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PE20.7 | Wilms Tumor — SDL Guide

Learning Objectives

• Describe the clinical presentation of Wilms tumor and identify the key examination trap (do not palpate vigorously)
• Explain the pathophysiology, genetics (WT1), and histology of nephroblastoma including the significance of anaplasia
• Recognise the associated syndromes (WAGR, Beckwith-Wiedemann, Denys-Drash) that increase Wilms tumor risk
• Apply the NWTS staging system (I–V) to determine management: nephrectomy + chemotherapy ± radiation ± nephron-sparing for bilateral disease
• Differentiate Wilms tumor from neuroblastoma on clinical, laboratory, and imaging grounds

INSTRUCTIONS

Wilms tumor — also called nephroblastoma — is the most common primary renal malignancy of childhood and one of the great success stories of paediatric oncology: with multimodal treatment, over 90% of children with localised disease are cured. Yet three traps persist in clinical practice: missing the abdominal mass because it is painless and the child appears well; vigorous abdominal palpation that ruptures the tumour and upstages the disease; and confusing Wilms with neuroblastoma, the two most important causes of abdominal mass in young children. This module gives you the knowledge to avoid all three.

References

• Ghai Essential Pediatrics, 9th ed., Ch. 19 — Paediatric Oncology (textbook)
• Nelson Textbook of Pediatrics, 21st ed., Ch. 522 — Wilms Tumor (textbook)
• Children's Oncology Group (COG) AREN protocols; SIOP Renal Tumour Study Group guidelines (guideline)

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Version 2.0 | NMC CBUC 2024

Clinical Presentation of Wilms Tumor

Wilms tumor (nephroblastoma) is the most common primary renal tumour in children, accounting for approximately 6% of all childhood cancers. It peaks between 3 and 4 years of age, though it can occur from infancy to adolescence. The cardinal and most important presenting feature is an asymptomatic abdominal mass discovered incidentally — most commonly by a parent during bathing, dressing, or play, or by a nurse or physician during a routine physical examination. The fact that the child appears completely well despite a large intraabdominal tumour is a defining and deceptive characteristic: parents often delay seeking attention because the child seems healthy.

The clinical features of Wilms tumor span renal, vascular, and constitutional domains, and can be organised as follows:

• Abdominal mass: large, smooth, firm, and well-defined; confined to one side (unilateral in ~94% of cases); does NOT cross the midline (contrast with neuroblastoma); non-tender; moves with respiration
• Haematuria: microscopic (~25%) or macroscopic (~12%); may be the presenting symptom without a palpable mass
• Hypertension: in ~25% of cases, due to renin secretion by the tumour or compression of the renal artery; may cause headache
• Abdominal pain: uncommon; if acute pain occurs, consider spontaneous intratumoral haemorrhage or rupture
• Fever and weight loss: suggest advanced or bilateral disease
• Constitutional symptoms (malaise, anorexia) are unusual and indicate extensive disease

CRITICAL EXAMINATION RULE: Do NOT vigorously palpate the abdomen of a child in whom Wilms tumor is suspected. Vigorous palpation risks tumour capsule rupture, which releases malignant cells into the peritoneum, converts the tumour from Stage I/II to Stage III, and significantly increases the intensity (and toxicity) of required treatment. Examination should be gentle and limited to confirming the presence and side of the mass.

Wilms Tumour: Unilateral Abdominal Mass and Triphasic Histology

Pathophysiology, Genetics, and Associated Syndromes

Wilms tumor is a mixed embryonal tumour that arises from persistent metanephric blastema — the embryonic precursor cells of the kidney — that fail to differentiate normally during nephrogenesis. This explains both its occurrence in young children and its characteristic histological composition.

Histology — triphasic pattern:
The classic Wilms tumour is composed of three elements in varying proportions, reflecting the three lineages of normal kidney development. This triphasic pattern is diagnostically characteristic and distinguishes nephroblastoma from other paediatric renal masses — a purely monophasic or biphasic tumour should prompt consideration of clear cell sarcoma or rhabdoid tumour, which have different treatment protocols. The three distinct components, described here in order of their prognostic and biological significance in Wilms tumor research and treatment stratification, are:
• Blastemal component: small, round, primitive blue cells — the undifferentiated metanephric blastema; drives tumour growth and chemosensitivity
• Stromal component: spindle cells, smooth muscle, adipose tissue — mesenchymal derivatives
• Epithelial component: forming primitive tubules and glomeruli — partially differentiated towards renal epithelium

Anaplasia (nuclear enlargement ≥3× normal + hyperchromatic multipolar mitoses) is the key adverse histological feature and is found in ~5–10% of cases. Diffuse anaplasia carries a significantly worse prognosis and requires more intensive therapy. Focal anaplasia is intermediate-risk. Absence of anaplasia = favourable histology with excellent cure rates.

