Pediatrics (System-Integrated)

Wilms tumor: presentation and workup

Clinical Overview and When to Suspect Wilms Tumor

— Peak incidence 2–5 years (median ~3.5 years); rare after age 10.

— Embryonal tumor arising from metanephric blastema; histology classically shows triphasic pattern (blastemal, epithelial, stromal).

— ~5–10% are bilateral or multifocal, often presenting earlier and in syndromic patients.

— A previously well toddler whose parent feels an asymptomatic abdominal mass while bathing or dressing the child.

— Incidental painless flank/abdominal fullness on routine well-child exam.

— Child with a known predisposition syndrome presenting with new hypertension, hematuria, or palpable mass.

— WAGR syndrome (WT1 deletion, 11p13): Wilms, Aniridia, GU anomalies, Range of developmental delay.

— Denys-Drash: WT1 mutation → diffuse mesangial sclerosis (early nephrotic syndrome), pseudohermaphroditism, Wilms.

— Beckwith-Wiedemann (11p15, WT2 region): macroglossia, omphalocele, hemihypertrophy, hyperinsulinemic hypoglycemia.

— Isolated hemihypertrophy and sporadic aniridia also confer risk.

— Slight female predominance; higher incidence in Black children, lower in East Asian populations.

— ~90% overall survival with modern multimodal therapy — outcomes are excellent if recognized and staged appropriately.

Board pearl: A smooth, firm, painless flank mass that does not cross the midline in a 2–4-year-old = Wilms until proven otherwise; a mass that crosses midline with calcifications and systemic illness points to neuroblastoma instead. This single distinction is one of the most repeated pediatric oncology vignettes on USMLE exams and should be your reflex pivot before ordering imaging.

Wilms tumor (nephroblastoma) is the most common primary renal malignancy of childhood and the most common abdominal solid tumor in children under 5.

When to suspect on Step 3 / pediatric boards:

Key genetic and syndromic associations (test these cold):

Epidemiology pearls:

Presentation Patterns and Key History

— Children typically do not look sick — a critical contrast with neuroblastoma, where the child is often irritable, febrile, and weight-losing.

— Abdominal pain or distention (~30–40%), often dull.

— Gross or microscopic hematuria (~25%) from tumor invasion of the collecting system.

— Hypertension (~25%) from renin secretion or renal artery compression.

— Fever, anorexia, malaise in larger or ruptured tumors.

— Acute abdomen if tumor hemorrhage or rupture after minor trauma.

— Hemoptysis or respiratory symptoms → pulmonary metastases (lungs are the #1 metastatic site).

— Varicocele (especially left-sided, non-reducing) → tumor thrombus in renal vein/IVC.

— Lower extremity edema, hepatomegaly, ascites → IVC obstruction.

— Age at presentation and rate of mass growth.

— Personal/family history of GU anomalies (hypospadias, cryptorchidism), aniridia, hemihypertrophy, macroglossia, omphalocele.

— Prior screening ultrasounds (children with predisposition syndromes receive abdominal US every 3 months until age 7–8).

— Recent abdominal trauma (raises concern for tumor rupture, upstages disease).

— Bleeding diathesis screen — ~8% have acquired von Willebrand disease.

Key distinction: Wilms tumor presents in a well-appearing child with a painless flank mass; neuroblastoma presents in a systemically ill child with periorbital ecchymoses, opsoclonus-myoclonus, or bone pain. The history of "mass found while bathing my otherwise healthy toddler" is essentially pathognomonic for Wilms on board exams and should drive your initial workup pathway.

Classic presentation: an asymptomatic, healthy-appearing toddler with a mass discovered incidentally by a caregiver during routine activities (bathing, diaper change) or by the pediatrician at a well-child visit.

Symptoms that may accompany the mass (present in a minority):

Red-flag features suggesting advanced disease:

Targeted history to obtain on the Step 3 vignette:

Physical Exam Findings and Hemodynamic Assessment

— Smooth, firm, non-tender flank mass, usually unilateral.

— Does not typically cross the midline (kidney-bound); a mass that crosses midline favors neuroblastoma or hepatoblastoma.

— Avoid deep or repeated palpation — risk of tumor rupture and intraperitoneal seeding, which upstages disease and worsens prognosis. Document the mass once and place a sign at the bedside: "Do not palpate abdomen."

— Mass moves with respiration (retroperitoneal origin).

— Measure blood pressure in all four extremities or at minimum confirm with appropriate-sized cuff; hypertension is present in ~25%.

— Tachycardia or hypotension after trauma → suspect intratumoral or intraperitoneal hemorrhage.

— Look for signs of IVC obstruction: lower extremity edema, dilated abdominal wall veins, hepatomegaly.

— Aniridia (slit-lamp or penlight): suggests WAGR.

— Hemihypertrophy/hemihyperplasia: compare limb lengths and facial symmetry.

