Wilms' tumor

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Wilms' tumor
ICD-10 C64
ICD-9 189.0
ICD-O: M8960/3
OMIM 194070 607102
DiseasesDB 8896
eMedicine med/3093  ped/2440
MeSH D009396

Wilms' tumor is a neoplasm of the kidneys that typically occurs in children. It is eponymously named after Dr. Max Wilms, a German surgeon (1867-1918) who first identified this form of cancer. It is also known as a nephroblastoma.

Approximately 500 cases are diagnosed in the U.S. annually. The majority (75%) occur in otherwise normal children; a minority (25%) is associated with other developmental abnormalities. It is highly responsive to treatment, with about 90% of patients surviving at least five years.

Presentation

Wilms' tumor can affect any child regardless of race, sex, country of origin, or parental occupation. There is increased incidence among siblings and identical twins. The disease is mostly noticed around age three, but has been recorded in people at the age of 32. Most cases begin with experience of the following symptoms:

It can be associated with a WAGR complex. This complex includes Wilms' Tumor, aniridia, genitourinary malformation, and mental motor retardation. It can also be associated with Beckwith-Wiedemann syndrome (hemihypertrophy, macroglossia, omphalocele).

Pathology

Pathologically, a triphasic nephroblastoma comprises three elements:

Wilms' tumor is a malignant tumor containing metanephric blastema, stromal and epithelial derivatives. Characteristic is the presence of abortive tubules and glomeruli surrounded by a spindled cell stroma. The stroma may include striated muscle, cartilage, bone, fat tissue, fibrous tissue. The tumor is compressing the normal kidney parenchyma. Pathology images

The mesenchymal component may include cells showing rhabdomyoid differentiation. The rhabdomyoid component may itself show features of malignancy (rhabdomyosarcomatous Wilms).

Wilms tumor may be separated into 2 prognostic groups based on pathologic characteristics:

  • Favorable - Contains well developed components mentioned above
  • Anaplastic - Contains diffuse anaplasia (poorly developed cells)

Molecular biology

Mutations of the WT1 gene on chromosome 11 are observed in approximately 20% of Wilms' tumors.[2][3] At least half of the Wilms' tumors with mutations in WT1 also carry mutations in CTNNB1, the gene encoding the proto-oncogene beta-catenin.[4]

A gene on the X chromosome, WTX, is inactivated in up to 30% of Wilms' tumor cases, according to research published in 2007.[5]

Staging and treatment

Staging is determined by combination of imaging studies, and pathologic findings if the tumor is operable (adapted from www.cancer.gov). Treatment strategy is determined by the stage:

Stage I (43% of patients)

For stage I Wilms' tumor, 1 or more of the following criteria must be met:

  • Tumor is limited to the kidney and is completely excised.
  • The surface of the renal capsule is intact.
  • The tumor is not ruptured or biopsied (open or needle) prior to removal.
  • No involvement of renal sinus vessels.
  • No residual tumor apparent beyond the margins of excision.

Treatment: Nephrectomy + 18 weeks of chemotherapy

Outcome: 98% 4-year survival; 85% 4-year survival if anaplastic

Stage II (23% of patients)

For Stage II Wilms' tumor, 1 or more of the following criteria must be met:

  • Tumor extends beyond the kidney but is completely excised.
  • No residual tumor apparent at or beyond the margins of excision.
  • Any of the following conditions may also exist:
    • Tumor involvement of the blood vessels of the renal sinus and/or outside the renal parenchyma.
    • The tumor has been biopsied prior to removal or there is local spillage of tumor during surgery, confined to the flank.

Treatment: Nephrectomy + abdominal radiation + 24 weeks of chemotherapy

Outcome: 96% 4-year survival; 70% 4-year survival if anaplastic

Stage III (23% of patients)

For Stage III Wilms' tumor, 1 or more of the following criteria must be met:

  • Unresectable primary tumor.
  • Lymph node metastasis.
  • Positive surgical margins.
  • Tumor spillage involving peritoneal surfaces either before or during surgery, or transected tumor thrombus.

Treatment: Abdominal radiation + 24 weeks of chemotherapy + nephrectomy after tumor shrinkage

Outcome: 95% 4-year survival; 56% 4-year survival if anaplastic

Stage IV (10% of patients)

Stage IV Wilms' tumor is defined as the presence of hematogenous metastases (lung, liver, bone, or brain), or lymph node metastases outside the abdomenopelvic region.

Treatment: Nephrectomy + abdominal radiation + 24 weeks of chemotherapy + radiation of metastatic site as appropriate

Outcome: 90% 4-year survival; 17% 4-year survival if anaplastic

Stage V (5% of patients)

Stage V Wilms’ tumor is defined as bilateral renal involvement at the time of initial diagnosis. Note: For patients with bilateral involvement, an attempt should be made to stage each side according to the above criteria (stage I to III) on the basis of extent of disease prior to biopsy. The 4-year survival was 94% for those patients whose most advanced lesion was stage I or stage II; 76% for those whose most advanced lesion was stage III.

Treatment: Individualized thereapy based on tumor burden

Stage I-IV Anaplasia

Children with stage I anaplastic tumors have an excellent prognosis (80-90% five-year survival). They can be managed with the same regimen given to stage I favorable histology patients.

Children with stage II through stage IV diffuse anaplasia, however, represent a higher-risk group. These tumors are more resistant to the chemotherapy traditionally used in children with Wilms’ tumor (favorable histology), and require more aggressive regimens.

See also

External links

International WAGR Syndrome Association http://www.wagr.org

References

  1. "MedlinePlus Medical Encyclopedia: Wilms tumor". Retrieved 2007-07-11.
  2. Call K, Glaser T, Ito C, Buckler A, Pelletier J, Haber D, Rose E, Kral A, Yeger H, Lewis W (1990). "Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus". Cell. 60 (3): 509–20. PMID 2154335.
  3. Huff V (1998). "Wilms tumor genetics". Am J Med Genet. 79 (4): 260–7. PMID 9781905.
  4. Maiti S, Alam R, Amos CI, Huff V (2000). "Frequent association of beta-catenin and WT1 mutations in Wilms tumors". Cancer Res. 60 (22): 6288–92. PMID 11103785.
  5. Rivera M, Kim W, Wells J, Driscoll D, Brannigan B, Han M, Kim J, Feinberg A, Gerald W, Vargas S, Chin L, Iafrate A, Bell D, Haber D (2007). "An X chromosome gene, WTX, is commonly inactivated in Wilms tumor". Science. 315 (5812): 642–5. PMID 17204608.

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