INDIVIDUALS AT HIGH RISK FOR WILMS TUMOR
1. Overgrowth Syndrome The most common disorders in the overgrowth category are Beckwith-Wiedemann syndrome and isolated hemihypertrophy. A. Beckwith-Wiedemann Syndrome Beckwith-Wiedemann Syndrome (BWS) is characterized by pre and postnatal overgrowth, omphalocele, macro-glossia, nephromegaly and ear lobe creases. Somatic hemihypertrophy may or may not be present. While 80% of BWS cases are sporadic, 20% show a complex familial inheritance pattern explained by alteration of genes at 11P15. For BWS in general, over-expression of the insulin-like growth factor II gene located at 11P15 is believed to cause the characteristic overgrowth and perhaps confer increased risk of Wilms tumor. The overall risk of neoplasia with BWS may approach about 8%, and specifically the Wilms tumor risk appears to be in the range of 3-5%. B. Isolated Hemihypertrophy Unlike BWS, isolated hemihypertrophy is usually not hereditary, but this condition still confers an increased risk for the development of Wilms tumor. 2. Non-Overgrowth Syndromes This group is important because of the high incidence of
genital anomalies requiring surgical correction in this group. The WAGR
syndrome is a rare disorder characterized by a 30% risk for Wilms tumor,
aniridia, genital anomalies (such as undescended testicles and hypospadias)
and mental retardation. The Denys-Drash syndrome (DDS) is a related
disorder with more severe genital phenotype such as streak gonads,
penoscrotal hypospadias, "sex reversal" in XY individuals or
normal genitalia in XX individuals, renal failure due to glomerular
sclerosis, and an 80% of chance of Wilms tumor risk, often bilateral. FOLLOW UP Once identified, the child at high risk for Wilms tumor should be periodically screened with abdominal ultrasound. Surveillance of children at increased risk for Wilms
tumor is pursued aggressively through 3-monthly abdominal ultrasounds for
the first 8 years or so of their lives, as this is the usual period at
which the tumor appears. Three-monthly ultrasounds are necessary because
Wilms tumor can grow very rapidly and achieve enormous size within 6
months. MARKERS IN SCREENING FOR
WILMS TUMOR 1. Hypertension (Renin and Prorenin) While the incidence of hypertension in Wilms tumor is generally estimated to be about 25%, its use as a specific marker for Wilms tumor is limited by the fact that many childhood disorders can result in hypertension. Surprisingly, the etiology of hypertension in Wilms tumor still needs to be determined. It is also clear that other childhood malignancies may present with elevated levels of renin, prorenin or both. 2. Erythrocytosis (Erythropoietin) This hormone is synthesized primarily in the kidney by cells in and/or around the proximal tubules and acts on late progenitor cells in the bone marrow as a feedback signal to maintain the normal red blood cell mass optimal for oxygen transport in response to tissue hypoxia. However, erythrocytosis is not present in the majority of patients with Wilms tumor even though the incidence of erythropoietin activity is greater; and the reason for this is not known. 3. Acquired Von Willebrand's Disease About 5-10% of Wilms tumors will be affected by this problem. 4. Insulin Growth Factor Insulin growth factors I and II are growth-promoting polypeptides associated with specific binding proteins which may modulate their action. A number of patients with Wilms tumor have elevated insulin growth factor binding protein-2 compared with normal controls. 5. Hyaluronic Acid Products This molecule is present in many embryonic tissues and is
prominent whenever rapid tissue turnover occurs. Urinary levels of
hyaluronic acid, hyaluronic acid stimulating activity (a glycoprotein) and
hyaluronidase have been found in children with Wilms tumor. MULTICYSTIC DYSPLASTIC
KIDNEYS Wilms tumor usually arises from abnormal remnants of developmentally immature nephrogenic cells in the postnatal kidney which are termed "nephrogenic rests" or "nodular renal blastema." Because these abnormal cell remnants are present in 20-40% of kidneys resected for Wilms tumor and because these same remnants have been found in kidneys with multicystic dysplasia (MCD) and in the kidneys of infants and children with congenital obstructive uropathy, it was suggested that multicystic dysplastic kidneys should be resected to prevent the possibility of Wilms tumor formation. However, 0.01% of live-born infants are destined to develop a Wilms tumor. On the other hand, these primitive nephrogenic rests that may predispose to tumor formation are much more numerous in younger infants than in older ones, suggesting that many of these rests disappear spontaneously. Therefore, the majority of these primitive nephrogenic rests do not give rise to Wilms tumor, and most of them involute spontaneously without forming tumors. In part, this may be because nephrogenic rests appear to be of two types: (a) perilobar, commonly found in routine autopsies with little likelihood of giving rise to Wilms tumor, or (b) intralobar, which carry a high risk. Studies reviewing the incidence of Wilms tumor in
severely dysplastic and congenitally obstructed kidneys show that the risk
for developing Wilms tumors is close to that of the general population,
and therefore the risk seems too low to justify routine nephrectomy in
children with multicystic dysplasia or congenitally obstructed kidneys
unless other urological/ medical conditions apply. SCREENING CRYPTORCHID BOYS
AND INFERTILE MALES FOR TESTIS TUMORS Boys with undescended testes have about a 4-fold
increased risk of subsequently developing testicular cancer. However, this
pertains more to those with intra-abdominal undescended testicles.
Intratubular germ neoplasia has been found in about 23% of undescended
testes. Testicular intratubular neoplasia (TIN) has been recognized as a
precursor to testicular germ cell tumors. Seminoma is the usual type of
tumor that develops in cryptorchidism and infertile males, and its
incidence is significantly higher when compared with the normal
population. SCREENING FOR
NEUROBLASTOMA IN INFANTS Neuroblastoma is the most frequent and least curable cancer in infants. Only about 20% of children are cured. VMA (vanillylmandalic acid) and HVA (homovanillic acid) can be found in the urine of 85% of affected patients. A study using these urinary markers to screen for neuroblastoma has demonstrated that a screening at 3 weeks and 6 months of age does not make a difference in the incidence of advanced stage disease in children over one year of age. Neuroblastoma is a unique disease that may undergo spontaneous maturation, particularly in younger infants. That screening for neuroblastoma does not appear beneficial suggests that some of these tumors are either undetectable by the screening, arise after the age of screening, or exhibit rapid growth and spread. SCREENING OTHER ANOMALIES WITH POSSIBLE RISK FOR MALIGNANCY 1. Horseshoe Kidneys The claim for increased risk of adenocarcinoma or transitional cell carcinoma of the kidney has not been substantiated for this developmental anomaly. 2. Megaureter In this anomaly, there may be an increased risk for transitional cell carcinoma developing (usually in the mid third ureter). 3. Ureteral stumps There may be some malignant potential for transitional cell carcinoma development in ureteral stumps after nephrectomy and partial ureterectomy. 4. Vesicoureteral reflux Patients with bladder carcinoma and vesicoureteral reflux have a 15-fold greater incidence of ureteral or renal carcinoma than non-refluxers. 5. Urinary diversion
6. Exstrophy The untreated exstrophy bladder has about a 4% chance of developing a carcinoma, usually adenocarcinoma, probably resulting from chronic urinary infections. 7. Intersex
8. Bilharzia In the Middle East, the rate of schistosoma infection in boys in endemic areas is high and may lead to carcinoma of the bladder, usually squamous, in young adults. 9. Radiation Abdominal or retroperitoneal external beam radiation may increase the chance for developing carcinoma of the kidney.
|
||