— Macroglossia, omphalocele/umbilical hernia, ear creases/pits: Beckwith-Wiedemann.

— Genitourinary anomalies: cryptorchidism, hypospadias, ambiguous genitalia (Denys-Drash, WAGR).

— Left-sided varicocele that does not decompress when supine → renal vein/IVC tumor thrombus.

Step 3 management: On suspecting Wilms, stop deep abdominal palpation, place "no palpation" precautions, obtain BP, and proceed directly to abdominal ultrasound. Premature biopsy or aggressive exam can rupture the tumor capsule and convert local disease into stage III, mandating whole-abdomen radiation. Recognizing this hands-off principle is a frequent board distractor.

General appearance: well-nourished, well-developed child — not toxic or cachectic. This single observation reorients many vignettes away from neuroblastoma or leukemia/lymphoma.

Abdominal exam — the cornerstone:

Vital signs and hemodynamics:

Targeted exam for syndromic features:

Pulmonary exam: auscultate for decreased breath sounds or effusion (metastatic disease).

Diagnostic Workup — Initial Labs and Imaging

— Confirms a solid intrarenal mass distinct from adrenal origin (favors Wilms over neuroblastoma).

— Doppler evaluates renal vein and IVC for tumor thrombus — present in ~4–10% and changes surgical approach.

— Assesses contralateral kidney for synchronous bilateral disease (~5–10%).

— Defines tumor extent, lymph node involvement, contralateral kidney, liver metastases.

— MRI preferred in some centers to minimize radiation, especially for predisposition syndrome surveillance and bilateral disease.

— Lungs are the #1 metastatic site; pulmonary nodules upstage to stage IV.

— Plain chest X-ray alone is insufficient — CT detects sub-radiographic nodules that alter therapy.

— CBC (anemia from hemorrhage; baseline before chemo).

— CMP including creatinine, electrolytes, liver enzymes, calcium, LDH, uric acid.

— Urinalysis — hematuria common; proteinuria suggests Denys-Drash–associated nephropathy.

— Coagulation panel + von Willebrand panel — acquired vWD in ~8%, must identify before surgery/biopsy.

— Urine catecholamines (HVA, VMA) — to exclude neuroblastoma; elevated in 90% of neuroblastomas, normal in Wilms.

— AFP, β-hCG if hepatoblastoma or germ cell tumor in differential.

Board pearl: Always order urine HVA/VMA early — a vignette describing a child with a flank mass plus elevated catecholamines is neuroblastoma, not Wilms, and the entire management pathway diverges (MIBG scan, bone marrow biopsy, N-myc amplification). Conversely, normal catecholamines + intrarenal mass on US + well child = proceed down the Wilms staging pathway, which begins with CT chest/abdomen and surgical consultation rather than biopsy.

First-line imaging: abdominal ultrasound with Doppler.

Cross-sectional imaging: contrast-enhanced CT abdomen/pelvis (or MRI).

Staging chest imaging: CT chest (mandatory).

Initial laboratory studies:

Tumor markers to consider in atypical presentations:

Diagnostic Workup — Advanced and Confirmatory Studies

— In North America (COG protocols): upfront radical nephroureterectomy with lymph node sampling is standard for unilateral, resectable disease — surgery both confirms diagnosis and provides staging.

— In Europe (SIOP protocols): preoperative chemotherapy is given first, then nephrectomy — shrinks tumor and reduces intraoperative rupture risk. Step 3 follows COG/US practice.

— Percutaneous needle biopsy is generally avoided in resectable tumors — violates the capsule and upstages to stage III.

— Bilateral disease (preserve renal parenchyma).

— Tumor in a solitary kidney.

— IVC thrombus extending above the hepatic veins.

— Unresectable tumor at presentation, or extension into adjacent organs.

— Pulmonary or extensive metastatic disease where upfront chemo improves resectability.

— Favorable histology (FH): classic triphasic blastemal/epithelial/stromal pattern, ~90% of cases.

— Unfavorable histology (UH): diffuse anaplasia (large hyperchromatic nuclei, atypical mitoses) — much worse prognosis, more intensive therapy.

— Molecular markers: loss of heterozygosity at 1p and 16q, 1q gain → higher-risk stratification and intensified chemotherapy in modern COG protocols.

Key distinction: COG = surgery first, then chemo; SIOP = chemo first, then surgery. US boards expect the COG pathway, but knowing the rationale for preoperative chemo (bilateral, solitary kidney, unresectable, extensive thrombus) is repeatedly tested as the exception that proves the rule.

Definitive diagnosis is surgical-pathologic, not radiographic.

Indications for preoperative biopsy or neoadjuvant chemo (US practice):

Pathology — features that drive risk stratification:

Echocardiogram before anthracycline (doxorubicin) chemotherapy — baseline LV function.

Audiology baseline if carboplatin planned.

