Wilms' tumor C64

In 1898, Max Wilms (1867 - 1918) was the first to describe the Wilms tumor, which was named after him both nationally and internationally (Siewert 2001).

Wilms' tumor (WTU) is a highly malignant new embryonic formation of the kidney (Siewert 2001).

STI is the most common neoplasia in children, accounting for 7.5% of all malignant tumours. The incidence is 1: 100,000.

Usually the tumour occurs unilaterally, but in 5 % - 10 % it can also occur bilaterally and is then often more common in families (Herold 2020 / Graf 2016 / Siewert 2001). There are clear ethnic differences: in Asia the tumour occurs less frequently than in Europe and the USA, but it is much more common in African-Americans (von Schweinitz 2009).

Associated malformations:

Children with a nephroblastoma have an above average incidence of the following additional malformations:

• Aniridia (malposition of the iris [Reinhardt 2014])
• Beckwith- Wiedemann syndrome (large growth syndrome [Mayatepek 2019])
• different urogenital or renal malformations (Seeber 1993)

Tumor triggering factors are not known. Bilateral tumours are usually inherited in an autosomal dominant manner, unilateral tumours are very rare (Siewert 2001). In the meantime, 3 genes are known for Wilms' tumor (Herold 2020).

It is a dysontogenetic tumor consisting of undifferentiated cells of the metanephrogenic blastem (Herold 2020).

The tumour occurs preferentially between the ages of 3 - 4 years, with girls being affected slightly more frequently than boys. In rare cases, Wilms' tumor occurs in adulthood.

About 10% of children are completely asymptomatic. In another 10%, the tumor is discovered in the course of screening.

Otherwise, the following symptoms may exist:

• abdominal pain
• loss of appetite
• vomiting
• possibly fever
• haematuria (in case of invasion of the renal pelvis)
• Hypertension (exists in about 10%-20% of patients; in other renal tumors in up to 50% of cases) (Herold 2020 / Graf 2016 / v. Schweinitz 2009)

Inspection and palpation

• indolent swelling in the tumor area (Graf 2016)
• distension of the abdomen

Tumour biopsy: In the case of clear imaging procedures, a preoperative biopsy is not necessary in children > 6 years and < 16 years of age (Graf 2016).

Sonography

• Representation of the tumor
• Exclusion or detection of possible metastases
• Doppler sonographic evaluation of the renal vein and the inferior vena cava up to the right atrium to exclude tumor thrombi (Graf 2016)

Echocardiography: Echocardiography should be performed before and after cardiotoxic chemotherapy (Graf 2016).

CT: A thoracic CT to exclude pulmonary metastases is mandatory (Graf 2016).

MRI: In abdominal MRI the tumor volumetry can be calculated according to the ellipsoid formula (Count 2016).

Angiography: This shows

• a hypervascularization of the tumor
• dilated, tortuous vessels
• small arterial aneurysms
• Blood Lakes
• abdominal presentation of the aorta (possible displacement by the tumour) (Schild 1994).

Certain tumour markers are not known.

It is recommended to determine the WT1 germ line status (Wilms tumor gene1), as the risk of severe renal failure is increased in these patients (Graf 2016).

Wilms' tumor is a mixed tumor that consists of different structures:

• glandular parts
• renal embryonic blasts
• immature muscular or connective tissue
• Fat content

Due to the rapid growth of tumours, extensive necrosis is often found. The origin from the kidney can often hardly be identified due to the immaturity of the tissue (Lentze 2007).

Histologically one differentiates between 12 different subtypes with 3 degrees of malignancy:

• low
• intermediary
• high (Graf 2016 / Lentze 2007)

The histological staging of the nephroblastoma is performed according to SIOP (Internationale d'Oncologie Pédiatrique):

• Stage I: The tumour is limited to the kidney and can be completely removed. The capsule of the tumour is not exceeded.
• Stage II: The tumour exceeds the capsule but can be completely removed. The lymph nodes are not affected.
• Stage III: There is an infestation of regional lymph nodes. There are no hematogenic metastases. The tumour can only be removed incompletely.
• Stage IV: There are distant metastases, particularly in the lungs, liver, bones and brain.
• Stage V: This is a bilateral nephroblastoma (Graf 2016).

(rare) renal tumors (in 50 % of the cases there is a hypertonus, in the case of the Wilms tumor only in 10 % - 20 %) such as:

• Rhabdoid tumor
• mesoblastic nephroma
• renal cell carcinoma

or (rare) non-malignant tumours such as:

• Teratoma
• cystic nephroma
• hamartoma (v. Schweinitz 2009)

The treatment is interdisciplinary and can include: surgery, chemotherapy, radiotherapy, resection of solid metastases (Herold 2020).

The necessity of radiotherapy should be decided individually.

Indications for radiotherapy are:

• for intermediate malignancy: local stage III
• with high malignancy: from stage II (Graf 2016)

Radiation therapy can also be used for lung metastases (Graf 2016).

Chemotherapy

The GPOH (Society for Pediatric Oncology and Hematology) and SIOP (International Society of Pediatric Oncology) recommend preoperative combined chemotherapy in children > 6 months and < 16 years.

(Count 2016)

Preoperatively, bilateral infestation should be safely excluded.

The surgical procedure is usually elective and in the case of unilateral nephroblastoma includes a radical tumor nephrectomy.

In the case of bilateral involvement, the procedure should be decided on individually and, if possible, kidney preserving surgery should be performed.

(Count 2016)

The prognosis of a nephroblastoma is infaust without treatment, with appropriate therapy good (Graf 2016). The survival rate depending on the stage of the disease and the histology:

• Stage I:
  • low malignancy: 95%.
  • Intermediate malignancy: 92 %
  • high malignancy: 85
  • total: 91 %
• Stage II:
  • low malignancy: 100
  • Intermediate malignancy: 90
  • high malignancy: 76 %
  • total: 88 %
• Stage III:
  • low malignancy: 100
  • Intermediate malignancy: 85
  • high malignancy: 67 %
  • total: 82 %
• Stage IV:
  • low malignancy: 92 %
  • Intermediate malignancy: 73 %
  • high malignancy: 36 %
  • total: 70 %
• Stage V:
  • low malignancy: 95
  • intermediate malignancy: 87 %
  • high malignancy: 69 %
  • Total: 85 % (Michel 2016)

1. Graf N et al. (2016) S 1 Guideline Nephroblastoma (Wilms' tumor) AWMF- Register 025 / 004 Class S1
2. Herold G et al (2020) Internal medicine. Herold Publishing House 656
3. Lentze M J et al (2007) Paediatrics: Principles and practice. Springer Publishing House 1325
4. Mayatepek E (2019) Pediatrics: Basics, Clinic and Practice. Urban and Fischer publishing house 69
5. Michel M S et al (2016) The urologist: retroperitoneum, kidney, bladder, urethra, tumor therapy. Springer Publishing House 2025 - 2035
6. Reinhardt D et al (2014) Therapy of diseases in childhood and adolescence. Springer publishing house 1128
7. Schild H et al (1994) Reference Series Radiology: Angiography. Thieme publishing house 191
8. von Schweinitz D et al (2009) Pediatric Surgery: Visceral and General Surgery in Children. Springer publishing house 559 - 570
9. Seeber S et al (1993) Therapeutic Concepts Oncology. Springer Publishing House 358
10. Siewert R et al (2001) Practice of Visceral Surgery: Oncological Surgery. Springer Publishing House 824 - 832