Wilms Tumor

At a Glance

Wilms tumor of the kidney, also known as a nephroblastoma, typically occurs in children 2-5 years of age, with 95% of tumors occurring before 10 years of age. It is the primary renal tumor of childhood, affecting 1 out of 10,000 children in the United States. Between 5 and 10% of cases involve both kidneys, either simultaneously or one after another.

Approximately 10% of cases in which children develop a Wilms tumor are associated with four varying types of congenital malformations. The WAGR syndrome is characterized by aniridia, genital anomalies, and mental retardation. Children with the WAGR syndrome have a 33% chance of developing a Wilms tumor.

In the Denys-Drash syndrome, typified by gonadal dysgenesis and early onset nephropathy (leading to renal failure), patients have a 90% chance of developing a Wilms tumor. These patients demonstrate an abnormality in the WT1 gene, which is a dominant-negative missense mutation in the zinc-finger region.

The third abnormality is the Beckwith-Wiedemann syndrome, which is characterized by organomegaly, macroglossia, hemihypertrophy, omphalocele, and abnormal large cells in the adrenal cortex. It operates under genomic imprinting (multiple genes that are expressed from only one parent).

Wilms tumor is typically discovered as a palpable mass, related to its enormous size. Patients often present with hematuria.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The diagnosis of a Wilms tumor is a tissue diagnosis.

Wilms tumors present as a large abdominal mass, often accompanied with hematuria and pain.

One should perform a urinalysis with microscopic to quantify the amount of hematuria and to rule out other diseases, such as infection (leukocytes and bacteria) or primary renal disease (casts).

One should send a urine sample for cytological examination and perform imaging studies.

Urine cultures are useful in establishing the presence of infection, as well as ruling it out.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Pseudohematuria can by caused by food, such as beets, or food dyes. It may be caused by certain medications, such as phenytoin, rifampin, or pyridium. Pigments, such as porphyria, myoglobin, or hemoglobin, will also appear as hematuria. The latter usually results from intravascular hemolysis.

In the renal parenchyma, postinfectious glomerulonephritis, thin basement membrane disease, IgA nephropathy, membranoproliferative glomerulonephritis, focal glomerulosclerosis, and crescentic glomerulonephritis all represent primary glomerular causes of hematuria.

Diabetes mellitus, lupus erythematosus, Goodpasture’s syndrome, polyarteritis nodosa, and endocarditis represent systemic causes of hematuria, as do hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, Henoch-Schonlein purpura, malignant hypertension, polycystic kidney disease, hereditary nephritis, and Fabry’s disease. Other causes of hematuria are acute pyelonephritis; nephrolithiasis; renal cyst; renal trauma; other urinary tract neoplasms in the kidneys, ureters, or bladder; low clotting factors; thrombocytopenia; acute interstitial nephritis; analgesic nephropathy; sickle cell trait or disease; medullary sponge kidney; malaria; papillary necrosis; and renal infarction.

Lower urinary tract abnormalities cause hematuria, such as cystitis, prostatitis, urethritis, trauma, foreign body calculi, varices, radiation cystitis, cyclophosphamide, anticoagulants, schistosomiasis, and tuberculosis. Nonurinary tract causes of hematuria include appendicitis and neoplasms of adjacent organs.

Interstitial nephritis can be caused by penicillins and cephalosporins, sulfonamides, sulfonamide-containing diuretics, NSAIDs, rifampin, phenytoin, and allopurinol. Although 95% of cases of interstitial nephritis present with hematuria, they also present with white cells in the urine and with white cell casts and are accompanied with fever, rash, arthralgias, and peripheral eosinophilia.

Proteinuria and protein casts suggest a renal origin. Bacteria in the urine and positive urine cultures suggest infectious causes. Further evaluation includes cytology, upper tract imaging, and cystoscopy.

What Lab Results Are Absolutely Confirmatory?

The typical Wilms tumor is a unicentric, spherical mass sharply demarcated from the renal parenchyma. Roughly 10% of such cases are multifocal in origin. Diagnosis is confirmed by microscopic tissue examination. Blood tests cannot make the diagnosis.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Patients with the WAGR syndrome carry germline deletions of 11p13. Two genes are located here: the PAX6 and WT1 gene. Patients with deletion of PAX6 only do not have an increased risk of developing a Wilms tumor. Only 10% of patients with a WT1 gene deletion develop a Wilms tumor.

The WT1 test is a histochemical test made from a formalin-fixed, paraffin-embedded tissue.

Other abnormalities have been associated with the Wilms tumor, such as von Willebrand factor, active and inactive renin, erythropoietin, and neuron-specific enolase, which may contribute to unusual presenting symptoms (coagulopathy, hypertension, and polycythemia). None of these should be used for screening, because they occur with such low frequency.