Genetic counseling and germline testing if syndromic features, bilateral disease, or age <2 — identifies WT1, WT2, TP53 (anaplastic), REST, CTR9 mutations and informs sibling/future-child screening.

Risk Stratification and First-Line Management Logic

— Stage I: tumor confined to kidney, completely resected, capsule intact.

— Stage II: tumor extends beyond kidney but completely resected (e.g., into perirenal fat or renal sinus vessels).

— Stage III: residual non-hematogenous tumor confined to abdomen — positive margins, positive nodes, preoperative or intraoperative spill/rupture, biopsy prior to resection, or peritoneal implants.

— Stage IV: hematogenous metastases (lung, liver, bone, brain) or lymph nodes outside abdomen/pelvis.

— Stage V: bilateral renal involvement at diagnosis.

— Very low risk: stage I FH, age <2, tumor <550 g → may be observed after surgery alone on protocol.

— Low/standard risk: stage I–II FH.

— Higher risk: stage III–IV FH, or any anaplastic (UH) disease, or LOH 1p/16q.

— Surgery (radical nephroureterectomy + lymph node sampling) for all unilateral resectable disease.

— Adjuvant chemotherapy for nearly all patients (regimen depends on stage/histology).

— Radiation therapy for stage III+ disease and for unfavorable histology.

Step 3 management: When the vignette asks "next step after diagnosis of a unilateral, resectable Wilms tumor," the answer is radical nephroureterectomy with regional lymph node sampling, not biopsy and not neoadjuvant chemotherapy. Reserve preoperative chemo for bilateral disease, solitary kidney, IVC thrombus above hepatic veins, or unresectable tumor — memorize this short list as it drives nearly every management-branch question on the topic.

Staging (Children's Oncology Group, postsurgical):

Risk groups combine stage + histology + molecular markers:

General management framework:

Why lymph node sampling matters: failure to sample nodes automatically upstages the patient to stage III on COG criteria — a common test question and a real surgical quality metric.

Avoid intraoperative spill — converts stage I/II to stage III and mandates abdominal radiation.

Pharmacotherapy — First-Line Chemotherapy Regimens

— Vincristine (V) — neurotoxicity (peripheral neuropathy, constipation, jaw pain, SIADH); vesicant.

— Dactinomycin (actinomycin D, A) — hepatotoxicity, especially veno-occlusive disease (sinusoidal obstruction syndrome).

— Doxorubicin (D) — cumulative cardiotoxicity; requires baseline and surveillance echocardiograms.

— Stage I/II favorable histology: regimen EE-4A = vincristine + dactinomycin × ~18 weeks, no radiation.

— Stage III/IV favorable histology: regimen DD-4A = vincristine + dactinomycin + doxorubicin + abdominal/flank radiation (and whole-lung RT if pulmonary mets persist after initial chemo).

— Diffuse anaplasia or higher-risk biology: regimen M or UH-1/UH-2 — adds cyclophosphamide, etoposide, carboplatin; intensified radiation.

— LOH 1p/16q or 1q gain: intensified regimen even if stage I–II.

— Antiemetics (ondansetron ± dexamethasone).

— Tumor lysis prophylaxis in bulky disease — hydration, allopurinol or rasburicase if high uric acid.

— G-CSF as needed for neutropenia in higher-intensity regimens.

— Echocardiogram before each doxorubicin cycle threshold and at long-term follow-up.

— LFTs before each dactinomycin dose; hold for transaminitis or VOD signs (RUQ pain, hepatomegaly, weight gain, thrombocytopenia).

— Indicated for stage III+ disease, unfavorable histology, and persistent pulmonary metastases.

— Whole-abdomen RT for diffuse peritoneal spill; flank RT for localized stage III.

Board pearl: Dactinomycin + radiation = veno-occlusive disease risk (hepatomegaly, ascites, hyperbilirubinemia, thrombocytopenia, weight gain). Doxorubicin = late cardiomyopathy — lifelong echo surveillance. Vincristine = neurotoxicity and SIADH. Matching the toxicity to the drug is a perennial Step 3 oncology pearl, and Wilms is the classic vehicle for testing it in pediatric vignettes.

Backbone agents used across nearly all Wilms regimens:

Regimen selection by risk group (COG framework):

Supportive care and monitoring during chemotherapy:

Radiation therapy:

Surgical and Procedural Management

— Transabdominal (transperitoneal) approach preferred — allows full abdominal exploration, contralateral kidney inspection, and adequate node sampling.

— Avoid flank/retroperitoneal approach — limits exposure and node sampling.

— Avoid preoperative biopsy in resectable tumors — upstages to stage III.

— En bloc resection with intact capsule is the goal; intraoperative spill upstages to stage III and mandates abdominal radiation.

— Sample regional hilar, para-aortic, and paracaval nodes.

— Absent node sampling = automatic stage III per COG rules — a quality metric and a board-favorite test point.

