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Nephroblastoma or Wilms tumor is the most common renal tumor of young children which develops from the residues of metanephric blastema. This type of tissue usually disappears before the 36th week of gestation. However, if parts of this embryonic tissue remain, this is called a nephroblastomatosis. The nephroblastomatosis is considered a tumor precursor and can be found in 40 % of children with Wilms tumor.
Incidence of Nephroblastoma
The incidence of Wilms tumor is 1 : 10,000. 85 % of patients are younger than 6 years. Usually, diagnosis is made in the second or third year of life. Girls are affected slightly more often than boys, and there is a different incidence for children of different ethnicities. For example, the incidence rate in Asia is substantially lower than in European or American children.
Causes of Nephroblastoma
The genesis of nephroblastoma is much more complex than that of some other malignant tumors in children. About one third of patients with nephroblastoma have mutations of the tumor suppressor gene WT1: a deletion of genetic material on the short arm of chromosome 11 . Other factors influencing tumor development are losses of heterozygosity and of genomic imprinting.
In 10 % of the cases, the tumor is associated with malformations such as the WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations, mental retardation), Denys-Drash syndrome (pseudohermaphroditism, glomerulopathy, Wilms tumor), von Recklinghausen disease (type 1 neurofibromatosis), and the Beckwith-Wiedemann syndrome (exomphalos-macroglossia-gigantism (EMG) syndrome).
Metastasis of Nephroblastoma
In 5 % of cases, the nephroblastoma are bilateral. Metastasis mostly occurs in regional lymph nodes and in the lungs.
Histological Classification of Nephroblastoma
The histological classification according to the SIOP (International Society of Pediatric Oncology) of 2002 distinguishes three groups of different degrees of malignancy. 80 % of cases can be classified as intermediate malignancy, i.e., the standard histological finding.
Typically, there are blastema present in the tumor, consisting of clusters of cells with hyperchromatic ovoid nuclei. In the blastema, different structures can be observed, including rosettes, tubules, and pseudoglomerular structures.
Symptoms of Nephroblastoma
The most common sign of nephroblastoma is a painless swelling of the abdomen. Only about 1/4 of the children complain of pain. In few cases, hematuria can be observed. Uncharacteristic symptoms include fever, constipation, diarrhea, and weight loss.
Approximately 10 % of nephroblastoma are discovered only incidentally during a check-up because they are mostly asympotmatic.
Radiological Examination of Suspected Nephroblastoma
Using sonography, CT or MRI scans, the dimensions of the tumor can be displayed and lymph node metastases can be detected. Also, a thrombus in the inferior vena cava can often be detected due to cone-shaped ingrowths of the tumor into the vessels. A urogram typically reveals that the tumor is spreading apart the pyelocaliceal system.
Imaging of the second kidney before surgery is crucial since a single kidney or bilateral tumors must be excluded.
Specific tumor markers do not exist for nephroblastoma. But the determination of catecholamine degradation products in serum may be useful in some cases for distinguishing a possible neuroblastoma.
Staging of Nephroblastoma
- Stage I: Tumor is limited to the kidney and completely resectable.
- Stage II: Tumor extends beyond the kidney but is completely resectable.
- Stage III: Tumor resection only partially possible, or lymph nodes are affected.
- Stage IV: Hematogenous metastases can be detected.
- Stage V: The nephroblastoma is bilateral.
Treatment of Nephroblastoma
The treatment of nephroblastoma depends on the stage of disease, histological subtype and the age of the child. Without treatment, the disease results in the death of patient. Surgical removal of the tumor always involves the risk of rupturing the tumor and seeding into the abdomen, with the subsequently worse prognosis. Therefore, only for children under 6 months of life is surgery the primary treatment. For older children, the reduction of the tumor mass using neoadjuvant chemotherapy is the first step, with the goal of reaching stage I before surgery. For tumor patients with stage III or higher, radiation therapy becomes necessary. In case of a unilateral nephroblastoma, tumor nephrectomy is then the next step.
Prognosis for Nephroblastoma
Prognosis is very good. The 5-year survival rate is 80 %; for stage I patients, it is even 90 %.
Follow-Up Surveillance and Aftercare
Still during on-going treatment, it is important to be aware of the possible presence of sinusoidal obstruction syndrome (formerly called veno-occlusive disease) affecting the small hepatic veins. It is a common side-effect of the cytostatic drug actinomycin D, which represents the key substance in the chemotherapy of nephroblastoma. For follow-up surveillance, abdominal sonography is a suitable method as it avoids any further radiation exposure.
Regular Aftercare of Nephroblastoma
For ruling out any lung metastases, it is imperative to periodically order x-ray images of the lung. In the long term, special attention has to be paid to any growth disturbances in the skeleton and soft tissues, which could be a possible consequence of radiation.
Popular Exam Questions on Nephroblastoma
Solutions can be found below the references.
1. During a regular check-up of a mature born baby, you notice an indolent swelling of the abdomen. The veins seem to be abormally prominent in the abdominal area. The mother explains that the baby suffers from constipation, to which she had attributed the swollen abdomen. In an abdominal ultrasound,you detect a large tumor at the right kidney which seems to be penetrating the renal vessels. Which of the following diagnostic tests is NOT indicated?
- Biopsy of the tumor and histological examination
- CT of the abdomen
- Urography for assessment of the pyelocaliceal system
- Sonographic representation of the 2nd kidney
- CT of the lung
2. Which malformation syndrome is not associated with nephroblastoma?
- Laurence-Moon syndrome
- Denys-Drash syndrome
- WAGR syndrome
- Beckwith-Wiedemann syndrome
- Von Recklinghausen disease
3. Which cytostatic substance frequently used in the chemotherapy of nephroblastoma can lead to the sinusoidal obstruction syndrome (veno-occlusive disease) when administered in overdose, especially in dystrophic children?
- Amphotericin B
- Actinomycin D