Wilms' tumor

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Wilms' tumor
Classification and external resources
Wilms tumor.jpg
Cut section showing two halves of a nephroblastoma specimen. Note the prominent septa subdividing the sectioned surface and the protrusion of tumor into the renal pelvis, resembling botryoid rhabdomyosarcoma.
ICD-10 C64
ICD-9 189.0
ICD-O: M8960/3
OMIM 194070 607102
DiseasesDB 8896
MedlinePlus 001575
eMedicine med/3093 ped/2440
MeSH D009396
CT Scan of 11 cm Wilms' tumor of right kidney in 13-month-old patient.

Wilms' (/vɪlmz/) tumor, Wilms tumor, or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults.[1] It is named after Dr Max Wilms, the German surgeon (1867–1918) who first described it.[2]

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

Pathology[edit]

Micrograph showing the characteristic triphasic pattern consisting of tubules, solid sheets of small round cells, and stroma. H&E stain.
High magnification micrograph showing the epithelial component (tubules). H&E stain.

Most nephroblastomas are unilateral, being bilateral in less than 5% of cases, although patients with Denys-Drash syndrome mostly have bilateral or multiple tumors.[3] They tend to be encapsulated and vascularized tumors that do not cross the midline of the abdomen. In cases of metastasis it is usually to the lung. A rupture of Wilms' tumor puts the patient at risk of hemorrhage and peritoneal dissemination of the tumor. In such cases, surgical intervention by a surgeon who is experienced in the removal of such a fragile tumor is imperative.

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.

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

Wilms' tumors 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)

Symptoms[edit]

Typical symptoms are:

  • an abnormally large abdomen
  • abdominal pain
  • fever
  • nausea and vomiting
  • blood in the urine (in about 20% of cases)
  • high blood pressure in some cases (especially if synchronous or metachronous bilateral renal involvement)

Diagnosis[edit]

The first sign is normally a painless abdominal tumor that can be easily felt by the doctor. An ultrasound scan, computed tomography scan, or MRI scan is done first. A tumor biopsy is not typically performed due to the risk of creating fragments of cancer tissue and seeding the abdomen with malignant cells.

Prognosis[edit]

The overall 5-year survival is estimated to be approximately 90%,[4] but for individuals the prognosis is highly dependent on individual staging and treatment. Early removal tends to promote positive outcomes.

Tumor-specific loss-of-heterozygosity (LOH) for chromosomes 1p and 16q identifies a subset of Wilms' tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.[5][6] Genome-wide copy number and LOH status can be assessed with virtual karyotyping of tumor cells (fresh or paraffin-embedded).

Molecular biology[edit]

Mutations of the WT1 gene on chromosome 11p13 are observed in approximately 20% of Wilms' tumors.[7][8] At least half of the Wilms' tumors with mutations in WT1 also carry mutations in CTNNB1, the gene encoding the proto-oncogene beta-catenin.[9]

A gene on the X chromosome, WTX, is inactivated in up to 30% of Wilms' tumor cases, according to research published in 2007.[10]

Most cases do not have mutations in any of these genes.[11]

Staging[edit]

Staging is determined by combination of imaging studies and pathology findings if the tumor is operable. Treatment strategy is determined by the stage:

Definitions of stages[edit]

Stage I (43% of patients)[edit]

For stage I Wilms' tumor, all 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 extrarenal or renal sinus lymph-vascular spaces
  • No residual tumor apparent beyond the margins of excision.
  • Metastasis of tumor to lymph nodes not identified.

Stage II (23% of patients)[edit]

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.
    • Extensive tumor involvement of renal sinus soft tissue.

Stage III (23% of patients)[edit]

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

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

Stage IV (10% of patients)[edit]

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.

Stage V (5% of patients)[edit]

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.

Prognosis and treatment[edit]

Statistics may sometimes show more favorable outcomes for more aggressive stages than for less aggressive stages, which may be caused by more aggressive treatment and/or random variability in the study groups. Also, a stage V tumor is not necessarily worse than a stage IV tumor.