— Thrombus below hepatic veins: often resectable at primary surgery.

— Thrombus above hepatic veins or into right atrium: preoperative chemotherapy to shrink thrombus; may require cardiopulmonary bypass for resection.

— Bilateral biopsy + neoadjuvant chemotherapy first, then nephron-sparing surgery (partial nephrectomy) on both sides if feasible — preserves long-term renal function and avoids dialysis/transplant.

— Persistent pulmonary nodules after induction chemo may be resected and/or irradiated.

— Type and cross — tumors are vascular; hemorrhage risk.

— Treat acquired von Willebrand disease preoperatively (DDAVP or vWF concentrate) if identified.

— Stress-dose considerations if prior steroids.

CCS pearl: In the CCS-style vignette, the order set for newly diagnosed unilateral Wilms is: NPO, IV fluids, type and crossmatch, CBC/CMP/coags/vWF panel, urine catecholamines, abdominal US with Doppler, CT chest/abdomen/pelvis, echocardiogram, pediatric surgical oncology consult, pediatric hematology-oncology consult, and avoid abdominal palpation. Biopsy is not part of the standard order set.

Radical nephroureterectomy with regional lymph node sampling is the cornerstone procedure for unilateral resectable Wilms.

Lymph node sampling is mandatory:

IVC and atrial tumor thrombus management:

Bilateral (stage V) disease:

Metastasectomy:

Vascular access: central venous access (port or tunneled line) placed at or near time of nephrectomy for chemotherapy delivery.

Perioperative considerations:

Special Populations — Renal and Hepatic Considerations

— Nephron-sparing surgery (partial nephrectomy) preferred when oncologically feasible to avoid dialysis.

— Preoperative chemotherapy to shrink tumor and maximize residual parenchyma.

— Long-term GFR monitoring is essential; survivors of unilateral nephrectomy have ~30% risk of hyperfiltration injury, proteinuria, and hypertension over decades.

— WT1 mutation causes diffuse mesangial sclerosis → early nephrotic syndrome and progressive renal failure, often before tumor diagnosis.

— These children frequently need bilateral prophylactic nephrectomy and renal replacement therapy even in the absence of bilateral tumors.

— Dactinomycin and radiation predispose to hepatic veno-occlusive disease (sinusoidal obstruction syndrome) — presents with painful hepatomegaly, weight gain/ascites, hyperbilirubinemia, and thrombocytopenia.

— Hold dactinomycin for elevated transaminases or bilirubin; consider defibrotide for severe VOD.

— Reduce dactinomycin dose in significant hepatic dysfunction.

— Adjust acyclovir, fluconazole, vancomycin, and aminoglycosides per residual GFR.

— Avoid nephrotoxins (NSAIDs, IV contrast when possible, aminoglycosides) in solitary-kidney survivors.

— Annual blood pressure, urinalysis for proteinuria, and serum creatinine.

— ACE inhibitor or ARB if proteinuria or hypertension develops, to reduce hyperfiltration injury.

— Counsel against contact sports involving the remaining kidney is no longer routinely advised — current AAP guidance individualizes the decision; most children with a solitary kidney can participate with appropriate protective equipment and shared decision-making.

Key distinction: Denys-Drash = early renal failure dominates the picture and may require bilateral nephrectomy regardless of tumor laterality, whereas WAGR or sporadic Wilms usually has preserved baseline renal function and standard unilateral nephrectomy suffices. Recognizing the syndrome dictates the surgical plan.

Solitary kidney or pre-existing renal dysfunction:

Denys-Drash syndrome:

Hepatic considerations and chemotherapy:

Renal-dosing of supportive medications:

Long-term renal surveillance after unilateral nephrectomy:

Special Populations — Syndromic, Infant, and Adolescent Presentations

— Beckwith-Wiedemann, isolated hemihypertrophy, WAGR, Denys-Drash, Perlman, Simpson-Golabi-Behmel, Frasier, Bloom, Li-Fraumeni: all warrant screening abdominal ultrasound every 3 months until age 7–8 years (some protocols to age 4 for low-risk subgroups based on molecular subtype in BWS).

— Surveillance detects smaller, earlier-stage, more curable tumors.

— Watch for neonatal hyperinsulinemic hypoglycemia — check glucose at birth and during illness.

— Macroglossia may cause airway issues.

— AFP screening every 3 months for hepatoblastoma until age 4 — a co-occurring embryonal tumor in the same syndrome.

— Most likely diagnosis is congenital mesoblastic nephroma, not Wilms — usually benign, treated by nephrectomy alone, no chemotherapy.

— Wilms is uncommon under 6 months; classic age window is 2–5 years.

— Wilms is rare after age 10; differential shifts toward renal cell carcinoma, clear cell sarcoma of the kidney, rhabdoid tumor.

— Clear cell sarcoma = "bone-metastasizing tumor of childhood."

