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Pediatric Renal Masses: Comprehensive Imaging Guide

Overview of Pediatric Renal/Retroperitoneal Masses

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PART I: WILMS TUMOR (NEPHROBLASTOMA)

Epidemiology & Clinical Features

• Most common solid renal tumor of childhood, ~5% of all childhood cancers
• ~650 new cases/year in the USA; peak age is 3rd year of life
• Equal sex distribution, equal kidney frequency; bilateral in 5% of cases
• Most present as an asymptomatic abdominal mass noticed by a parent; sometimes found on a well-child visit
• ~10-15% have metastatic disease at diagnosis; lungs (85-95%) and liver (10-15%) are most common sites

Pathophysiology

• Arises from metanephric blastema - pluripotent embryonal renal precursor cells
• Two-hit hypothesis (Knudson-Strong, 1972): sporadic form = 2 post-zygotic somatic mutations; familial form = 1 germline + 1 somatic mutation
• WT1 gene on chromosome 11p13 is implicated (though only 5-10% of sporadic tumors have WT1 mutations)
• Other genes: IGF1, H19, p57 (Beckwith-Wiedemann), WT2 on 11p15
• Nephrogenic rests (NRs): precursor lesions classified as:
  • Perilobar NRs - located at the periphery of the renal lobe; associated with Beckwith-Wiedemann syndrome
  • Intralobar NRs - within the renal lobe; associated with WAGR, Denys-Drash syndrome

Pathology (Histology)

• Classic triphasic composition: blastema + epithelial + stromal elements in varying proportions
• Favorable histology (FH): all tumors without anaplasia (~90%)
• Unfavorable histology (UH): anaplastic tumors (focal or diffuse), CCSK, rhabdoid tumors
  • Anaplasia in 5%; more common in older children and African-Americans; linked to p53 mutations
  • Diffuse anaplasia = worse prognosis than focal
• Grossly: large, multilobulated, gray-tan with hemorrhage and necrosis; fibrous pseudocapsule often present

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Imaging of Wilms Tumor

Plain Radiography (X-ray / KUB)

• Large soft-tissue flank mass displacing bowel medially and contralaterally
• Calcifications uncommon - present in only ~10% (rim/curvilinear pattern; much less than neuroblastoma)
• Bowel gas pattern shows displacement; rarely a mass effect on the ipsilateral psoas shadow
• Chest X-ray: look for pulmonary metastases ("cannon ball" lesions)

Ultrasound (First-line modality)

• Intrarenal origin confirmed - normal renal tissue seen displaced/compressed around the mass ("claw sign")
• Large, heterogeneous, echogenic or mixed echogenicity mass
• Assessment of renal vein and IVC tumor thrombus (Doppler critical)
• Can identify bilateral tumors and contralateral kidney
• Cystic components, hemorrhage, or necrosis seen as hypoechoic areas
• Nephrogenic rests appear as peripheral hypoechoic rim lesions

CT (Computed Tomography) - Primary staging modality

• Pre-contrast: heterogeneous, well-circumscribed intrarenal mass, usually hypodense to normal renal parenchyma
• Post-contrast (nephrographic phase): heterogeneous enhancement; the "claw sign" of normal enhancing renal parenchyma curving around the tumor margin is characteristic
• Confirms renal origin of mass
• Evaluates: bilateral tumors, lymph nodes, IVC/renal vein thrombus, liver metastases
• Calcifications in ~10% (peripheral/scattered, unlike neuroblastoma's coarse stippled calcification)
• Tumor does NOT cross midline (unlike neuroblastoma which encases/displaces great vessels across midline)
• Aorta displaced posteriorly by the mass (contrast with neuroblastoma which displaces aorta anteriorly)
• Pulmonary metastases: CT chest detects small lesions not seen on CXR; COG vs SIOP differ on chest CT significance
• "Rule of 10's": ~10% unfavorable histology, 10% bilateral, 10% vascular invasion, 10% calcifications, 10% lung metastases at presentation

