Wilms Tumor

Murali M. Chintagumpala

Wilms tumor is a malignant embryonal neoplasm of the kidney of mixed cellular histology. The incidence remains remarkably constant, with 8.1 cases per million white children younger than 15 years reported annually. Wilms tumor is diagnosed only slightly less often than neuroblastoma, and like neuroblastoma, it is a tumor of young children: Eighty percent of these tumors occur in children younger than 5 years, and more than 98% of cases present by 7 years. The incidence peaks in children between the ages 3 and 4 years, with a median of 42 months for girls and 35 months for boys with unilateral disease. The tumors associated with congenital anomalies and synchronous bilateral tumors occur at an earlier age. Worldwide, the gender ratio is close to 1:1, but in the United States, the rate of unilateral tumor in girls is 22% higher than in boys.

ETIOLOGY

Wilms tumor occurs in hereditary and nonhereditary forms. The hereditary form is autosomal dominant, may be multifocal in presentation, and may be associated with other congenital anomalies. Tumors in multiple family members have been reported but are extremely rare.

A variety of congenital abnormalities can occur in association with Wilms tumor. Children with Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation (WAGR syndrome) have a constitutional deletion at chromosome 11p13, where the Wilms tumor gene WT1 has been located. These patients have a 30% probability of developing Wilms tumor. A second Wilms tumor gene (WT2), located at 11p15.5, was strongly suggested by tumor-specific loss of heterozygosity and linkage studies in familial Beckwith-Wiedemann syndrome, which is characterized by gigantism and macroglossia. The risk of developing Wilms tumor in Beckwith-Wiedemann syndrome is in the range of 3% to 5%.

Most patients with sporadic isolated aniridia have some degree of 11p13 deletion with a significant risk of Wilms tumor. Isolated hemihypertrophy also is associated with an increased risk for the development of Wilms tumor. Other syndromes that have an increased risk for the development of Wilms tumor include Perlman syndrome, Sotos syndrome, and Denys-Drash syndrome. The most common genitourinary anomalies associated with Wilms tumor are hypoplasia, fusion and ectopia of
the kidney, duplications in the collecting systems, hypospadias, and cryptorchidism.

PATHOLOGY

Wilms tumor is thought to arise from abnormalities in the development of metanephric blastema. Persistent metanephric blastemal cells in the postnatal period are termed nephrogenic rests and are regarded as precursor lesions for Wilms tumor.

Histologically, the tumor is composed of mixed mesenchymal elements in different stages of maturity. Renal blastema denotes epithelial elements that form abortive or embryonic glomerulotubular structures. These structures appear in an undifferentiated stroma, which also may contain differentiated mesenchymal structures such as striated muscles, cartilage, adipose tissue, and bone. The tumors have been referred to so as to denote the involvement of blastemal, epithelial, and stromal elements. Individual tumors may have a monomorphic pattern that can be mistaken for a hamartoma.

The use of the terms favorable histology and unfavorable histology was derived from the National Wilms’ Tumor Study (NWTS). Initially, three types of unfavorable histology were identified, which accounted for 10% to 14% of all Wilms tumors and for more than 60% of mortality. These are as follows: focal or diffuse anaplastic tumors; clear cell sarcoma, often called the bone-metastasizing tumor; and rhabdoid tumor, which often metastasizes to the brain. The rhabdoid histologic type is a highly malignant tumor similar in structure to sarcomatous tumors that occur outside the kidney. This tumor and clear cell sarcoma are no longer considered Wilms tumor variants by the NWTS. They account for a small proportion of all tumors that have been registered as Wilms tumors but a disproportionately high percentage of the fatalities.

The classic, congenital mesoblastic nephroma is a benign tumor that sometimes resembles a clear cell sarcomatous form of Wilms tumor. Approximately 60% of these tumors are diagnosed in the first 3 months and 90% during the first year of life.

CLINICAL AND DIAGNOSTIC FEATURES

The classic Wilms tumor appears as a silent mass in the abdomen in almost two-thirds of patients. The tumor often is detected accidentally by the patient’s parents or incidentally during the course of a physical examination performed for other medical reasons. Abdominal pain occurs in approximately one-third of the patients. The mass is usually hard, smooth, and confined to the flank or one side of the abdomen. Occasionally, a patient with Wilms tumor experiences a sudden hemorrhage into the tumor and presents with rapid abdominal enlargement and anemia. Hematuria has been observed in 12% to 25% of patients, and hypertension has been reported in 25% of cases. Nonspecific symptoms such as fever, malaise, constipation, and anorexia may be reported, but weight loss is an uncommon association.

Only gold members can continue reading. Log In or Register to continue