— Rhabdoid tumor = highly aggressive, associated with synchronous CNS atypical teratoid/rhabdoid tumors; INI1/SMARCB1 loss.

Board pearl: <6 months + renal mass = mesoblastic nephroma; 2–5 years + flank mass = Wilms; >10 years + renal mass = RCC or clear cell sarcoma/rhabdoid tumor. Anchoring the differential to age at presentation is one of the highest-yield pediatric oncology pattern-recognition tasks on the boards.

Predisposition syndromes and surveillance protocols (test these directly):

Beckwith-Wiedemann specifics:

Infants (<6 months) with a renal mass:

Adolescents and young adults:

Pregnancy: not directly relevant — pediatric tumor — but adult Wilms tumor survivors considering pregnancy need preconception counseling regarding cardiotoxicity from prior doxorubicin (echo before pregnancy) and prior abdominal/pelvic radiation (increased risk of preterm birth, low birth weight, placental complications, and infertility).

Complications and Adverse Outcomes

— Intratumoral or intraperitoneal hemorrhage, often after minor trauma — presents as acute abdomen and hemodynamic instability.

— Tumor rupture with intraoperative or preoperative spill — upstages to stage III, mandates whole-abdomen radiation.

— IVC/right atrial tumor thrombus with pulmonary embolism or Budd-Chiari–like syndrome.

— Acquired von Willebrand disease (~8%) — surgical and procedural bleeding risk.

— Hypertensive crisis from renin secretion.

— Tumor lysis syndrome with chemotherapy initiation in bulky disease.

— Vincristine: neuropathy, ileus/constipation, jaw pain, SIADH with hyponatremia.

— Dactinomycin: veno-occlusive disease, mucositis, myelosuppression.

— Doxorubicin: acute arrhythmia, myelosuppression, mucositis; extravasation injury.

— Radiation: enteritis, hepatitis, nephritis of remaining kidney if in field.

— Cardiomyopathy and CHF from anthracyclines — risk increases with dose, younger age at treatment, female sex, and chest radiation.

— Second malignancies — sarcomas, breast cancer, thyroid cancer (especially in radiation fields); leukemia from alkylators/etoposide.

— Chronic kidney disease in solitary-kidney survivors — hyperfiltration, hypertension, proteinuria.

— Pulmonary fibrosis or restrictive lung disease after whole-lung radiation.

— Infertility and gonadal failure after alkylators or pelvic/abdominal radiation.

— Musculoskeletal: scoliosis, soft-tissue hypoplasia in radiation field.

— Endocrinopathies: hypothyroidism if neck in radiation field.

Step 3 management: Every Wilms survivor needs a Children's Oncology Group Long-Term Follow-Up survivorship plan with periodic echo, BP, urinalysis, serum creatinine, breast cancer screening starting at age 25 (if chest RT), and second-malignancy vigilance. The transition from pediatric to adult survivorship clinic is a critical Step 3 care-coordination touchpoint.

Tumor-related acute complications:

Treatment-related acute toxicities:

Late effects (lifelong cancer-survivor surveillance):

Psychosocial and developmental: school absences, learning disabilities (especially with cranial irradiation for CNS mets), anxiety/depression.

When to Escalate Care — ICU, Consult, and Inpatient Triage

— Tumor rupture with hemorrhagic shock — large-bore IV access, crystalloid resuscitation, blood products, emergent surgical consultation.

— Massive IVC or right atrial tumor thrombus with hemodynamic compromise or pulmonary embolism.

— Hypertensive emergency from renin-secreting tumor.

— Tumor lysis syndrome with hyperkalemia, acute kidney injury, or symptomatic hypocalcemia.

— Veno-occlusive disease with rapidly rising bilirubin, ascites, and renal failure during chemotherapy.

— Pediatric hematology-oncology — leads chemotherapy planning and protocol enrollment.

— Pediatric surgical oncology or urology — primary surgical resection.

— Pediatric radiation oncology — for stage III+ or unfavorable histology.

— Pediatric anesthesia — preoperative airway, vascular access, vWD risk.

— Genetics — predisposition syndrome evaluation, germline testing, family counseling.

— Pediatric cardiology — baseline echo before anthracyclines.

— Pediatric nephrology — solitary kidney, bilateral disease, or Denys-Drash.

— Social work and child life — family support, school liaison.

— Febrile neutropenia (ANC <500, temp ≥38.3°C or sustained ≥38.0°C) — broad-spectrum antibiotics (e.g., cefepime) within 60 minutes of presentation.

— Severe mucositis with inability to tolerate oral intake.

— Suspected VOD, typhlitis, or CNS infection.

— Uncontrolled vomiting/dehydration after chemotherapy.

