Definition/General
Introduction:
Wilms tumor is the most common primary kidney tumor in children
Represents 6% of all childhood cancers
Shows triphasic histology with blastemal, epithelial, and stromal components
Embryonal kidney tumor.
Origin:
Arises from nephrogenic rests (persistent metanephric blastema)
Results from abnormal kidney development
Associated with WT1 gene mutations
Can be sporadic or syndromic.
Classification:
WHO classification: Nephroblastoma (Wilms tumor)
Favorable histology (no anaplasia)
Anaplastic (focal or diffuse)
Blastemal-predominant after chemotherapy
COG staging system.
Epidemiology:
Peak incidence 2-5 years
Equal gender distribution
Bilateral in 5-10%
Associated with WAGR, BWS, Denys-Drash syndromes
95% diagnosed by age 10.
Clinical Features
Presentation:
Abdominal mass (90%)
Painless swelling
Abdominal distension
Hypertension (25%)
Hematuria (20%)
Fever (20%)
Anemia.
Symptoms:
Asymptomatic abdominal mass
Hypertension (renin-mediated)
Gross hematuria
Abdominal pain
Vomiting
Constipation
Weight loss.
Risk Factors:
Beckwith-Wiedemann syndrome
WAGR syndrome
Denys-Drash syndrome
Hemihypertrophy
Genitourinary anomalies
Family history (rare).
Screening:
Abdominal ultrasound
CT/MRI imaging
Genetic counseling (syndromic cases)
Screening protocols for high-risk syndromes
Urinalysis.
Master Wilms Tumor Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Large, well-circumscribed mass
Variegated cut surface
Gray-pink, soft areas
Cystic spaces
Hemorrhage and necrosis
Pseudocapsule.
Characteristics:
Soft, fleshy consistency
Lobulated surface
Heterogeneous appearance
Cysts and solid areas
Focal calcification
Well-demarcated from kidney.
Size Location:
Large tumors (average 10-15 cm)
Unilateral (90%)
Bilateral synchronous (5%)
Bilateral metachronous (1-2%)
Replaces kidney
May extend into renal vein.
Multifocality:
Bilateral tumors in 10%
Multifocal within same kidney
Associated nephrogenic rests
Higher in syndromic cases
Synchronous more common than metachronous.
Microscopic Description
Histological Features:
Classic triphasic pattern: Blastemal, epithelial, and stromal components
Blastemal: Small blue cells
Epithelial: Tubules, glomeruloid structures
Stromal: Mesenchymal differentiation.
Cellular Characteristics:
Blastemal cells: Small, round, hyperchromatic nuclei
Epithelial cells: Larger, forming tubules
Stromal cells: Spindle-shaped, fibrous
Variable differentiation
Mitotic activity high.
Architectural Patterns:
Blastemal sheets
Epithelial tubules and glomeruli
Stromal spindle cells
Heterologous elements (muscle, cartilage, bone)
Cystic areas
Anaplastic foci (if present).
Grading Criteria:
Favorable histology: No anaplasia
Anaplastic: Nuclear enlargement (3x), hyperchromasia, atypical mitoses
Focal anaplasia: <10% of tumor
Diffuse anaplasia: >10% or extrarenal.
Immunohistochemistry
Positive Markers:
WT1 - positive (nuclear, blastemal/epithelial)
PAX8 - positive
Six2 - positive (blastemal)
Vimentin - positive (stromal)
Cytokeratin - positive (epithelial)
EMA - positive (epithelial).
Negative Markers:
CD99 - negative (vs Ewing)
Desmin - negative (except heterologous muscle)
MyoD1 - negative
S-100 - negative
CD45 - negative.
Diagnostic Utility:
WT1 highly sensitive and specific
PAX8 supports renal origin
Six2 highlights blastemal component
Helps distinguish from other small round cell tumors
Loss of WT1 in some anaplastic areas.
Molecular Subtypes:
WT1-positive: Classic Wilms tumor
WT1-negative: May represent other entities
Blastemal-predominant: Six2+, high proliferation
Anaplastic: Variable WT1, p53+.
Molecular/Genetic
Genetic Mutations:
WT1 mutations (15-20%)
WTX mutations (15-30%)
CTNNB1 mutations (15%)
TP53 mutations (anaplastic)
MYCN amplification (poor prognosis)
Chromosome 16q loss.
Molecular Markers:
WT1 gene inactivation
Wnt pathway activation
p53 pathway (anaplastic)
IGF2 overexpression
microRNA dysregulation
DNA hypermethylation.
Prognostic Significance:
Histology: Favorable vs anaplastic
Stage: Most important factor
Age: >2 years better
Anaplasia: Focal better than diffuse
MYCN amplification: Poor prognosis
LOH 1p/16q: Intermediate risk.
Therapeutic Targets:
Multi-agent chemotherapy
Actinomycin D, vincristine, doxorubicin
Radiation therapy (stage III/IV)
IGF pathway inhibitors
WNT pathway modulators
Immunotherapy trials.
Differential Diagnosis
Similar Entities:
Clear cell sarcoma of kidney
Rhabdoid tumor
Congenital mesoblastic nephroma
Multicystic cystic nephroma
Renal cell carcinoma
Lymphoma.
Distinguishing Features:
Wilms tumor: WT1+, triphasic, favorable age
Clear cell sarcoma: Monomorphic, vascular
Rhabdoid tumor: INI1 loss, aggressive
Mesoblastic nephroma: Neonatal, spindle cells
RCC: Older children, different IHC.
Diagnostic Challenges:
Monophasic Wilms tumor
Cystic partially differentiated nephroblastoma
Blastemal-predominant after therapy
Anaplastic vs high-grade other tumors
Nephrogenic rests.
Rare Variants:
Teratoid Wilms tumor
Wilms tumor with extensive necrosis
Cystic partially differentiated nephroblastoma
Epithelial-predominant Wilms tumor.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Nephrectomy specimen with tumor measuring [X] cm
Microscopic Features
Classic triphasic Wilms tumor with blastemal, epithelial, and stromal components. [Anaplasia present/absent]
Anaplasia Assessment
Anaplasia: [Absent/Focal/Diffuse]
Stage
Stage [I/II/III/IV/V] based on [staging criteria]
Margins
Surgical margins: [negative/positive]
Nephrogenic Rests
Nephrogenic rests: [present/absent]
Immunohistochemistry
WT1: Positive, PAX8: Positive, Six2: Positive (blastemal)
Final Diagnosis
Wilms tumor (nephroblastoma), [favorable/anaplastic] histology, Stage [X]