.
- The renal capsule is intact.
- The tumour is not ruptured or biopsied (open or needle) prior to removal.
- No residual tumour is apparent beyond the margins of excision.
Stage II
- The tumour extends beyond the kidney but is completely excised.
- This includes cases with local spillage confined to the flank, or tumour in the vessels outside the renal parenchyma but still within the confines of the completely resected area.
Stage III
- Residual non-haematogenous tumour is confined to the abdomen.
- This can include one or more of the following: lymph node metastasis, penetration of the peritoneal surface, spillage of tumour cells either before or during surgery, or tumour left behind after surgery that is not removable.
Stage IV
- Haematogenous metastases (lung, liver, bone, brain), or lymph node metastases outside the abdominal cavity.
Stage V
- Bilateral renal involvement at the time of initial diagnosis.
- For patients with bilateral Wilms tumours, an attempt should be made to stage each side according to the above criteria (i.e., Stage V-I, Stage V-II, Stage V-III).
Diagnosis
- Wilms tumours typically are not biopsied preoperatively to avoid tumour seeding and because imaging provides sufficient diagnostic certainty.1
Prognosis
- Overall survival rate for Wilms tumour is high, with approximately 90% of children being cured.
- Younger age at diagnosis and localised disease (stage I or II) are associated with a more favourable prognosis.
- Favourable histology characterised by triphasic pattern and absence of significant anaplasia.
Differential Diagnosis
- Neuroblastoma, especially when it presents as a large abdominal mass.
- Seen in young children (2 years), vs. 3-4 years in Wilms tumour
- Usually arises from the adrenal gland or paraspinal ganglia. A neuroblastoma arising from the adrenal gland will displace the kidney downwards and laterally, while a Wilms tumour usually displaces the kidney anteriorly and contralaterally. Neuroblastoma also readily crosses the midline, whereas Wilms tumours rarely cross.
- Calcification is more common in neuroblastoma (90%) and often coarse or ‘clumped’. If present in Wilm’s tumour (10%), tends to be fine and punctate
- Intratumoural haemorrhage or necrosis is more common in neuroblastoma, leading to a heterogenous appearance.
- Wilm’s tumour can grow into the renal vein and IVC, more so than neuroblastoma, which encases vessels
- Lung metastases are rarer in neuroblastoma (10% of cases) whereas they are seen in 85% of metastatic Wilms tumours.
- Nephroblastomatosis: Persistent of nephrogenic rests. Can progress to Wilms tumour. Small nodules or masses within the kidney.
- Mesoblastic nephroma: Most common neonatal/infant renal tumour. Benign. Diagnosed on prenatal ultrasound. Excellent prognosis with surgical resection.
- Multicystic nephroma: Large renal cysts which do not communicate. Septal enhancement. Bimodal occurence: males (around 4 years of age) and middle age women (around 40 years).
- Other renal tumours such as clear cell sarcoma of the kidney or rhabdoid tumour of the kidney.
- Renal cysts or other benign kidney conditions.
Management
- Treatment for Wilms tumour typically includes a combination of surgery, chemotherapy, and sometimes radiotherapy.
- Preoperative chemotherapy is often used to shrink the tumour and make it easier to remove surgically.
References