CCS pearl: In a CCS case of newly diagnosed Wilms with fever and ANC 300 on day 10 post-chemotherapy, the first orders are blood cultures × 2 (peripheral + central line), CBC, CMP, lactate, urinalysis/culture, chest X-ray, and empiric IV cefepime — all within the first hour. Delay in antibiotics in febrile neutropenia is a graded patient-safety failure.

Immediate ICU-level concerns:

Mandatory specialty consultations at diagnosis:

Inpatient admission triggers during therapy:

Referral to a Children's Oncology Group–affiliated center is the standard of care — improves protocol enrollment, multidisciplinary access, and survival outcomes.

Key Differentials — Same-Category Renal Masses

— Adrenal or paraspinal origin; crosses the midline and encases vessels rather than displacing them.

— Calcifications common on imaging (~85%).

— Child appears systemically ill — fever, weight loss, bone pain, periorbital ecchymoses ("raccoon eyes"), opsoclonus-myoclonus-ataxia, Horner syndrome.

— Urine HVA/VMA elevated; MIBG scan positive; bone marrow involvement common.

— N-myc amplification drives risk stratification.

— Most common renal tumor in infants <6 months.

— Usually benign; treated by nephrectomy alone.

— Cellular variant (ETV6-NTRK3 fusion) overlaps with infantile fibrosarcoma.

— "Bone-metastasizing renal tumor of childhood."

— Older children, more aggressive than Wilms; metastasizes to bone and brain.

— Treated with more intensive chemotherapy including doxorubicin and cyclophosphamide.

— Highly aggressive; infants and young toddlers.

— SMARCB1 (INI1) loss; associated with synchronous CNS atypical teratoid/rhabdoid tumors.

— Very poor prognosis.

— Older children and adolescents (>10 years).

— Translocation-associated RCC (Xp11.2/TFE3) most common pediatric subtype.

— Treated like adult RCC with nephrectomy ± targeted therapy.

— Benign cystic lesions; cystic nephroma can mimic cystic Wilms (cystic partially differentiated nephroblastoma).

— Precursor lesions found in ~1% of infant kidneys and in ~40% of Wilms tumor kidneys; mandate close surveillance.

Key distinction: Wilms displaces vessels and stays renal-bound; neuroblastoma encases vessels and crosses the midline with calcifications and elevated catecholamines. This vessel-relationship pattern is one of the most reliable imaging clues on board imaging stems.

Neuroblastoma (most important differential):

Mesoblastic nephroma:

Clear cell sarcoma of the kidney (CCSK):

Rhabdoid tumor of the kidney:

Renal cell carcinoma:

Multicystic dysplastic kidney / cystic nephroma:

Nephrogenic rests:

Key Differentials — Other-Category Abdominal Masses

— Most common pediatric liver malignancy, ages 6 months–3 years.

— RUQ mass, markedly elevated AFP.

— Associated with Beckwith-Wiedemann and familial adenomatous polyposis — overlaps with Wilms predisposition.

— Rapidly growing abdominal mass, often ileocecal; B symptoms (fever, weight loss, night sweats).

— Tumor lysis on presentation; elevated LDH and uric acid.

— Pelvic or midline mass; elevated AFP and/or β-hCG.

— Bladder/prostate/vaginal origin; hematuria, urinary obstruction, vaginal bleeding ("sarcoma botryoides").

— Hydronephrosis from UPJ obstruction — cystic on US, not solid.

— Polycystic kidney disease (ARPKD) — bilateral, cystic, often with hepatic involvement.

— Stool-filled colon, distended bladder, constipation — benign causes of "abdominal mass" in toddlers; resolve with bowel/bladder emptying.

— Adrenal hemorrhage in neonates — cystic adrenal mass on US, resolves spontaneously.

— Pheochromocytoma — rare in children; hypertension with paroxysms, elevated metanephrines.

Board pearl: A toddler with a palpable abdominal mass plus markedly elevated AFP = hepatoblastoma, not Wilms. AFP is not a Wilms tumor marker — if the vignette emphasizes AFP, redirect to liver. Conversely, elevated urine catecholamines = neuroblastoma, and monoclonal gammopathy or lytic bone lesions = not pediatric — reconsider the entire framing.

Hepatoblastoma:

Lymphoma (Burkitt and other NHL):

Germ cell tumors (sacrococcygeal teratoma, ovarian teratoma):

Rhabdomyosarcoma (genitourinary or retroperitoneal):

Splenomegaly or hepatomegaly from leukemia, storage disease, or portal hypertension — diffuse organomegaly rather than discrete mass.

Benign mimics:

Adrenal causes:

Survivorship — Long-Term Plan and Secondary Prevention

— Chest imaging (CT or X-ray depending on protocol/risk) and abdominal ultrasound every 3 months × 2 years, then every 6 months to 5 years, then annually — most relapses occur within 2 years of diagnosis.

— Contralateral kidney surveillance ultrasound continues longer in predisposition syndromes.

