4.2.4Nephroblastomatosis

•The fetal kidney is formed by the development of nephrons from fetal metanephric blastema surrounding the ureteric bud.

•The fetal renal tissue matures into normal renal parenchyma during gestation, but, occasionally, fetal tissue persists into infancy as

microscopic foci called nephrogenic rests (renal blastema).

•Renal blastema and nephroblastomatosis are interrelated conditions closely related to Wilms tumors (Figs. 4.13 and 4.14).

•The persistence of primitive renal blastema beyond 4 months of age is abnormal except in small microscopic rests.

•Nephroblastomatosis is defined as the presence of multifocal nephrogenic rests.

•Nephrogenic rests are foci of metanephric blastema that persist beyond 36 weeks gestation and have the potential for malignant transformation into Wilms’ tumor.

•Nephrogenic rest are found incidentally in 1 % of infants.

•It is currently believed that nephrogenic rests give rise to approximately 30–40 % of Wilms’ tumors.

•Nephrogenic rests are found in up to 99 % of bilateral Wilms’ tumors.

•Nephrogenic rests are classified histologically as:

–Dormant, sclerosing, hyperplastic, or neoplastic.

–Dormant and sclerosing rests are usually microscopic and are not considered to have malignant potential.

–Hyperplastic and neoplastic rests are grossly visible as small tan nodules surrounded by normal parenchyma.

•There are two pathologic subtypes of nephrogenic rest based on location (perilobar and intralobar):

–Perilobar rest (90 %)

–Intralobar rest (10 %). This is more associated with Wilms’ tumor.

–Prilobar rests:

• They are found in subcapsular location

with well demarcated low power margins.

•They are associated with Beck-with- Wiedemann syndrome and hemihypertrophy, Perlman syndrome (visceromegaly, gigantism, cryptorchidism, polyhydramnios, characteristic facies), and trisomy 18.

•Malignant degeneration into Wilms tumor is most common in patients with Beckwith-Wiedemann syndrome and hemi-hypertrophy, occurring in 3 % of cases.

–Intralobar rests:

•These are considerably less common than the perilobar nephrogenic rest.

•They present anywhere within the kidney and often have a more irregular and intermixed margins.

•They have a higher association with Wilms tumor development.

•These rests are found in 78 % of patients with Denys-Drash syndrome and nearly 100 % of patients with sporadic aniridia and are also seen in patients with WAGR syndrome.

–Ultrasonographic detection of these rests is possible, but sonography lacks the sensitivity of CT and MRI.

–On CT, macroscopic nephrogenic rests appear as low-attenuation peripheral nodules

with poor enhancement relative to that of adjacent normal renal parenchyma.

–On MRI, the nodules demonstrate low- signal-intensity foci on both T1-weighted and T2-weighted images.

–On sonograms, the affected kidney may be enlarged and lobulated with multiple hypoechoic areas. Corticomedullary differentiation may be lost.

–After such findings are discovered, three monthly ultrasound examinations should be performed to detect their progression to a Wilms’ tumor.

–Lymphoma can mimic the appearance of nephroblastomatosis but is unusual in infants and young children.

•Treatment for nephrogenic rests:

–This is controversial.

–Some investigators recommend chemotherapy, whereas others maintain that close serial radiologic evaluation of enlarging masses is sufficient.

–Screening for Wilms tumor in patients with syndromes associated with nephrogenic rests should be performed.

–Ultrasound is a good follow-up investigation, cheap, readily available and can be done easily without anesthesia, however CT-scan is the method of choice for follow-up.

–On imaging, nephroblastomatosis appear as discrete, homogeneous, non-enhancing renal masses.

–Any rapid growth, inhomogeneity, or heterogeneous enhancement should be taken seriously and worrisome for development of Wilms.

4.2.5Clinical Features

•The usual presentation of Wims’ tumor is with a painless abdominal mass discovered accidently by the parents or by a physician during a routine physical examination. It is not uncommon for the mother to discover the mass while giving bath to her child. This is the presentation in more than 80% of children with Wilms tumor.

•The mass is discovered after coincidental trauma in up to 10 % of cases.

•Abdominal pain (25 %)

•Wilms’ tumor can present with (Figs. 4.15, 4.16, 4.17, and 4.18):

–Abdominal swelling or distension

–Abdominal mass

–Abdominal pain

–Fever

–Nausea and vomiting

–Hematuria

–Hypertension

–Urinary tract infection

–Wilms’ tumor can grow rapidly as a result of bleeding into the tumor or from actual tumor growth.

–Bleeding into the tumor will lead to anemia and if severe will result in heart failure.

•Hematuria:

–May be seen in 10–15 % of cases.

–This can be microscopic or gross hematuria.

–This is seen often after a relatively minor trauma and injury of the enlarged kidney by the tumor.

–Hematuria may be seen as a late presentation that is usually associated with tumor invasion of the calyces and considered a bad prognostic sign.

•Hypertension:

–As many as one third of patients with Wilms tumor present with hypertension. Their blood pressure usually normalizes after nephrectomy, but they occasionally require prolonged therapeutic intervention

–Increased blood pressure may be present in 20 % of Wilms’ tumor cases.

–Hypertension in Wilms’s tumor results from pressure effect of the tumor on the renal vessels leading to increased secretion of rennin.

•Rarely, the tumor may produce erythropoietin leading to increased red blood cells production and polycythemia.

•Patients with Wilms tumor can present with hemorrhage into their tumor leading to hypotension, anemia, and fever.

•Rarely patients with Wilms tumor and lung metastases may present with respiratory symptoms.

•Wilms’ tumor can occur as part of rare genetic syndromes, including: