Wilms Tumor

Wilms tumor is an intrarenal tumor of neoplastic embryonal renal cells of the metanephros. Wilms tumor is the most common malignant renal tumor of childhood. It accounts for about 6% of all childhood cancers. There are about 450 to 500 cases of Wilms tumor diagnosed in the United States annually, for an incidence of 8 cases per million in children under 15 years of age. It occurs with equal frequency in males and females, and there is a slightly higher incidence of disease in African American children than in Caucasian and Asian children. The median age at diagnosis of Wilms tumor is about 3 years of age, with earlier diagnosis occurring in bilateral tumors. The incidence of bilateral tumors is 7%.

Common Symptoms:

1. Abdominal or flank mass, may be unilateral or bilateral, generally smooth and firm

2. Abdominal pain, found in nearly half of patients, due to hemorrhage into the tumor

3. Hematuria, often microscopic

4. Hypertension, found in up to 25% of patients at presentation. Possible etiologies include: renin production by the tumor, renal ischemia secondary to pressure on the renal artery, or intraparenchymal AV fistula formation.

Associated Anomalies:

Wilms tumor is associated with a number of congenital anomalies and syndromes:

1. WAGR syndrome — Wilms tumor, Aniridia, Genital anomalies, and mental Retardation. This syndrome is associated with a constitutional deletion on chromosome 11 (del 11p13 — the WT1 locus), and the incidence of Wilms tumor in this syndrome is over 40%.

2. Beckwith-Weideman syndrome — an overgrowth syndrome characterized by excess growth at the cellular, tissue and organ levels. It is associated with organomegaly, macroglossia, hypoglycemia, omphalocele and hemihypertrophy. Beckwith-Weideman syndrome is caused by a change in the gene locus at band p15.5 on chromosome 11 — the WT2 locus. The risk of Wilms tumor with Beckwith-Weideman syndrome is from 10 to 20%.

3. Denys-Drash syndrome — a very rare syndrome of male pseudohermaphroditism (or genitourinary abnormalities), renal mesangial sclerosis and Wilms tumor. The genetic abnormality in these infants also maps to chromosome 11, p13, but it is a dominant negative, missense mutation.

4. Aniridia — children with sporadic aniridia are at risk for Wilms tumor. The incidence of aniridia in patients with Wilms tumor is 1.1%

5. Children with horseshoe kidney are at twice the risk of developing Wilms tumor when compared to the general population.

Diagnosis:

When an abdominal mass is discovered, the initial imaging modality of choice is ultrasound. Imaging is essential prior to treatment to accurately localize the source of the mass, identify any genitourinary abnormalities that may co-exist, and to examine the contralateral kidney. Ultrasound can indicate if the mass is intrarenal (suggestive of Wilms tumor) or extrarenal, suggesting another cause, such as a neuroblastoma. A CT is often the next imaging modality of choice, which can confirm the location and extent of the tumor, assess the vena cava, and evaluate the contralateral kidney. A chest radiograph is also performed in order to rule out pulmonary metastases, as up to 15% of patients will have pulmonary metastases at the time of diagnosis.

Differential Diagnosis Abdominal/Pelvic Tumors

Neuroblastoma: will usually have increased urinary metanephrines (VMA, HVA)

NHL: Increased LDH, bone marrow infiltration

Rhabdomyosarcoma: present in a wider range of ages, can affect the urogenital system and may present with vaginal bleeding or paratesticular mass

Germ Cell Tumor: increased serum beta hcg and/or AFP

Hepatoblastoma/Hepatoma: increased serum AFP

Other Renal Tumors: mesoblastic nephroma (neonates), clear cell sarcoma, rhabdoid tumor, renal cell carcinoma

Staging:

The Children’s Oncology Group (COG) has designed a staging system for Wilms tumor that incorporates clinical, surgical, and pathological information. Tumors with favorable histology do not have anaplasia. Unfavorable histology is defined as any presence of anaplasia.

Stage 1 — these tumors are limited to the kidney, are encapsulated and can be removed complete and intact.

Stage 2 — the tumor extends beyond the kidney, but is completely resected with negative margins. May have regional extension of the tumor.

Stage 3 – Residual tumor post-op is confined to the abdomen — the tumor is NOT completely resectable.

Stage 4 — Hematogenous mets are present, often in the lung.

Stage 5 — Bilateral renal involvement is present at diagnosis.

Treatment:

The COG recommendation for treatment for unilateral tumors is immediate surgical removal of the affected kidney via flank incision. In the European countries, the International Society of Pediatric Oncology (SIOP) recommends pre-operative chemotherapy to reduce the size of the primary tumor to aid in surgical removal. Outcomes are similar with either approach. Both groups agree that after complete physical and radiographic evaluation of the tumor, surgical resection is necessary. Most Wilms tumors are too large to consider a partial nephrectomy, so a complete nephrectomy is standard. For localized disease, combination chemotherapy with vincristine and actinomycin is given after surgery. For advanced stage disease, radiation is required in addition to surgery and chemotherapy.

Prognosis:

Currently, around 80 to 90% of patients with Wilms tumor can be cured with conventional treatment modalities. However, patients with advanced stage disease (metastases, recurrence, loss of heterozygosity of 1p and 16q) and/or unfavorable histology have a poor prognosis.

References:

1. Coppes, M. Principles of WilmsTumor Biology. Urologic Clinics of North America. 2000; 27(3):423-433.

2. Neville, H. Wilms Tumor. Urologic Clinics of North America. 2000; 27(3). 435-442.

3. Behrman. Neoplasms of the Kidney: Wilms Tumor. Nelson Textbook of Pediatrics, 19^th Ed. W.B. Saunders. 2011.

4. Cotrain. Robbins Pathologic Basis of Disease. W.B. Saunders. 1999;487-489.

5. Wilm's Tumor . Pediatrics in Review April 2008