— Echocardiogram at end of therapy, then per Children's Oncology Group Long-Term Follow-Up guidelines: every 2–5 years based on cumulative dose, age at treatment, and chest radiation.

— Counsel on heart-healthy lifestyle, avoid cardiotoxic substances (cocaine, anabolic steroids).

— Pre-pregnancy echo in female survivors.

— Annual BP, urinalysis for proteinuria, serum creatinine/eGFR.

— ACE inhibitor or ARB for proteinuria or hypertension.

— Avoid nephrotoxins (chronic NSAIDs, aminoglycosides when alternatives exist).

— Adequate hydration; treat UTIs promptly.

— Breast cancer screening with annual MRI + mammography starting at age 25 or 8 years after chest radiation (whichever later) if chest RT received.

— Skin exam annually for in-field skin cancers.

— Colonoscopy starting at age 30 or 10 years after abdominal RT if abdominal radiation received.

— Thyroid exam annually if neck in radiation field.

— Resume routine immunizations 3–6 months after completing chemotherapy.

— Live vaccines (MMR, varicella) held until immune recovery confirmed.

— Annual influenza vaccine for patient and household contacts.

— HPV vaccine on schedule.

Step 3 management: Every childhood cancer survivor needs a written survivorship care plan transferred to their PCP and (eventually) adult provider, listing cumulative chemo doses, radiation fields, and a personalized surveillance schedule. Failure to transfer this plan is a frequent root cause of preventable late morbidity.

Cancer surveillance after completion of therapy:

Cardiac late effects (anthracycline exposure):

Renal preservation in solitary-kidney survivors:

Second-malignancy screening:

Vaccinations:

Fertility counseling: discuss reproductive risks with adolescents and parents; refer to fertility preservation if higher-intensity regimens are planned.

Follow-Up, Monitoring, and Family Counseling

— Weekly CBC, CMP during chemotherapy cycles.

— Pre-cycle assessment of organ function (LFTs before dactinomycin, echo trending before each major doxorubicin milestone, audiology before carboplatin).

— Growth, weight, nutrition, and developmental milestones at every visit.

— Clinical exam, BP, weight every 3 months.

— Abdominal US and chest imaging every 3 months × 2 years.

— Then taper to every 6 months through year 5, then annually.

— Physical and occupational therapy for vincristine neuropathy or deconditioning.

— Speech/feeding therapy if mucositis or radiation-related dysphagia.

— Neuropsychological testing before school re-entry, especially after intensive therapy or CNS treatment.

— Individualized Education Plan (IEP) or 504 plan for school accommodations.

— Anticipatory guidance on neutropenic precautions, fever protocols, central line care.

— Sibling support — siblings of cancer patients have increased anxiety/depression rates.

— Genetic counseling for predisposition syndromes — sibling surveillance, future pregnancies.

— Financial counseling, insurance navigation, school liaison.

— Recognize and immediately report fever ≥38.3°C or ≥38.0°C sustained 1 hour, central line redness/drainage, lethargy, bruising, or hematuria.

— Strict hand hygiene; avoid sick contacts during neutropenia.

— Sun protection (radiation-treated skin and chemo photosensitivity).

— No live vaccines during therapy and 3–6 months after.

— Pediatric oncologist as quarterback; PCP for routine well-child care, immunizations, growth.

— Warm handoff to long-term follow-up clinic at 2–5 years post-therapy, then to adult survivorship clinic in late adolescence.

Board pearl: Most Wilms relapses occur within 2 years of diagnosis, driving the front-loaded every-3-month imaging schedule. Late relapse is rare but possible — annual surveillance through 5+ years is standard. Knowing this timeline lets you correctly choose follow-up intervals on management-decision items.

Active treatment monitoring cadence:

Post-treatment surveillance (first 2 years — highest relapse risk):

Rehabilitation and developmental support:

Family and psychosocial counseling:

Patient/family education points:

Coordination of care:

Ethical, Legal, and Patient Safety Considerations

— Parents/legal guardians provide informed consent; the child provides age-appropriate assent (generally age ≥7).

— Disclose all major risks: surgical bleeding, anesthesia, anthracycline cardiotoxicity, infertility, second malignancies, and protocol-specific late effects.

— Provide written summary in family's preferred language with certified medical interpreter — ad hoc family interpretation is a recognized safety failure.

— Most US children with Wilms are enrolled on Children's Oncology Group protocols. Enrollment requires separate consent with explicit voluntariness — no coercion, clear right to withdraw without affecting standard care.

— If parents refuse curative therapy for a highly curable disease (Wilms has ~90% survival), this may rise to medical neglect.

— Engage palliative care, ethics committee, social work, and — if unresolved — child protective services and court order for treatment. State laws vary; document all conversations and good-faith engagement.

— Suspected abuse or neglect (including treatment refusal causing imminent harm) must be reported.

— Bruising/petechiae from thrombocytopenia must be documented carefully to avoid misattribution to abuse — and conversely, suspicious patterns not explained by disease must still be reported.