Stage[12] Histopathology[12] 4 Year relapse-free survival (RFS) or event-free survival (EFS)[12] 4 Year overall survival (OS)[12] Treatment[12]
Stage I [12] Favorable histology in children younger than 24 months or tumor weight less than 550g 85% 98% Surgery only (should be done only within the context of a clinical trial)
Favorable histology in children older than 24 months or tumor weight more than 550g 94% RFS 98% Nephrectomy + lymph node sampling followed by regimen EE-4A
Diffuse anaplastic 68% EFS 80% Nephrectomy + lymph node sampling followed by regimen EE-4A and radiotherapy
Stage II[12] Favorable histology 86% RFS 98% Nephrectomy + lymph node sampling followed by regimen EE-4A
Focal anaplastic 80% EFS 80% Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen DD-4A
Diffuse anaplastic 83% EFS 82% Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen I
Stage III[12] Favorable histology 87% RFS 94% Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen DD-4A
Focal anaplastic 88% RFS 100% (8 people in study) Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen DD-4A
Focal anaplastic (preoperative treatment) 71% RFS 71% Preoperative treatment with regimen DD-4A followed by nephrectomy + lymph node sampling and abdominal radiotherapy
Diffuse anaplastic 46% EFS 53% Preoperative treatment with regimen I followed by nephrectomy + lymph node sampling and abdominal radiotherapy
Diffuse anaplastic 65% EFS 67% Immediate nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen I
Stage IV[12] Favorable histology 76% RFS 86% Nephrectomy + lymph node sampling, followed by abdominal radiotherapy, bilateral pulmonary radiotherapy, and regimen DD-4A
Focal anaplastic 61% EFS 72% Nephrectomy + lymph node sampling, followed by abdominal radiotherapy, bilateral pulmonary radiotherapy, and regimen DD-4A
Diffuse anaplastic 33% EFS 33% Immediate nephrectomy + lymph node sampling followed by abdominalradiotherapy, whole-lung radiotherapy, and regimen I
Diffuse anaplastic (preoperative treatment) 31% EFS 44% Preoperative treatment with regimen I followed by nephrectomy + lymph node sampling followed by abdominalradiotherapy, whole-lung radiotherapy
Stage V[12] Overall 61% EFS 80%
Favorable histology 65% 87% Bilateral renal biopsies and staging of each kidney followed by preoperative treatment with regimen EE-4A (if disease in both kidneys ≤ stage II) or regimen DD-4A (if disease in both kidneys > stage II), followed by second-look surgery and possibly more chemotherapy and/or radiotherapy
Focal anaplastic 76% 88% Bilateral renal biopsies and staging of each kidney followed by preoperative treatment with regimen I, followed by second-look surgery and possibly more chemotherapy and/or radiotherapy
Diffuse anaplastic 25% 42% Bilateral renal biopsies and staging of each kidney followed by preoperative treatment with regimen I, followed by second-look surgery and possibly more chemotherapy and/or radiotherapy

Risk factors[edit]

People of African descent[where?] have the highest rates of Wilms' tumor. Most instances of cancer occur among children between 3 to 3.5 years old.[citation needed] A genetic predisposition to Wilms' Tumor in individuals with aniridia has been established, due to deletions in the p13 band on chromosome 11.[13]

History[edit]

Dr. Sidney Farber, founder of Dana-Farber Cancer Institute, and his colleagues achieved the first remissions in Wilms' tumor in the 1950s. By employing the antibiotic actinomycin D in addition to surgery and radiation therapy, they boosted cure rates from 40 to 85 percent.

