Nephroblastoma, also known as Wilms Tumour, is an embryonal malignancy that arises within the kidney.
Epidemiology
Nephroblastoma is rare (1/8000 children). It usually presents in the 2nd year of life and nearly all cases occur before the age of 10. It is more common in African-Americans and less common in Asian populations.
Aetiology
The aetiology of nephroblastoma is unknown. Some cases possess a deletion on chromosome 11 involving the WT1 (Wilms Tumour 1) gene. This is a zinc finger protein, functioning as a transcription factor and is important in the development of the urogenital system. Familial nephroblastoma is uncommon but many of these cases harbour a mutation in WT1.
Natural History
Nephroblastoma usually confined to the kidney. Metastases may occur but are restricted to the liver, lungs or regional lymph nodes.
There is no known pre-invasive lesion.
Clinical Presentation
Patients may present in varying ways:
- Most commonly, with an incidental abdominal mass noted by parents
- Symptoms relating to the enlarging mass (pain)
- Symptoms relating to involvement of the renal system (haematuria, hypertension)
- Rarely, anaemia or polycythaemia (secondary to production of erythropoeitin by the tumour)
On examination, the most common finding is an abdominal mass. Imaging usually demonstrates a heterogenous mass arising from the kidney, distorting the normal architecture. The mass is often very large.
Syndromes
10% of patients present with nephroblastoma together with other syndromic features. This includes:
- WAGR Syndrome: WAGR stands for Wilms tumour, aniridia, genitourinary malformation and mental Retardation. Patients with the other features of the syndrome have a 30% lifelong risk of nephroblastoma. This syndrome is due to a deletion of part of chromosome 11 that includes the WT1 gene.
- Denys-Drash Syndrome: Denys-Drash is another rare syndrome, comprising mesangial sclerosis and pseudohermaphroditism. This carries a 90% risk of nephroblastoma. This syndrome is due to a somatic mutation in the WT1 gene rather than a deletion.
- Beckwith-Weidemann Syndrome: This is a rare condition resulting from a deletion of another part of chromosome 11, from a genetic locus designated WT2 (Wilms Tumour 2); the exact gene has not been determined. The syndrome also consists of macrosomia, hemihypertrophy, macroglossia, omphalocele and visceral hypertrophy.
- Familial nephroblastoma can also occur, usually due to mutations of the WT1 gene.
Tumour/Normal Tissue Features
Macroscopically the tumour is a uniform grey to tan colour. It is usually separated from the kidney by a pseudo capsule. Cysts or calcium deposits may be present.
Microscopic appearance is complex:
- The tumour is characterised by a blastemal cell population as well as other cells that resemble differentiation into epitheliod or mesenchymal structures.
- The blastemal component is characterised by small round blue cells with scant cytoplasm.
- The architecture of the blastemal component may vary but usually forms serpentine or nodular structures.
- A less common form is diffuse, where there is less cellular cohesion and extensive invasion of neighbouring structures
- Epithiliod components usually resemble primitive forms of nephrogenesis
- Cells may form tubular structures or more complex papillary patterns
- Occasionally cells may differentiate into mucinous or squamous patterns.
- Mesenchymal or stromal differentiation is usually present as areas of smooth or striated muscle
- Occasionally the stromal component may be the only cell population present in the tumour
- Other stromal structures can be formed, including cartilage, bone or glial cells
An important variant is the presence of anaplasia. These tumours are associated with a worse prognosis and are diagnosed by the presence of multipolar mitoses and enlarged, hyperchromatic nuclei.
Immunohistochemistry is usually positive for vimentin, and the different cell populations may stain positively for desmin or cytokeratins.
Aside from the WT1 and WT2 gene abnormalities seen in several syndromes (see above), there are no other specific genetic abnormalities seen in nephroblastoma.
Staging / Classification
Nephroblastoma is staged using either the International Society of Paediatric Oncology (SIOP) or Children's Oncology Group (COG) system. In both systems the staging is surgical. The differences between the two systems are minor; they are highlighted in red
SIOP Staging
| Stage | Description |
|---|---|
| I | Completely resected; tumour is limited to the kidney; or if beyond the kidney the tumour is confined by the pseudocapsule |
| II | Completely resected; tumour directly invades adjacent structures such the IVC, adrenal glands or pancreas etc. |
| III | Incompletely excised tumour, due to * Involvement of surgical margins * Involvement of abdominal lymph nodes * Peritoneal contamination by tumour or intraoperatively * Residual abdominal tumour * Non-contigous resection / piecemeal resection * Biopsy of tumour prior to neoadjuvant chemotherapy * Presence of necrotic tumour or chemotherapy changes in margins or nodes |
| IV | Haematogenous or non-abdominal lymph node metastases |
| V | Bilateral tumours; each tumour should be sub-staged as above |
COG Staging
| Stage | Description |
|---|---|
| I | Completely resected; tumour is limited to the kidney and the renal capsule is intact |
| II | Completely resected; tumour directly invades adjacent structures such the IVC, adrenal glands or pancreas etc. |
| III | Incompletely excised tumour, due to * Involvement of surgical margins * Involvement of abdominal lymph nodes * Peritoneal contamination by tumour or intraoperatively * Residual abdominal tumour * Non-contigous resection / piecemeal resection |
| IV | Haematogenous or non-abdominal lymph node metastases |
| V | Bilateral tumours; each tumour should be sub-staged as above |
