Wilms' tumor

Wilms' tumor or nephroblastoma is a tumor of the kidneys that typically occurs in children, rarely in adults. Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon (1867-1918) who first described this kind of tumor.^[1]

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.

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Pathology

Pathologically, a triphasic nephroblastoma comprises three elements:

• blastema
• mesenchyme
• epithelium

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.

Treatment

Once a kidney tumor is found, surgery can find out whether or not the tumor is cancer. A sample of tissue from the tumor is sent to a pathologist, who looks at it under a microscope to check for signs of cancer. If the tumor is only in the kidney, it can be removed along with the whole kidney (a process called nephrectomy). If there are tumors in both kidneys or if the tumor has spread outside the kidney, a piece of the tumor will be removed.

See also

• National Wilms Tumor Study Group (NWTS)

References

1. ^ WhoNamedIt.com: Max Wilms
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.