Overview
Definition:
Wilms tumor, also known as nephroblastoma, is a pediatric malignancy of the kidney, representing the most common primary renal tumor in children
It typically arises from metanephric blastema, an embryonic tissue
Associations with congenital anomalies, such as aniridia, are clinically significant, influencing management strategies.
Epidemiology:
Wilms tumor accounts for approximately 6-8% of all childhood cancers and 90% of pediatric renal tumors
The incidence is about 1 in 10,000 live births globally, with a bimodal age distribution peaking between 2-5 years
Bilateral tumors occur in 5-10% of cases
There is a higher incidence in certain populations and in children with specific genetic syndromes.
Clinical Significance:
Early diagnosis and timely, appropriate management of Wilms tumor are crucial for improving survival rates and minimizing long-term sequelae
Understanding the association with aniridia is important for genetic counseling, risk stratification, and management planning, particularly regarding bilateral disease and nephron-sparing approaches.
Clinical Presentation
Symptoms:
Abdominal mass, often palpable and smooth
Abdominal pain, which may be diffuse or localized
Hematuria, gross or microscopic, is present in about 15-20% of cases
Hypertension, due to renin secretion by the tumor, occurs in a significant minority
Fever, lethargy, and weight loss are non-specific systemic symptoms
Aniridia may be noted at birth or during examination.
Signs:
A palpable abdominal mass, typically firm and non-tender, found in the flank or abdomen
Abdominal distension
Evidence of hypertension (elevated blood pressure)
Signs of anemia (pallor)
Rarely, a palpable supraclavicular lymph node or evidence of metastatic disease (e.g., bone pain).
Diagnostic Criteria:
Diagnosis is primarily based on imaging and histopathological confirmation
Clinical suspicion arises from presenting symptoms and signs
Imaging (ultrasound, CT, MRI) reveals a renal mass
Definitive diagnosis is made through biopsy and examination of tumor tissue, identifying characteristic nephroblastomatous histology
Staging is based on the extent of local disease and presence of metastasis.
Diagnostic Approach
History Taking:
Detailed history of abdominal swelling, pain, or hematuria
Inquiry about associated congenital anomalies, particularly aniridia
Family history of cancer or Wilms tumor
Assess for constitutional symptoms like fever or weight loss
History of any prior abdominal surgery or trauma.
Physical Examination:
Thorough abdominal examination to palpate and characterize any mass, noting its size, location, mobility, and consistency
Assess for tenderness
Check for abdominal distension
Measure blood pressure to screen for hypertension
Examine for any signs of metastatic disease, including lymphadenopathy or bone tenderness
A careful ocular examination is essential to confirm or rule out aniridia.
Investigations:
Abdominal ultrasound is usually the initial imaging modality, demonstrating a renal mass
Contrast-enhanced CT scan of the abdomen and pelvis is essential for evaluating tumor extent, involvement of renal vessels and ureter, and lymph node status
Chest X-ray or CT scan of the chest is mandatory for staging to detect lung metastases
Complete blood count (CBC) to assess for anemia or thrombocytosis
Renal function tests (urea, creatinine)
Urinalysis to check for hematuria
Tumor markers are generally not useful for diagnosis but may be used in specific contexts
Molecular genetic testing may be considered for patients with bilateral tumors or specific genetic syndromes.
Differential Diagnosis:
Other pediatric renal tumors (e.g., clear cell sarcoma of the kidney, rhabdoid tumor of the kidney)
Neuroblastoma, especially if the mass is adrenal or extends beyond the kidney
Lymphoma involving the kidney
Mesoblastic nephroma (in neonates)
Hydronephrosis
Renal abscess
Angiomyolipoma
Multicystic dysplastic kidney.
Management
Initial Management:
The management of Wilms tumor is multimodal, involving surgery, chemotherapy, and sometimes radiotherapy
The goal is to achieve a complete cure while preserving renal function and minimizing long-term toxicity
Initial management involves accurate staging and risk stratification based on histology and clinical stage
For patients with aniridia, especially with suspected bilateral involvement, a multidisciplinary approach is paramount.
Surgical Management:
Radical nephrectomy is the standard treatment for unilateral, localized Wilms tumor without extensive contralateral involvement
For bilateral Wilms tumors, or tumors in a solitary kidney, nephron-sparing surgery (partial nephrectomy) is preferred to preserve renal function
The timing of nephrectomy is critical
it is generally performed after neoadjuvant chemotherapy for advanced stages or bilateral disease
In localized unilateral disease, immediate nephrectomy is often performed
For patients with aniridia and bilateral tumors, biopsy and possible debulking of the contralateral tumor may be done initially, followed by systemic chemotherapy and delayed surgical management of both kidneys.
