Wilms' tumor
Encyclopedia
Wilms' tumor or nephroblastoma is cancer
of the kidney
s that typically occurs in child
ren, rarely in adult
s.
Its common name is an eponym
, referring to Dr. Max Wilms
, the German surgeon (1867–1918) who first described this kind of tumor.
Approximately 500 cases are diagnosed in the U.S. annually. The majority (75%) occurs 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.
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 (rhabdomyosarcoma
tous Wilms).
Wilms' tumors may be separated into 2 prognostic groups based on pathologic characteristics:
is done. 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.
of tumor cells (fresh or paraffin-embedded). The overall prognosis with surgical removal is positive. Early removal tends to promote positive outcomes.
gene on chromosome 11 p 13 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.
Treatment: Nephrectomy
+/- 18 weeks of chemotherapy
depending on age of patient and weight of tumor. EG: less than 2 years old and less than 550g only requires Nephrectomy with observation
Outcome: 98% 4-year survival; 85% 4-year survival if anaplastic
Treatment: Nephrectomy + abdominal radiation + 24 weeks of chemotherapy
Outcome: 96% 4-year survival; 70% 4-year survival if anaplastic
Treatment: Abdominal radiation + 24 weeks of chemotherapy + nephrectomy after tumor shrinkage
Outcome: 95% 4-year survival; 56% 4-year survival if anaplastic
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
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 therapy based on tumor burden
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.
). During the operation, the surgeon checks if the other kidney has a tumor. If there are tumors in both kidneys, a piece of the tumor will be removed. After the surgery, the child is given some chemotherapy drugs like antinomicin D, vincristine, or doxorubicin.
Children 16 years old or older have higher mortality rates within their stages. This is due to them being treated less aggressively and consistently.
Adjuvant chemotherapy is sometimes used.
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
of the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s that typically occurs in child
Child
Biologically, a child is generally a human between the stages of birth and puberty. Some vernacular definitions of a child include the fetus, as being an unborn child. The legal definition of "child" generally refers to a minor, otherwise known as a person younger than the age of majority...
ren, rarely in adult
Adult
An adult is a human being or living organism that is of relatively mature age, typically associated with sexual maturity and the attainment of reproductive age....
s.
Its common name is an eponym
Eponym
An eponym is the name of a person or thing, whether real or fictitious, after which a particular place, tribe, era, discovery, or other item is named or thought to be named...
, referring to Dr. Max Wilms
Max Wilms
Carl Max Wilhelm Wilms was a German pathologist and surgeon who was a native of Hünshoven, which today is part of the town Geilenkirchen....
, the German surgeon (1867–1918) who first described this kind of tumor.
Approximately 500 cases are diagnosed in the U.S. annually. The majority (75%) occurs 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.
Pathology
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:
- blastemaBlastemaA blastema is a mass of cells capable of growth and regeneration into organs or body parts. Historically blastema have been thought to be composed of undifferentiated pluripotent cells, but recent research indicates that in some organisms blastema may retain memory of tissue origin...
- mesenchymeMesenchymeMesenchyme, or mesenchymal connective tissue, is a type of undifferentiated loose connective tissue that is derived mostly from mesoderm, although some are derived from other germ layers; e.g. some mesenchyme is derived from neural crest cells and thus originates from the ectoderm...
- epitheliumEpitheliumEpithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
Wilms' tumor is a malignant tumor containing metanephric blastema
Metanephric blastema
The metanephrogenic blastema or metanephric blastema is one of the two embryological structures that give rise to the kidney...
, 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
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
, cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
, bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
, 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 (rhabdomyosarcoma
Rhabdomyosarcoma
A rhabdomyosarcoma is a type of cancer, specifically a sarcoma , in which the cancer cells are thought to arise from skeletal muscle progenitors. It can also be found attached to muscle tissue, wrapped around intestines, or in any anatomic location...
tous 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
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
Diagnosis
The first sign is normally a painless abdominal tumor that can be easily felt by the doctor. An Ultrasound, Computed Tomography, or MRI are done first. Once a kidney tumor is found, a surgical biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
is done. 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.
