328 CHAPTER 6 Urological neoplasia

Wilms tumor and neuroblastoma

Wilms tumor

This is a rare childhood tumor, affecting 1 in 10,000 children. It represents 80% of all genitourinary tumors affecting children under age 15 years. Males and females are equally affected, with 20% being familial and 5% bilateral. Three-quarters of cases present under the age of 5 years. It is rarely reported in adults.

Pathology and staging

Wilms tumor is a soft, pale gray tumor resembling brain tissue. It contains blastema and epithelial and connective tissue components. It is thought to arise from nephrogenic rests in the kidney.

Mutation or deletion of both copies (alleles) of the chromosome 11p WT-1 tumor suppressor gene results in tumorigenesis. The familial disease exhibits autosomal dominant inheritance but is recessive at the cellular level. Affected family members harbor a germ-line WT-1 mutation, conferring susceptibility. One further hit is required, while two hits are required to cause the sporadic disease. This explains why hereditary Wilms tumors tend to develop multifocally and at a slightly younger age than sporadic counterparts.

Tumor staging relates to the relationship of the tumor to the renal capsule, excision margins, and local lymph nodes at nephrectomy, as well as the presence of soft tissue (typically lung) or bone metastases. Histology determines treatment approaches and relates to final outcome:

•Favorable histology in 95% of cases

•Unfavorable (5%) cases: nuclear enlargement (>3-fold), hyperchromasia, abnormal mitoses

•Anaplasia is an unfavorable marker of chemoresistance.

Presentation

Ninety percent of patients have a mass; 33% complain of abdominal or flank pain; 30–50% develop hematuria; 50% are hypertensive; and 15% exhibit other anomalies such as hemihypertrophy, aniridia, and cryptorchidism. It can be a component of Denys–Drash, WAGR (Wilms tumor, Aniridia, Genital anomalies, mental Retardation), Beckwith–Wiedemann, and other uncommon syndromes.

Investigations

The first-line investigation for a child with an abdominal mass or hematuria is ultrasound, which will reveal a renal tumor. Further diagnostic imaging and staging are obtained by CT, including the chest, to evaluate for metastasis.

Percutaneous biopsy is not recommended.

Treatment and prognosis

Children with renal tumors should be managed by a specialist pediatric oncology center. Staging nephrectomy, with or without preoperative or postoperative chemotherapy, remains the mainstay of treatment. NWTSG (National Wilms Tumor Study Group) recommends surgical diagnosis and staging, followed by adjuvant treatment.

WILMS TUMOR AND NEUROBLASTOMA 329

In European countries SIOP (International Society of Pediatric Oncology) treatment involves preoperative chemotherapy followed by surgery.

The chemotherapy most frequently used is actinomycin D, vincristine, and doxorubicin.

Survival is generally good, at >90% overall, ranging from 55% to 97% according to stage and histology. The unfavorable histology is present in a small percentage but accounts for >50% of deaths. Radiation therapy is used selectively for advance disease or for anaplasia.

Neuroblastoma

This is the most common extracranial solid tumor of childhood, with 80% diagnosed in children <4 years old. The tumor is of neural crest origin; 50% occur in the adrenal gland and most of the remaining cases arise along the sympathetic trunks.

Chromosome 1p deletion is found in 25–35% of tumors. An allelic loss of 11p occurs in up to 45%. Familiar forms are rare (<1%) but 20% of these are autosomal dominant.

Presentation

Systemic symptoms and signs are common: fever, abdominal pain/distension, mass, weight loss, anemia, and bone pain. Retro-orbital metastases may cause proptosis.

Imaging and staging

Use ultrasound initially; CT of chest and abdomen. Calcification in tumor helps distinguish neuroblastoma from Wilms tumor. MIBG scans are very sensitive for detection of neuroblastomas.

• Stage 1 Tumor confined to organ of origin and grossly complete excision

• Stage 2 Unilateral tumor with residual disease post-resection or lymphadenopathy

•Stage 3 Tumor crossing midline or contralateral nodes

•Stage 4 Metastatic disease beyond regional nodes; survival 6%

•Stage 4S Unilateral tumor with metastasis limited to liver, skin, or

bone marrow; survival 77%

Treatment and prognosis

Treatment involves surgical excision; radiotherapy; and combination chemotherapy, possibly with autologous bone marrow transplantation. Stage 4S tumors may resolve with little or no treatment.

Prognosis is poor except for stage 1 and 4S disease.

This page intentionally left blank