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Wilms Tumor Fiji National University

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					                                       Wilms Tumor
Wilms Tumor is the most common renal malignancy in children and the 4th most common cause of
childhood cancer.

Epidemiology:
     The annual incidence of Wilms tumor is about 8 cases per million children under the age of
       15.
     Wilms tumor accounts for 6.6 percent of childhood malignancies with 500 new cases
       presenting each year.
     In the US, two-thirds are diagnosed before 5 years of age, and 95% before 10 years of age.
     There can be unilateral or bilateral involvement
     The incidence is slightly higher in girls than in boys
     The Wilms tumor is greater in African-American children than in non-Hispanic white children;
       lower in Asians compared to Caucasian children.

Associated congenital syndromes: In some children, Wilms tumor occurs as a part of a multiple
malformation syndrome. These syndromes include WADR, Denys-Drash, and Beckwith-Wiedemann
syndromes.

Syndrome                            Clinical Characteristics               Chromosomes or other
                                                                           abnormalities
WAGR                                Aniridia, genitourinary                Del 11p13 (WTI & PAX6 loci)
                                    abnormalities, mental retardation

Denys-Drash                         Early onset renal failure with renal   WT1 mutations
                                    mesangial sclerosis, male
                                    pseudohemaphroditism, increase
                                    risk of Wilms Tumor (60%)
Beckwith-Wiedemann                  Organomegaly (liver, kidney,           Duplication 11p15.5, loss of
                                    adrenal, pancreas), macroglossia,      imprinting, mutation of p57KIP57
                                    omphalocele, hemihypertrophy           and Del 11p15.5. Uniparental
                                                                           paternal disomy.

Pathogenesis:




      Wilms tumor is appears to be caused by abnormal renal development, resulting in
       proliferation of the metanephric blastema without normal tubular and glomerular
       differentiation.

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      Wilms tumor is thought to arise from foci of persistent metanephric cells referred to as
       nephrogenic rests or nephroblastomatosis.
      Nephrogenic rests normally occur in 1% of newborn kidneys and regress early in childhood.
       In contrast, they are present in 35% of kidneys with unilateral Wilms tumor and almost 100%
       of kidneys with bilateral disease.

   Genetics:
       Wilms tumor has been associated with loss of function mutations of a number of tumor
          suppressor genes. These include mutations of the WT1, p53, FWT1 & FWT2 genes and
          at the 11p15.5 locus. The role of these gene mutations in the pathogenesis of Wilms
          tumor remains unknown.




       Pathology:
           Grossly, Wilms tumor tends to present as a large, solitary, well-circumscribed mass
              with a pseudocapsule.
           7% of patients have bilateral renal involvement and 12% have multifocal loci within
              a single kidney.
           On cut section, the tumor is soft, typically gray or tan, there may be cysts,
              hemorrhage, or necrosis present.
           Histologically, the classic tumor is comprised of 3 cell types:
               a) Blastemal cells – undifferentiated cells
              b) Stromal cells- immature spindle cells and heterologous skeletal muscle, cartilage,
              osteoid, or fat
              c) Epithelial cells- Glomeruli and tubules
           It metastasizes most frequently to the lungs (80% of cases). Regional extension may
              occur as it breaks through the renal capsule or involves the regional lymph nodes.

Clinical manifestations:
          Abdominal mass- most common clinical presentation. Physical examination reveals a
            firm, non tender, smooth mass that rarely crosses the midline and generally does not
            move with respiration. This differentiates it from neuroblastoma and splenomegaly
            which often extend across the midline and move with respiration.
          abdominal pain (30% of patients)


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               hematuria (12-25% of patients)
               hypertension (25% of patients, this is due to ↑renin due to renal ischaemia usually from
                pressure by the tumor on the renal artery)

Patients with subcapsular hemorrhage can present with:
                 Rapid abdominal enlargement
                 Anaemia
                 Hypertension
                 Occasionally fever

Diagnosis:
     The definitive diagnosis of Wilms tumor is made by histologic confirmation at the time of
       either surgical excision or biopsy.
     Imaging maybe used to differentiate Wilms tumor from other causes of abdominal masses
       such as abdominal ultrasound, Doppler ultrasonography, CT scan.
     CXR – to determine lung metastasis.
     Laboratory studies: Urinalysis, liver function, FBC, UECrCl, Serum calcium.

Staging:
     Two major systems are in use:
        1) National Wilms Tumor Study (NWTS) - This is based upon surgical evaluation prior to the
           administration of chemotherapy. Used in the US and Canada.
        2) International Society of Padiatric Oncology (SIOP) – This system is based upon post-
           chemotherapy surgical evaluation. Used in Europe.

           Staging system developed by the TNWT study group. First 4 stages are confined to unilateral
            involvement.

Stage I                                                Tumor is limited to the kidney. The tumor is
                                                       completely resected with an intact capsule.
Stage II                                               Tumor extends beyond the kidney but is
                                                       completely resected without evidence of tumor
                                                       at or beyond the margins of resection.
Stage III                                              After surgery, residual tumor remains but is
                                                       confined to the abdomen.
Stage IV                                               Hematogenous metastasis (eg, lung, liver, bone,
                                                       brain) or lymph node involvement beyond the
                                                       abdominopelvic region
Stage V                                                Bilateral renal involvement is present at the time
                                                       of diagnosis

Treatment:
Depends on the staging and histology and requires multimodal therapy:
     Stage I and II- primay surgical resection + 18 weeks of vincristine and dactinomycin.
     Stage III- Primary Surgical resection is + 24 weeks of triple drug chemotherapy of vincristine,
       dactinomycin and doxorubicin + radiation therapy at affected flank.
     Stage IV- primary surgical resection + 24 weeks triple drug chemotherapy + radiation therapy
       only if the lung metastasis do not completely respond to 6 weeks of chemotherapy.
     Stage V- main therapeutic goal is to adequately treat the bilateral tumor loci while trying to
       preserve renal function. Possibly a partial nephrectomy of the more involved site.


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Prognosis:
    Major prognostic factors are tumor size, stage, and histology. The prognosis is worse in
       patients with a larger tumor (>500  g), advanced stage (III and IV), and unfavorable
       histologic subtype. Nonetheless, Wilms tumor constitutes a paradigm of successful
       multidisciplinary treatment; more than 60% of patients with all stages generally survive.
       Stages I through III have a cure rate varying from 88–98%.

References:
    Nelsons Textbook of Pediatrics, 15th Edition, Behrman, Kliegman, Arvin
    www.uptodate.com
    Pathologic Basis of Disease, 7th Edition, Kumar, Abbas, Fausto.



Kula Baravi
MBBS 4 2009




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posted:3/11/2011
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