MRI - Preferred for bilateral tumors and vascular assessment

• T1W: low signal intensity mass with variable heterogeneity
• T2W: variable to high signal intensity; high signal nephrogenic rests (if cystic) or hypointense sclerotic NRs
• "Claw sign" of normal renal tissue well shown on T2W
• DWI (Diffusion-weighted imaging): restricted diffusion in non-cystic Wilms components; ADC substantially higher than neuroblastoma - useful differentiator
• Gadolinium-enhanced MRI: heterogeneous enhancement pattern
• Superior to CT for: bilateral tumors, nephroblastomatosis, IVC extension, no ionizing radiation
• MRA (MR angiography): useful for surgical resectability planning

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Wilms Tumor Staging (COG/NWTS System)

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Associated Syndromes with Wilms Tumor

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PART II: NEUROBLASTOMA

Epidemiology & Clinical Features

• Most common extracranial solid tumor of childhood; ~8-10% of all pediatric cancers
• Median age at diagnosis: 18 months; 90% diagnosed before age 5
• Arises from neural crest cells of the adrenal medulla (most common site, ~35%) or anywhere along the sympathetic chain (paravertebral, paraspinal, mediastinum, neck, pelvis)
• Often presents as an ill child with abdominal distension, weight loss, fever, hypertension, bone pain, "raccoon eyes" (periorbital ecchymosis from orbital metastases), "blueberry muffin" skin nodules (neonatal)
• Elevated urinary catecholamine metabolites (VMA, HVA) in >90% of cases - key diagnostic marker

Pathophysiology

• Differentiates along sympathoadrenal lineage
• Spectrum: neuroblastoma (undifferentiated) → ganglioneuroblastoma (intermediate) → ganglioneuroma (benign, well-differentiated)
• Key prognostic molecular markers: MYCN amplification (poor prognosis), ALK mutation, chromosomal abnormalities (1p deletion, 11q deletion, 17q gain)
• Segmental chromosomal abnormalities vs numerical chromosomal abnormalities (better prognosis)

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Imaging of Neuroblastoma

Plain Radiography

• Calcifications visible in 50-60% on plain film (stippled, granular, "popcorn" pattern) - much more common than Wilms
• Soft-tissue mass; may show rib erosion or vertebral body involvement
• Chest X-ray may show paraspinal widening (posterior mediastinal mass) or pleural effusion

Ultrasound

• Suprarenal heterogeneous mass with coarse echogenic foci (calcifications)
• Displaces the kidney inferiorly and laterally (vs Wilms which is intrarenal)
• Doppler: assesses vascular encasement; the aorta may be elevated/lifted
• Liver: assess for metastatic involvement (diffuse infiltration or focal hypoechoic masses)

CT - Key imaging modality

• Large retroperitoneal suprarenal mass, often crossing the midline
• Calcifications in 80-90% on CT (coarse, stippled, amorphous)
• Aorta encased/displaced ANTERIORLY - classic distinguishing feature from Wilms (which pushes aorta posteriorly)
• Heterogeneous enhancement with necrotic areas
• Engulfs and encases great vessels (aorta, IVC, celiac axis, SMA) without occluding them - "vascular encasement sign"
• Lymphadenopathy: retroperitoneal, paraaortic nodes
• Intraspinal extension via neural foramina ("dumbbell tumor") in 10% abdominal, 28% thoracic
• Liver metastases: focal hypoenhancing masses or diffuse infiltration
• Bone cortex involvement, marrow infiltration

MRI - Preferred for staging and intraspinal extension

• T1W: low to intermediate signal
• T2W: high signal intensity; excellent contrast between tumor and surrounding tissues; preferred for intraspinal dumbbell extension
• DWI: restricted diffusion with low ADC values (substantially lower than Wilms - key differentiator)
• MIBG scintigraphy (meta-iodobenzylguanidine): functional imaging - highest specificity (85%) for staging bone/marrow disease; positive in ~90% of tumors
• Combined MRI + MIBG: sensitivity 99%, specificity 95%
• MRI preferred over CT for: intraspinal extension, liver metastases (T2W hyperintense), bone marrow infiltration, radiation avoidance
• ¹²³I-MIBG scan: whole-body staging for bone, bone marrow, soft tissue disease

