What are the diagnostic steps for Wilms tumor?

Diagnosis of Wilms Tumor

Wilms tumor diagnosis requires imaging with ultrasound or CT scan to identify the renal mass, followed by surgical resection with histopathological confirmation, while genetic testing should be performed to identify predisposition syndromes that guide surveillance and family counseling. 1, 2, 3

Initial Clinical Presentation and Imaging

Presenting Features

• Most children present with an asymptomatic abdominal mass, though some may have flank pain, hematuria, fever, or a palpable lump 4, 5
• The tumor is the most common primary malignant renal tumor of childhood, accounting for approximately 7% of all childhood cancers with about 500 new cases annually in the United States 5, 6

Primary Imaging Studies

• Abdominal ultrasound is typically the initial imaging modality for detection of a renal mass 1, 6
• CT scan of chest, abdomen, and pelvis with contrast is essential for complete staging and surgical planning 2, 6
• Imaging must identify critical features including tumor size, laterality (unilateral vs. bilateral), vascular involvement, lymph node involvement, and distant metastases 6, 3

Important caveat: Bilateral tumors (present in approximately 5-7% of cases) often indicate genetic predisposition syndromes and require different management approaches with 4-year event-free survival of approximately 43.8% 1

Histopathological Confirmation

Tissue Diagnosis

• Definitive diagnosis requires histopathological examination of surgical specimens, as imaging alone cannot reliably distinguish Wilms tumor from other pediatric renal tumors 2, 4, 3
• Biopsy is generally not recommended prior to surgical resection in typical presentations, as surgery provides both diagnosis and treatment 2, 3
• The tumor can be separated into two main histology types: favorable histology (>90% of cases) and anaplastic histology, which dramatically affects prognosis and treatment 2, 3

Histological Features

• Wilms tumor is an embryonal tumor developing from remnants of immature kidney tissue 5
• Classic triphasic pattern includes blastemal, stromal, and epithelial components 2, 5
• Anaplastic features (nuclear enlargement, hyperchromasia, and abnormal mitotic figures) must be identified as they confer worse prognosis 3

Genetic Testing - Critical Component

Genetic testing for predisposition syndromes should be considered as part of comprehensive evaluation in all patients with Wilms tumor. 1

Key Genetic Syndromes to Test

• WT1 pathogenic variants: Associated with Denys-Drash syndrome and WAGR syndrome; these patients require abdominal ultrasound every 3 months from birth through age 7 years 7, 1
• TRIM28 variants: Found in 86% of epithelial-predominant histology tumors; patients with this histology should be specifically tested 1
• REST, CTR9, and DIS3L2: Additional predisposition genes that require tailored surveillance 1
• DICER1 syndrome: Carriers require biannual abdominal ultrasound until age 8, then annually thereafter 7, 1

Clinical Importance of Genetic Testing

• Identifies patients requiring intensified surveillance protocols 1
• Enables genetic counseling and family screening, as bilateral tumors often represent genetic predisposition requiring surveillance of family members 1
• Informs prognosis and may influence treatment intensity 1, 3

Staging Evaluation

Complete Staging Workup

• Chest CT is mandatory to evaluate for pulmonary metastases, the most common site of distant spread 2, 6, 3
• Abdominal/pelvic CT or MRI to assess local tumor extent, lymph node involvement, and contralateral kidney 6, 3
• Assessment for inferior vena cava thrombus, which can occur but is not a contraindication to surgery 4

Controversy alert: There is ongoing debate regarding the significance of pulmonary nodules <5 mm detected at initial staging, as these may represent benign findings but can affect stage assignment 6

Laboratory Studies

• Complete blood count, comprehensive metabolic panel including renal function 2
• Urinalysis (hematuria may be present) 4
• No specific tumor markers are diagnostic for Wilms tumor 2, 5

Management by Multidisciplinary Team

• All patients must be managed by a multidisciplinary team with experience in pediatric renal tumors; consulting a pediatric oncologist is strongly encouraged 2, 3
• Treatment planning depends on stage, histology (favorable vs. anaplastic), and genetic factors 1, 3
• Five-year survival exceeds 90% for children with favorable histology who receive appropriate treatment, but is much lower for higher-stage diffuse anaplastic disease 2, 5, 3

Key Diagnostic Pitfalls to Avoid

• Do not perform needle biopsy in typical presentations, as this can cause tumor spillage and upstage the disease 2, 3
• Do not miss bilateral disease, which fundamentally changes management and indicates genetic predisposition 1, 3
• Do not skip genetic testing, as this affects both the patient's surveillance and family counseling 1
• In adults, Wilms tumor often masquerades as renal cell carcinoma and requires high index of suspicion 4