Wilms' tumor, Wilms tumor, or nephroblastoma is a cancer of the
kidneys that typically occurs in children, rarely in adults. It is named
after Dr Max Wilms, the German surgeon who first described it.
Approximately 500 cases are diagnosed in the U.S. annually. The majority occur in
otherwise normal children; a minority are associated with other developmental
abnormalities. It is highly responsive to treatment, with about 90% of patients
surviving at least five years. Signs and symptoms
Typical symptoms are: an abnormally large abdomen
abdominal pain fever
nausea and vomiting blood in the urine
high blood pressure in some cases Pathogenesis
Most nephroblastomas are unilateral, being bilateral in less than 5% of
cases, although patients with Denys-Drash syndrome mostly have
bilateral or multiple tumors. 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: 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. Dysfunction is caused when the tumor compresses the normal kidney
parenchyma. The mesenchymal component may include
cells showing rhabdomyoid differentiation or malignancy.
Wilms' tumors may be separated into 2 prognostic groups based on pathologic
characteristics: Favorable - Contains well developed
components mentioned above Anaplastic - Contains diffuse anaplasia
= Molecular biology= Mutations of the WT1 gene on chromosome
11p13 are observed in approximately 20% of Wilms' tumors. At least half of the
Wilms' tumors with mutations in WT1 also carry mutations in CTNNB1, the gene
encoding the proto-oncogene beta-catenin.
A gene on the X chromosome, WTX, is inactivated in up to 30% of Wilms' tumor
cases, according to research published in 2007.
Most cases do not have mutations in any of these genes.
Diagnosis 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.
Staging 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=
Stage 1 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
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 2
For Stage 2 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
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 Stage IV Wilms' tumor is defined as the
presence of hematogenous metastases, or lymph node relmetastases outside the
abdomenopelvic region. Stage V
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 on the
basis of extent of disease prior to biopsy.
Prognosis The overall 5-year survival is estimated
to be approximately 90%, 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
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. Genome-wide copy number and LOH status can be assessed
with virtual karyotyping of tumor cells. 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. Epidemiology
People of African descent have the highest rates of Wilms' tumor. Most
instances of cancer occur among children between 3 to 3.5 years old. A genetic
predisposition to Wilms' Tumor in individuals with aniridia has been
established, due to deletions in the p13 band on chromosome 11.
History 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
Beckwith-Wiedemann syndrome Denys-Drash syndrome
Hemihypertrophy National Wilms Tumor Study Group
Virtual Karyotype for 1p and 16q LOH WAGR syndrome
Perlman syndrome References
External links GeneReviewsNIH/UW entry on Wilms Tumor
Overview Information from National Cancer
Institute Wilms' tumor at DMOZ
Cancer.Net Wilms Tumor - Childhood