WILMS' TUMOR
DEFINITION:
An embryonal renal neoplasm characterized usually by an abdominal
mass.
EPIDEMIOLOGY:
- incidence: 7/million
- prevalence: 1/12,000 live births
- 2nd most common extracranial solid tumor in children
- makes up 7% of all childhood cancers
- peak age of onset:
- 6 months - 10 years (greatest in first 5 years)
- risk factors:
- familial - autosomal dominant (in some families)
- chrom.#: 11p13
- gene: see below
- M = F
- most common renal cancer in children
PATHOGENESIS:
- tumor origin - kidney (bilateral in only 5%)
- Wilms' tumor is a nephroblastoma which can arise by a
variety of pathogenic pathways from primitive metanephric
blastema
- the gene for Wilms' tumor (WT2-1) is located at 11p13 and
encodes a DNA-binding protein that is expressed primarily in the
fetal kidney and in tissue that gives rise to the genitourinary
system
- inactivation of this gene may be responsible for the
occurrence of a Wilms' tumor (Pritchard-Jones et al., 1990)
- the candidate Wilms' tumor gene is predicted to encode a
Kruppel-like zinc-finger protein that is probably a
transcriptional factor
2. Constitutional Chromosome Abnormalities(4)
- Wilms' tumor
- Aniridia
- lack or defect of the iris
- Genitourinary Anomalies
- gonadal dysgenesis, hypospadias, cryptorchidism,
duplication of collecting system
- mental Retardation
- deletion of chromosome 11p13
- tumor develops at a younger age
- increased incidence of bilateral tumor
2. Beckwith-Wiedemann Syndrome
- rearrangement of chromosome 11p15
- hemihypertrophy
- see file in database
3. Drash Syndrome
- Wilm's Tumor
- Nephropathy - hypertension, proteinuria, renal failure
- Genitourinary Anomalies - ambiguous genitalia
4. Perlman Malformation Syndrome
CLINICAL FEATURES:
- abdominal mass
- abdominal pain
- hematuria - gross or microscopic, painless, in up to 25%
- hypertension - in 25% (due to renin-secreting tumor or
renovascular hypertension)
- others - fever, malaise, anemia, weight loss, left
varicocele
- syndromes - aniridia, hemihypertrophy, etc.
2. Metastases
- lung (10% have mets at time of diagnosis, isolated or
multiple)
- lymph nodes
- liver
- brain
- rare - bone, skin, pleura, heart, epidural space
INVESTIGATIONS:
- Abdominal X-Ray (rim-ring calcification), skeletal survey
- Abdominal Ultrasound (intra- or extrarenal, uni- or
bilateral, uni- or multi-focal, solid or cystic)
- Abdominal CT
- IVP - internal compression of calyceal system
2. For Metastases
2. Pathology
- usually confined to the kidney
- most of affected kidney usually replaced
- may be cystic
2. Histologic Types
- classic histology is triphasic: blastemal, epithelial,
and/or stromal elements
- constitute 90% of tumors: favourable prognosis
2. Anaplastic
- constitute 10% of tumors: unfavourable prognosis
STAGING:
- National Wilms' Tumor Society (NWTS)
- Stages I -> V
- staging system has prognostic significance
PROGNOSTIC INDICATORS:
2. Histology
- favourable or unfavourable
3. Basic Fibroblast Growth Factor (bFGF)
- a heparin-bound blood vessel-generating peptide associated
with the growth and spread of bladder, prostate, and kidney
cancer
- measured as pg/g creatinine in the urine
- for those with Stage III or IV, preoperative bFGF levels are
25x higher than in those with Stage I or II
- for those with persistent or recurrent Wilms' tumor,
post-operative bFGF levels are 100x higher than in those who
remain disease-free
- there is a 1.6x greater chance of tumor recurrence in those
with elevated postoperative bFGF levels
MANAGEMENT:
- primary and second-look operations
- removal of involved kidney with evaluation and biospy of the
opposite kidney
- explore for extension, lymph node involvement, liver
metastases
2. Chemotherapy
- actinomycin-D (1954) and vincristine (1963) +/- doxorubicin
3. Prognosis
- greater than 85% cure rare with current therapy
- Stage - Cure Rate
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