WILMS TUMOR

WILMS TUMOR - Timothy L.Black, MD
BASICS
DESCRIPTION
• An embryonal renal neoplasm containing blastema, stromal, or epithelial cell types, usually affecting children before age 5 years.
• For staging, see "Prognosis" section.
• System(s) Affected: Renal/Urologic
• Synonym(s): Nephroblastoma
ALERT
Pediatric Considerations
• Occurs only in children
• Most common renal malignancy in childhood
EPIDEMIOLOGY
• Predominant age: Median age of 36.5 months
• Predominant sex: Female > Male (1.1:1)
Incidence
• Frequency rarer in East Asian populations than whites (1)[C]
• Frequency higher in black children than whites (1)[C]
Prevalence
US: 0.69/100,000. 7.6 cases/1 million children under 15 years of age
RISK FACTORS
• Aniridia (partial or complete absence of iris) 600 times greater than normal risk
• Hemihypertrophy (100 times greater than normal risk)
• Cryptorchidism
• Hypospadias
• Duplicated renal collecting systems
• Wiedemann-Beckwith syndrome
• Denys-Drash syndrome (nephropathy, renal failure, male pseudohermaphroditism, Wilms tumor)
• Klippel-Trenaunay syndrome
• WAGR complex (Wilms tumor, aniridia, genitourinary malformations, and mental retardation)
• Beckwith-Wiedemann syndrome (visceromegaly, macroglossia, omphalocele, hyperinsulinemic hypoclycemia)
• Familial occurrence (1-2%)
• Paternal occupation (see "Etiology")
Genetics
• Several congenital anomalies are known to be associated with Wilms tumor. A 2-stage mutational model has been proposed: Occurrence in either hereditary form or sporadic form. Patients with aniridia have a deletion of the short arm of chromosome 11 (11p13).
• Abnormalities of chromosome 11 at the 11p15 locus are associated with Beckwith-Wiedemann syndrome
• Wilms tumor suppressor gene (WT1) has been identified as well as additional candidates for another suppressor gene (WT2) (1)[C]
• Chromosome band 17q12-21 has been linked to two kindreds with Wilms tumor and other kindreds are associated with a Wilms tumor predisposition gene at 19q13.3-q13.4 (1)[C]
ETIOLOGY
• Hereditary or sporadic forms of genetic mutation
• Familial form: autosomal dominant trait with incomplete penetrance (1%)
• Potential of paternal occupational exposure (machinists, welders, motor vehicle mechanics, auto body repairmen)
ASSOCIATED CONDITIONS
See "Risk Factors."


DIAGNOSIS
SIGNS AND SYMPTOMS
• Usually asymptomatic
• Palpable upper abdominal mass
• Abdominal pain
• Fever
• Anemia
• Rarely, signs of acute abdomen with free intraperitoneal rupture
• Cardiac murmur
• Hepatosplenomegaly
• Ascites
• Prominent abdominal wall veins
• Varicocele
• Gonadal metastases
• Aniridia
History
History of increasing abdominal size
Physical Exam
Palpable abdominal mass
TESTS
Lab
• Urinalysis (occasional hematuria)
• CBC (anemia)
• Lactate dehydrogenase
• Plasma renin (rarely helpful)
• Urine catecholamines
Imaging
• Chest x-ray
• Kidney, ureter, bladder (presence of linear calcifications)
• Abdominal ultrasound: Gives best information about tumor extension into inferior vena cava
• CT (with IV and oral contrast) of chest and abdomen
• IV pyelogram rarely helpful
Diagnostic Procedures/Surgery
Occasionally, bone marrow aspiration necessary to distinguish from neuroblastoma
Pathological Findings
• Favorable findings (mortality of 7%)
- Bulky lesion, well encapsulated
- Focal areas of hemorrhage and necrosis
- Absence of anaplasia and sarcomatous cell types
- Presence of blastema, stomal, and epithelial elements
• Unfavorable histology (mortality rate of 57%)
- Anaplasia: Markedly enlarged and multipolar mitotic figures, 3-fold enlargement of nuclei in comparison with adjacent similar nuclei, hyperchromasia of enlarge nuclei. Anaplasia may be diffuse or focal.