See also[edit]

References[edit]

  1. ^ EBSCO database verified by URAC; accessed from Mount Sinai Hospital, New York
  2. ^ WhoNamedIt.com: Max Wilms
  3. ^ Guaragna, M. S.; Soardi, Fernanda Caroline et al. (2010). "The Novel WT1 Gene Mutation p. H377N Associated to Denys-Drash Syndrome". Journal of Pediatric Hematology/Oncology 32 (6): 486–488. doi:10.1097/MPH.0b013e3181e5e20d. PMID 20562648. 
  4. ^ Stewenius, Y.; Jin, Y.; Øra, I.; De Kraker, J.; Bras, J.; Frigyesi, A.; Alumets, J.; Sandstedt, B.; Meeker, A. K.; Gisselsson, D. (2007). "Defective Chromosome Segregation and Telomere Dysfunction in Aggressive Wilms' Tumors". Clinical Cancer Research 13 (22): 6593–6602. doi:10.1158/1078-0432.CCR-07-1081. PMID 18006759.  edit, in turn citing Tournade, M. F.; Com-Nougué, C.; De Kraker, J.; Ludwig, R.; Rey, A.; Burgers, J. M.; Sandstedt, B.; Godzinski, J.; Carli, M.; Potter, R.; Zucker, J. M.; International Society of Pediatric Oncology Nephroblastoma Trial Study Committee (2001). "Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: Results of the Ninth International Society of Pediatric Oncology Wilms' Tumor Trial and Study". Journal of clinical oncology : official journal of the American Society of Clinical Oncology 19 (2): 488–500. PMID 11208843.  edit
  5. ^ Messahel, B.; Williams, R.; Ridolfi, A.; Warren, William et al. (2009). "Allele loss at 16q defines poorer prognosis Wilms tumour irrespective of treatment approach in the UKW1-3 clinical trials: a Children's Cancer and Leukaemia Group (CCLG) Study". Eur J Cancer 45 (5): 819–826. doi:10.1016/j.ejca.2009.01.005. PMID 19231157.  |first4= missing |last4= in Authors list (help)
  6. ^ Grundy, P. E.; Breslow, N. E.; Li, S.; Beckwith, JB et al. (2005). "Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group". J Clin Oncol 23 (29): 7312–7321. doi:10.1200/JCO.2005.01.2799. PMID 16129848.  |first4= missing |last4= in Authors list (help)
  7. ^ Call K, Glaser T, Ito C, Buckler A, Pelletier J, Haber D, Rose E, Kral A, Yeger H, Lewis W; Glaser; Ito; Buckler; Pelletier; Haber; Rose; Kral; Yeger; Lewis (1990). "Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus". Cell 60 (3): 509–20. doi:10.1016/0092-8674(90)90601-A. PMID 2154335. 
  8. ^ Huff V (1998). "Wilms tumor genetics". Am J Med Genet 79 (4): 260–7. doi:10.1002/(SICI)1096-8628(19981002)79:4<260::AID-AJMG6>3.0.CO;2-Q. PMID 9781905. 
  9. ^ Maiti S, Alam R, Amos CI, Huff V; Alam; Amos; Huff (2000). "Frequent association of beta-catenin and WT1 mutations in Wilms tumors". Cancer Res 60 (22): 6288–92. PMID 11103785. 
  10. ^ 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; Kim; Wells; Driscoll; Brannigan; Han; Kim; Feinberg; Gerald; Vargas; Chin; Iafrate; Bell; Haber (2007). "An X chromosome gene, WTX, is commonly inactivated in Wilms tumor". Science 315 (5812): 642–5. doi:10.1126/science.1137509. PMID 17204608. 
  11. ^ Ruteshouser EC, Robinson SM, Huff V; Robinson; Huff (June 2008). "Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors". Genes Chromosomes Cancer 47 (6): 461–70. doi:10.1002/gcc.20553. PMID 18311776. 
  12. ^ a b c d e f g h i j Unless otherwise specified in boxes, then reference is: Treatment of Wilms Tumor at National Cancer Institute. Last Modified: 03/29/2012
  13. ^ Pritchard-Jones, et al. Nature 346: 194-197, July, 1990.

External links[edit]