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Neuroblastoma Staging (INRG / INSS)

INSS (International Neuroblastoma Staging System) - post-surgical

INRG (International Neuroblastoma Risk Group) - pre-surgical, image-defined

• Vascular encasement (aorta, IVC, renal vessels, celiac axis, SMA)
• Intraspinal extension (> 1/3 spinal canal)
• Involvement of adjacent organs (liver, diaphragm, kidney)
• Infiltration of structures at neck/thoracic inlet

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Associated Syndromes with Neuroblastoma

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PART III: HEAD-TO-HEAD COMPARISON - WILMS vs NEUROBLASTOMA

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PART IV: OTHER PEDIATRIC RENAL MASSES

1. Congenital Mesoblastic Nephroma (CMN)

• Most common renal tumor in neonates (< 3 months); mean age at presentation 3.5 months
• Benign spindle-cell tumor; two subtypes: classic (fibrous) and cellular (more aggressive)
• Imaging: large, solid, intrarenal mass replacing most of the kidney; hypoechoic on US; heterogeneous on CT/MRI; no calcifications; no pseudocapsule
• Treated with nephrectomy alone (classic type); cellular type may recur - close follow-up

2. Clear Cell Sarcoma of Kidney (CCSK)

• "Bone-metastasizing renal tumor of childhood" - propensity for bone metastases (unlike Wilms)
• Peak age 1-4 years; males predominate
• Pathology: monomorphous spindle/ovoid cells with arborizing vasculature; mucoid extracellular matrix
• Imaging: large, homogeneous, intrarenal mass; CT shows hypodense well-circumscribed mass; may have cysts and calcifications; MRI preferred - intermediate T1, heterogeneous T2
• No specific imaging features to distinguish from Wilms preoperatively
• Treatment includes doxorubicin (unlike favorable-histology Wilms Stage I-II)

3. Rhabdoid Tumor of Kidney (RTK)

• Most aggressive renal tumor of childhood; very young infants (< 2 years, peak 11 months)
• Associated with brain tumors (primitive neuroectodermal tumors/AT/RT) - SMARCB1/INI1 mutation
• Pathology: large vesicular cells with prominent nucleoli and cytoplasmic inclusions
• Imaging: infiltrative large intrarenal mass; subcapsular fluid collection is characteristic; calcifications (~25%); often metastatic at diagnosis (bone, brain, lungs)
• CT: heterogeneous mass; subcapsular crescent may be seen
• Brain MRI mandatory to exclude synchronous primitive neuroectodermal tumor of brain

4. Multilocular Cystic Nephroma (MLCN)

• Benign cystic renal tumor; bimodal age distribution (boys < 2 years; women 30-50 years)
• Imaging: well-circumscribed multi-septated cystic mass; septa may herniate into renal pelvis (CT/MRI "herniation sign" into collecting system)
• CT: multiple non-communicating cysts separated by enhancing septa
• Shares features with multicystic dysplastic kidney (MCDK) and cystic Wilms; cystic Wilms occurs in children ~2-4 years

5. Renal Cell Carcinoma (RCC) in Children

• Rare in children (<5% of pediatric renal tumors); more common in adolescents
• Often associated with: Xp11.2 translocation (TFE3 gene), VHL disease, tuberous sclerosis, hereditary papillary RCC
• Imaging: similar to adult RCC - heterogeneous solid renal mass, CT shows arterial phase enhancement; calcifications more common than in adults with childhood RCC
• Xp11.2 translocation RCC: calcifications, lymph node metastases, may have papillary architecture

6. Renal Lymphoma

• Rare primary; secondary involvement more common in NHL
• Bilateral diffuse infiltration or multiple hypoechoic/hypodense masses
• CT: "multiple soft tissue masses" pattern; minimal enhancement

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PART V: IMAGING MODALITY SUMMARY FOR PEDIATRIC RENAL MASSES

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Quick Reference: Key Distinguishing Imaging Clues

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