Chemotherapy:
Chemotherapy is integral to the treatment of Wilms tumor
The choice of agents and duration depends on the stage and histology
Common agents include vincristine, dactinomycin, and doxorubicin (VINDICIN regimen)
For high-risk histology or advanced stage disease, additional agents like etoposide or cyclophosphamide may be used
Neoadjuvant chemotherapy is often given before surgery for bilateral tumors or stage III/IV disease to reduce tumor bulk and facilitate surgery
Postoperative chemotherapy is guided by the final histopathological findings and response to treatment
Specific protocols (e.g., National Wilms Tumor Study protocols) guide treatment decisions.
Radiotherapy:
Radiotherapy is typically reserved for patients with higher stage disease (stage III or IV), unfavorable histology, or residual tumor after surgery
It is generally not used for localized, favorable histology unilateral Wilms tumors treated with adequate surgery and chemotherapy
Its use requires careful consideration due to potential long-term side effects in children, including secondary malignancies and growth disturbances.
Aniridia Specific Considerations
Association With Wilms Tumor:
Aniridia is part of the WAGR syndrome (Wilms tumor, Aniridia, Genitourinary anomalies, intellectual disability), often associated with a deletion on chromosome 11p13
Patients with aniridia have a significantly increased risk of developing Wilms tumor
Bilateral Wilms tumors are more common in children with aniridia and WAGR syndrome.
Screening And Surveillance:
Children with aniridia should undergo regular abdominal ultrasound screening for Wilms tumor from birth, typically every 3-4 months until at least age 7 years
This intensive screening aims to detect tumors at an early, surgically curable stage, allowing for nephron-sparing surgery when feasible.
Timing Of Nephrectomy In Aniridia:
In children with aniridia and bilateral Wilms tumors, the timing of surgery is crucial
Often, initial management involves biopsy of suspicious contralateral lesions and chemotherapy, with delayed bilateral partial nephrectomies to preserve maximal renal function
Decisions are individualized based on tumor characteristics, extent, and response to chemotherapy.
Complications
Early Complications:
Hemorrhage from the tumor or surgical site
Wound infection
Renal vein or vena cava thrombosis
Adynamic ileus
Acute kidney injury.
Late Complications:
Chronic kidney disease due to loss of renal mass, particularly after nephrectomy for bilateral disease
Hypertension
Secondary malignancies, especially after radiotherapy
Growth and developmental delays
Infertility
Cardiotoxicity from anthracyclines
Gastrointestinal issues
Hearing impairment from certain chemotherapeutic agents.
Prevention Strategies:
Meticulous surgical technique to minimize blood loss and preserve healthy renal parenchyma
Judicious use of chemotherapy and radiotherapy, adhering to risk-stratified protocols
Close monitoring for side effects of treatment
Genetic counseling and counseling regarding long-term health surveillance.
Prognosis
Factors Affecting Prognosis:
Stage of the tumor at diagnosis is the most critical prognostic factor
Histologic type (favorable vs
unfavorable)
Presence of bilateral disease
Response to initial therapy
Patient age and overall health status
Presence of aniridia and WAGR syndrome can be associated with bilateral disease and requires specialized management.
Outcomes:
With current multimodal therapy, the overall survival rate for Wilms tumor is over 90%
Favorable histology, early-stage disease, and unilateral tumors have excellent prognoses
Unfavorable histology (e.g., anaplastic, rhabdoid) and distant metastases are associated with a poorer prognosis, but significant advances have been made
For bilateral Wilms tumors, particularly in the context of aniridia, nephron-sparing surgery and aggressive chemotherapy can achieve good long-term renal function and survival.
Follow Up:
Long-term follow-up is essential for detecting tumor recurrence and managing late treatment-related toxicities
This includes regular physical examinations, blood pressure monitoring, renal function tests, and imaging (e.g., ultrasound, CT) as indicated
Screening for secondary malignancies and monitoring for growth and developmental milestones are also critical components of survivorship care.
Key Points
Exam Focus:
Wilms tumor is the most common pediatric renal malignancy
Aniridia is a key associated anomaly, often part of WAGR syndrome, increasing risk of bilateral Wilms tumor
Regular screening with abdominal ultrasound is vital for children with aniridia
Nephron-sparing surgery is preferred for bilateral disease or solitary kidneys
Chemotherapy regimens (VINDICIN) are standard
Unfavorable histology and advanced stage impact prognosis.
Clinical Pearls:
Always consider Wilms tumor in a child with an abdominal mass
Palpate the abdomen carefully and measure blood pressure
Inquire about associated congenital anomalies, especially aniridia
If bilateral Wilms tumor is suspected, especially in a child with aniridia, avoid biopsy without immediate surgical and oncological consultation
neoadjuvant chemotherapy is often the first step
Preserve as much renal tissue as possible.
Common Mistakes:
Delaying diagnosis due to assuming the mass is benign
Performing an unnecessary biopsy without proper oncological planning, potentially leading to tumor seeding
Inadequate surgical resection, leaving residual tumor
Over-reliance on single imaging modality without cross-sectional imaging for staging
Not considering bilateral disease in patients with aniridia or family history.