V. Management

A. Surgery

Localized disease is managed primarily by surgical resection. For metastatic disease, biopsy or excision of the primary tumor is important for N-myc gene assessment. Complete resection is usually delayed until after chemotherapy is administered but may be done at the time of diagnosis.

B. RT

RT is used for bulky tumor in combination with chemotherapy and as part of the conditioning regimen for BMT.

C. Chemotherapy

1. Residual localized or advanced disease. Aggressive multimodal chemotherapy with Adriamycin, cyclophosphamide, etoposide, and cisplatin combined with surgical resection and BMT has improved survival in stage III and IV disease.

2. Congenital disease. In patients with congenital disease, specifically for stage IVS, chemotherapy is not used unless the tumor causes significant symptoms.

D. BMT

BMT (usually autologous) following intensive radiation and chemotherapy appears to improve the outlook for patients with advanced disease.

Wilms' tumor (nephroblastoma)

I. Epidemiology and etiology

A. Incidence

Wilms' tumor most frequently affects children between one and five years of age, and rarely those more than eight years of age. The incidence is about seven per million in the childhood age group. Familial clusters have been described, particularly in patients with bilateral Wilms' tumors.

B. Associated abnormalities

Wilms' tumor has been associated with certain congenital anomalies including genitourinary anomalies, aniridia (absence of an iris), and hemihypertrophy (Beckwith-Wiedemann syndrome). Deletion of the short arm of chromosome 11 has been associated with a syndrome of Wilms' tumor, mental retardation, microcephaly, bilateral aniridia, and ambiguous genitalia.

II. Pathology and natural history

A. Histopathologic classification

Histopathologic classification most accurately predicts the prognosis.

1. Wilms' tumor. Tumors that display mature elements and few anaplastic cells have the most favorable prognosis and are termed "favorable" histology. "Unfavorable" histology concerns tumors that have focal or diffuse anaplasia, rhabdoid sarcoma, or clear cell sarcoma. Unfavorable histology accounts for 12 percent of Wilms' tumors but almost 90 percent of deaths.

2. Congenital mesoblastic nephroma is a rare benign tumor that is common in infancy (the most common renal neoplasm during the first month of life) and can be histologically confused with Wilms' tumor. This tumor consists of spindle-shaped, immature connective tissue cells that have a distinctive fibroblastic appearance with only minimal nuclear pleomorphism and mitoses.

B. Sites

Approximately 7 percent of Wilms' tumors are bilateral at the time of diagnosis.

C. Mode of spread

The lungs are the principal sites of metastases; liver and lymph nodes are the next most common sites. Bone marrow metastases are extremely rare and tend to be associated with clear cell subtypes of sarcomatous Wilms' tumor. CNS metastases are extremely rare.

D. Paraneoplastic syndromes

Wilms' tumors have been rarely associated with increased erythropoietin (erythrocytosis) and with increased renin (hypertension).