Prognosis
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. Genome-wide copy number and LOH status can be assessed with virtual karyotypingVirtual Karyotype
Virtual karyotype detects genomic copy number variations at a higher resolution level than conventional karyotyping or chromosome-based comparative genomic hybridization .-Background:...
of tumor cells (fresh or paraffin-embedded). The overall prognosis with surgical removal is positive. Early removal tends to promote positive outcomes.
Molecular biology
Mutations of the WT1WT1
Wilms tumor protein is a protein that in humans is encoded by the WT1 gene.- Function :This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich DNA-binding domain at the N-terminus...
gene on chromosome 11 p 13 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
Beta-catenin
Beta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...
.
A gene on the X chromosome, WTX
FAM123B
FAM123B is a human gene.It has been associated with Wilms tumor....
, 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.
Staging and treatment
Staging is determined by combination of imaging studies and pathology 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 extrarenal or renal sinus lymph-vascular spaces
- No residual tumor apparent beyond the margins of excision.
- Metastasis of tumor to lymph nodes not identified.
Treatment: Nephrectomy
Nephrectomy
Nephrectomy is the surgical removal of a kidney.-History:The first successful nephrectomy was performed by the German surgeon Gustav Simon on August 2, 1869 in Heidelberg. Simon practiced the operation beforehand in animal experiments...
+/- 18 weeks of chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
depending on age of patient and weight of tumor. EG: less than 2 years old and less than 550g only requires Nephrectomy with observation
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.
- Extensive tumor involvement of renal sinus soft tissue.
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.
- Tumor is present at 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 therapy 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
In general, this type of cancer is curable. If the tumor is only in the kidney (typical), it can be removed along with the whole kidney (a nephrectomyNephrectomy
Nephrectomy is the surgical removal of a kidney.-History:The first successful nephrectomy was performed by the German surgeon Gustav Simon on August 2, 1869 in Heidelberg. Simon practiced the operation beforehand in animal experiments...
). During the operation, the surgeon checks if the other kidney has a tumor. If there are tumors in both kidneys, a piece of the tumor will be removed. After the surgery, the child is given some chemotherapy drugs like antinomicin D, vincristine, or doxorubicin.
Children 16 years old or older have higher mortality rates within their stages. This is due to them being treated less aggressively and consistently.
Adjuvant chemotherapy is sometimes used.
Risk factors
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.See also
- Beckwith-Wiedemann syndromeBeckwith-Wiedemann syndromeBeckwith–Wiedemann syndrome is an overgrowth disorder usually present at birth characterized by an increased risk of childhood cancer and certain congenital features. Originally, Dr...
- Denys-Drash syndromeDenys-Drash syndromeDenys-Drash syndrome is a syndrome characterized by the following conditions:* gonadal dysgenesis* nephropathy* Wilms tumorDenys-Drash Syndrome is a very rare disorder.- Etiology :...
- HemihypertrophyHemihypertrophyHemihypertrophy is a condition in which one side of the body or a part of one side is larger than the other. Children with hemihypertrophy have an increased risk of developing certain types of cancer, including Wilms tumor and liver cancer...
- National Wilms Tumor Study GroupNational Wilms Tumor Study GroupThe National Wilms Tumor Study Group is a cancer research cooperative group in the United States formed to study a type of kidney tumor that affects children called Wilms' tumor. In 2001, NWTS merged with several other pediatric oncology cooperative groups to create the Children's Oncology Group...
(NWTS) - Virtual KaryotypeVirtual KaryotypeVirtual karyotype detects genomic copy number variations at a higher resolution level than conventional karyotyping or chromosome-based comparative genomic hybridization .-Background:...
for 1p and 16q LOH - WAGR syndromeWAGR syndromeWAGR syndrome is a rare genetic syndrome in which affected children are predisposed to develop Wilms tumour , Aniridia , Genitourinary anomalies, and mental Retardation...
- Perlman syndromePerlman syndromePerlman syndrome is a rare overgrowth disorder present at birth. It is characterized by polyhydramnios and fetal overgrowth, including macrocephaly, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for Wilms' tumor at an early age...
External links
- GeneReviews/NCBI/NIH/UW entry on Wilms Tumor Overview
- Information from National Cancer InstituteNational Cancer InstituteThe National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...