WT1 Genetics and Triphasic Wilms Tumour Histology

Genetics:
WT1 (Wilms Tumor gene 1) on chromosome 11p13 is the key tumour suppressor gene. Loss of both alleles (two-hit model) disrupts normal metanephric differentiation and drives tumorigenesis. However, WT1 is mutated in only ~10–15% of sporadic Wilms tumours; other loci (WT2 at 11p15, WTX, CTNNB1) are involved in the majority. The sporadic form is the most common (~95%); familial Wilms is rare.

Associated syndromes:

Syndrome	Features	Wilms Risk
WAGR syndrome	Wilms + Aniridia + Genito-urinary anomalies + intellectual Retardation; WT1 deletion at 11p13	~50%
Beckwith-Wiedemann syndrome (BWS)	Macroglossia, hemihypertrophy, omphalocele, hyperinsulinaemia (neonatal hypoglycaemia); WT2 locus (IGF2 upregulation)	~5–10%
Denys-Drash syndrome	Diffuse mesangial sclerosis (nephrotic syndrome) + pseudohermaphroditism + Wilms; WT1 point mutation	>90%

Children with these syndromes require surveillance ultrasonography every 3 months until age 7–8 years. Bilateral Wilms tumor (Stage V, ~6% of cases) is more common in syndromic patients.

Diagnosis, Investigation, and Staging

Diagnosis of Wilms tumor proceeds through a structured sequence of imaging and staging investigations. Importantly, in most centres following COG (American) protocols, nephrectomy is performed upfront without pre-operative biopsy, with pathological staging confirmed at surgery; in centres following SIOP (European) protocols, pre-operative chemotherapy is given to shrink the tumour before surgery. Understanding both approaches is required for examinations.

Provided image

Imaging workup:
Imaging in Wilms tumor serves two sequential purposes: first, to characterise the primary renal mass and confirm its intrarenal origin; second, to stage the disease by identifying local extension, lymph node involvement, vascular invasion, and distant metastases. Ultrasound is always the first modality, with CT providing definitive staging. The key imaging findings that support Wilms over neuroblastoma on ultrasound are: intrarenal origin, smooth well-defined borders, and absence of calcification.
• Abdominal ultrasound (first-line imaging): confirms a solid intrarenal mass, assesses the contralateral kidney (bilateral disease?), tumour vascularity (Doppler), renal vein or IVC extension (tumour thrombus is present in ~4% of cases)
• Contrast-enhanced CT of chest and abdomen: defines the extent of local disease (capsular breach, lymph node involvement, adjacent organ invasion), detects pulmonary metastases (the most common site of haematogenous spread)
• Chest X-ray: pulmonary metastases present as round nodules; mandatory initial staging
• Bone scan and brain imaging only if clinically indicated (bone mets rare)

NWTS Staging (National Wilms Tumor Study / Children's Oncology Group):

Stage	Definition
I	Tumour confined to kidney and completely resected; no capsule breach; no vascular involvement
II	Extends beyond renal capsule but completely resected (local spread but negative margins)
III	Residual non-haematogenous tumour in abdomen (peritoneal spill/biopsy, positive lymph nodes, incomplete resection)
IV	Haematogenous metastases (lung, liver, bone, brain)
V	Bilateral Wilms tumor

Differentiating Wilms tumor from neuroblastoma — the two most important abdominal masses in young children:

Key distinguishing features at a glance:
• Wilms: smooth mass stays within one flank, does NOT cross midline; no calcification (rare); urinary catecholamines NORMAL; arises from kidney (intrinsic); better prognosis
• Neuroblastoma: irregular, may cross midline, CALCIFICATION on plain X-ray (~85%), urinary VMA/HVA (homovanillic + vanillylmandelic acid) ELEVATED; arises from adrenal or sympathetic chain; worse prognosis in advanced disease