- Sarcomatous changes: Now considered to be separate from Wilms, not subtypes (mortality 64%)
• Nephroblastomatosis: Considered premalignant
DIFFERENTIAL DIAGNOSIS
• Neuroblastoma
• Hepatic tumor
• Sarcoma
• Rhabdoid tumor
• Cystic nephroma
• Mesoblastic nephroma
• Renal cell carcinoma (generally occurs in older children)
TREATMENT
GENERAL MEASURES
• Appropriate health care: Inpatient workup and treatment until stable postoperative and induction chemotherapy completed
• Chemotherapy
• Radiation therapy in Stage II, unfavorable histology, Stage II and Stage IV
Diet
No special diet
Activity
As tolerated
MEDICATION (DRUGS)
First Line
• Dactinomycin (actinomycin-D)
• Vincristine
• Doxorubicin
• Cyclophosphamide (Cytoxan)
• Ifosphamide
• Etoposide
• Contraindications: Refer to the manufacturer's literature for each drug.
• Precautions: Refer to the manufacturer's literature for each drug.
• Significant possible interactions: Refer to the manufacturer's literature for each drug.
Second Line
• Doxorubicin (Adriamycin)
• Cyclophosphamide
SURGERY
• Examination (visual and manual) of contralateral kidney
• Radical nephroureterectomy and biopsies as needed to provide precise staging information
• Sampling of any enlarged lymph nodes
• Identification of any retained tumor with titanium clips
• Tumor should be given to pathologist fresh, not in formalin.
• Vertical midline incision if tumor extension to right atrium present (possible use of cardiopulmonary bypass)
• With bilateral Wilms tumors, biopsy, then chemotherapy and 2nd-look operation 6 weeks to 6 months later for partial bilateral nephrectomy if possible
- Preopoerative treatment also generally accepted in a solitary kidney, horseshoe kidneys, intravascular extension of tumor above the intrahepatic vena cava, and in the case of respiratory distress from extensive metastatic tumor
FOLLOW-UP
DISPOSITION
Issues for Referral
Surgical complications have been found to be significantly higher if the radical nephrectomy is done by a general surgeon rather than an pediatric surgeon or a pediatric urologist. (2)[B]
PROGNOSIS
• With favorable histology, 91% survival
• With diffuse anaplasia, 20% survival
• With focal anaplasia, 64% survival
• With rhabdoid features, 19% 3-year survival
• Staging
- I: Tumor limited to kidney, completely excised
- II: Tumor extends beyond kidney, completely excised
- III: Residual nonhematogenous tumor confined to abdomen (lymph nodes positive, spillage of tumor, peritoneal implants, extension beyond resection region)
- IV: Hematogenous metastases
- V: Bilateral renal involvement
COMPLICATIONS
• 1-2% will develop second malignant neoplasms (leukemia, lymphoma, hepatocellular carcinoma, soft tissue sarcoma)
• High risk of low-birth-weight infants, perinatal mortality in offspring of female survivors of Wilms tumor
• Chest is usual site of recurrence.
• Occurrence of second malignant neoplasms in 2% of patients 7-34 years after treatment
• Surgical complications: (2)[B]
- Postoperative hemorrhage
- Postoperative small bowel obstruction (5-7%)
- Tumor rupture with spillage in 19%. This may be spontaneous or surgical and results in upstaging the tumor. Only 2.7% of spills are considered avoidable. (3)[B]
• Local tumor recurrence
PATIENT MONITORING
• Multidrug chemotherapy every 3-4 weeks for 16 weeks: 15 months depending on stage
• Every 4 months for 1 year, every 6 months for 2nd to 3rd year, yearly after that
• Complete blood count, CT of chest and abdomen with each visit
REFERENCES
1. Ashcraft KW, Holcomb GW, Murphy JP, eds. Pediatric Surgery, 4th ed. Philadelphia, PA: Elsevier Saunders; 2005.
2. Ritchey ML, et al. Surgical complications after primary nephrectomy for Wilms tumor: Report from the national Wilms tumor study group. J Am Coll Surg. 2001;192:63-68.
3. Ehrlich PF, et al. Quality assessment for Wilms tumor: A report from the national Wilms study-5. J Ped Surg. 2005;40:208-210.
MISCELLANEOUS
Other notes
• Mesoblastic nephroma: Distinguished only by histology. Age usually 6 months. Essentially benign, although metastases have been reported; tends to be locally invasive. Operative spillage may lead to recurrence. No chemotherapy or radiotherapy needed with complete excision.
• Nephroblastomatosis: Considered premalignant; may present as nodularity of one or both kidneys; treated with biopsy and local excision (renal tissue sparing)