Nephroblastoma |Wilm’s Tumour

 Introduction and Epidemiology

The commonest solid tissue tumours in childhood include nephroblastoma, retinoblastoma, rhabdomyosarcoma and neuroblastoma.

Of these, nephroblastoma is the commonest.

It arises from poorly differentiated cells in the kidneys. It is the most common renal tumour in children comprising 90% of all kidney cancers. 

Epidemiology.

Globally, the incidence is estimated to be between 5 -10 per million with peak before the age of 5 years.

According to the Eldoret (AMPATH) cancer registry, Wilms tumour constitutes 17.4% of childhood cancers.

Retinoblastoma and nephroblastoma have strong familial tendencies; especially variaties that present within the first year year of Life.

Majority of nephroblastoma present without associated physical findings (sporadic). A smaller number (familial) occur in association with congenital anomalies such as aniridia, hemihypertrophy and genitourinary anomalies. 

These findings in an infant with a positive family history should increase index of suspicion for kidney tumour. 

 Diagnosis

The commonest solid tissue tumours in childhood include nephroblastoma, retinoblastoma, rhabdomyosarcoma and neuroblastoma.

Of these, nephroblastoma is the commonest. It arises from poorly differentiated cells in the kidneys.

It is the most common renal tumour in children comprising 90% of all kidney cancers. 

presentation

Nephroblastoma most commonly presents as painless abdominal swelling though gross or microscopic haematuria and hypertension occur less often.

This emphasizes the importance of full physical examination for children even when they present with unrelated clinical problems as most cases are detected by chance.

Nephroblastomatosis, mesoblastic nephroma, bilateral nodular renal blastema and nonmalignant conditions like hydronephrosis should be excluded in those less than 2 years with bilateral renal involvement.

Very similar presentation to that of neuroblastoma making it difficult to diffrentiate those with early disease without imaging or laboratory support.

A chest radiograph is a valuable diagnostic tool in looking for metastasis in these conditions.

Nephroblastoma metastases occur in lung parenchyma, as opposed to those from neuroblastoma that tend to deposit in the posterior mediastinum.

Renal sonography is the preferable imaging study in diffrentiating the two as it provides better tissue cleavage without ionizing radiation though some may require optimized IVU studies.

CT scan of chest at diagnosis is useful.

Defiitive diagnosis of nephroblastoma is made histologically on tissue biopsy which also has prognostic implications and classifid into classical and atypical.

Classical histology is graded as “favourable” or “unfavourable”.

Most tumours exhibit triphasic appearance comprising of blastemal, stromal and epithelial cell types though some may exhibit only two or one.

Line of diffrentiation determines the designated tumour histiotype.

Malignant rhabdoid tumour (MRTK) and clear cell sarcoma are considered diffrent entities from typical nephroblastoma.

Predominantly blastemal histology is associated with more  aggressive disease while stromal, especially with tendency to differentiation into skeletal  muscle, demonstrate good response to treatment.

Staging and risk management

National Wilms Tumor Study (NWTS):

(Clinical pathologic staging considers tumour dynamics and resectability and is the most preferred)

Stage I: Tumour limited to the kidney and completely excised
Stage II:  Tumour extends beyond the kidney but completely excised. Invasion of 
 renal sinus and/or extra renal vessels and/or peri-renal fat
Stage III:  Invasion beyond capsule, any abdominal lymphnodes, tumour rupture, 
 peritoneal tumour implants or incomplete excision
Stage IV:  Haematogenous metastasis (lung, liver, bone, brain and lymphnodes) 
 outside abdominal pelvic region
Stage V:  Bilateral renal tumours at diagnosis

 

Management

 Supportive Management.

 See general guidelines. Majority of children present in fairly good condition though those  with stage IV and V may be wasted and septic. 

Specific Management.

National Wilms Tumour Study (NWTS) and Internal Society of Paediatric Oncology (SIOP) guidelines are the most widely used. 

Management of Nephroblastoma

Stage I  adjuvant Vincristine and actinomycin D without radiotherapy except 
 for patients with unfavourable histology. No need for maintenance and  radiotherapy.
Stage II  adjuvant vincristine and actinomycin D without radiotherapy except for 
 those with unfavourable histology. No need for maintenance and 
 radiotherapy
Stage III and 
earlier stage 
disease with 
unfavourable 
histology –
Three drug adjuvant treatment with vincristine, actinomycin D and 
Adriamycin for a longer duration. Radiotherapy of renal bed and whole 
abdomen for those with positive nodes and tumour spillage. Radiotherapy 
should be avoided in children under the age of 2 years.
Stage IV –  Three drug adjuvant treatment with vincristine, actinomycin D and 
 Adriamycin as in stage III. Radiotherapy is limited to residue 
 metastatic lesions, especially in the lungs. Surgical excision should be 
 considered prior to radiotherapy whenever feasible

Note: Stage II-IV with diffuse anaplastic tumours should have radiotherapy of the tumour bed.

 Response Evaluation.

•     Imaging studies should be advised by disease stage and sites involved.

Abdominal  ultrasound should be performed after induction and end of maintenance treatment. 

•  Chest radiograph is preferred for evaluation of those with lung metastasis.

•     Long term disease free survival for nephroblastoma in industrialized countries is  in excess of 90% as virtually all patients present with early stage disease.

Locally,  survival is estimated at about 50%. 

Follow-up.

•     Clinical assessments every 2 months in the first year then 6 monthly in the secondand third year; including monitoring of blood pressure.

Recurrences are uncommon after 3 years hence follow up annually.

•     Renal function tests including serum creatinine and protein-creatinine ratio three monthly in the first year then annually for 3 years then every 5 years as risk for  renal impairment is lifelong.

 Pharmacological management

Ifosfamide, etoposide, carboplatin, vincristine, actinomycin-D, anthracyclines.

In resource limited settings, Vincristine, actinimycin-D, doxorubicin is the first line  treatment.

This also applies where resources are available. 

Prognosis

These are curable in a majority of cases if diagnosed early. 

 References

  1.  Voute PA et al. Cancer in Children, 5th edition, oxford University Press, 2005.
     
  2. Clericuzio CL. (1993). Clinical phenotypes and Wilms tumor. Med Pediatr Oncol. 21:182-7.
     
  3.  Beckwith JB et al. (1996). Histological analysis of aggressiveness and responsiveness in Wilms’ tumor.     Med Pediatr Oncol 27:422-8.
     
  4.   Tournade MF et al. (1993). Results of sixth SIOP Wilms’ tumour study. J Clin Oncol 11:1014-23
     

Related posts:

Dr Mathu

Leave a Reply

Your email address will not be published. Required fields are marked *