— Handoffs between pediatric oncology, surgery, radiation oncology, and PCP — use structured handoff tools (e.g., SBAR, I-PASS).

— Discharge after nephrectomy: verify pain plan, follow-up appointments, when to return for fever or bleeding, vWD precautions if applicable.

— Transition to adult survivorship care in late adolescence — written survivorship plan must accompany the patient.

— Adolescent survivors have evolving rights to confidential discussions about fertility, sexuality, and mental health.

— Ensure access to a COG-affiliated center regardless of insurance; Medicaid coverage and travel/lodging support are part of the care plan.

Step 3 management: When parents refuse chemotherapy for a curable pediatric cancer such as Wilms, the correct sequence is engage interpreter and second opinion → involve social work, ethics, and palliative care → notify hospital legal/risk management → file CPS report and seek court-ordered treatment if refusal persists. Continuing to negotiate while disease progresses is not acceptable.

Informed consent in pediatric oncology:

Clinical trial enrollment:

Refusal of recommended therapy:

Mandatory reporting:

Transition-of-care safety risks (a Step 3 favorite):

Privacy and adolescent confidentiality:

Equity and access:

High-Yield Associations and Rapid-Fire Clinical Facts

— WT1 (11p13) → WAGR (deletion) and Denys-Drash (missense).

— WT2 (11p15) → Beckwith-Wiedemann.

— CTNNB1, WTX, TP53 (anaplastic), REST, CTR9 → additional driver mutations.

— LOH 1p and 16q, 1q gain → adverse prognostic markers, intensified therapy.

— WAGR = Wilms + Aniridia + GU anomalies + Range of developmental delay.

— Denys-Drash = Wilms + diffuse mesangial sclerosis + male pseudohermaphroditism.

— Frasier syndrome = Wilms (less common, gonadoblastoma more typical) + FSGS + 46,XY DSD; WT1 intron 9 splice mutation.

— Beckwith-Wiedemann = Wilms + hepatoblastoma + macroglossia + omphalocele + hemihypertrophy + neonatal hypoglycemia.

— Wilms: intrarenal, displaces vessels, does not cross midline, rare calcifications.

— Neuroblastoma: extrarenal/adrenal, encases vessels, crosses midline, calcified.

— Normal urine HVA/VMA → not neuroblastoma.

— Acquired vWD in ~8% — check before surgery.

— AFP normal in Wilms — if elevated, think hepatoblastoma.

— Stage I/II FH → VA (vincristine + dactinomycin), no RT.

— Stage III/IV FH → VAD (add doxorubicin) + RT.

— Anaplastic or high-risk biology → intensified multi-agent regimens + RT.

— Bilateral → neoadjuvant chemo + nephron-sparing surgery.

— Overall survival ~90% for FH; ~50–70% for diffuse anaplasia.

— Lungs = #1 metastatic site; liver = #2.

— Predisposition syndromes → abdominal US every 3 months until age 7–8.

— Beckwith-Wiedemann adds AFP every 3 months until age 4 for hepatoblastoma.

Board pearl: "Aniridia + GU anomaly + abdominal mass = WAGR; macroglossia + omphalocele + hemihypertrophy + abdominal mass = Beckwith-Wiedemann; nephrotic syndrome in infancy + ambiguous genitalia + abdominal mass = Denys-Drash." Memorizing these three triads answers the majority of syndromic Wilms questions on the exam.

Genetics rapid-fire:

Syndrome → tumor associations:

Imaging rapid-fire:

Lab rapid-fire:

Treatment rapid-fire:

Outcome rapid-fire:

Surveillance rapid-fire:

Board Question Stem Patterns

— "A 3-year-old previously healthy girl is brought in after her mother felt a firm, painless lump in her left abdomen while bathing her. She is afebrile, growing well, BP 118/78. Exam reveals a smooth, non-tender left flank mass that does not cross the midline." → Wilms tumor; next step abdominal ultrasound (then CT abdomen/chest), not biopsy.

— "Ill-appearing 2-year-old with weight loss, bone pain, periorbital bruising, and a midline-crossing calcified abdominal mass" → neuroblastoma; order urine HVA/VMA, MIBG scan.

— Contrast with the well-child Wilms presentation.

— "Newborn with macroglossia, omphalocele, and hemihypertrophy" → Beckwith-Wiedemann → abdominal US every 3 months until age 7–8 + AFP for hepatoblastoma until age 4.

— "Toddler with aniridia and hypospadias" → WAGR → same surveillance.

— "Surgeon performed nephrectomy without lymph node sampling" → automatic upstaging to stage III → requires abdominal radiation. Lesson: always sample nodes.

— "Capsule ruptured during resection" → stage III → adjuvant RT and three-drug chemo.

— "Child on dactinomycin develops painful hepatomegaly, ascites, thrombocytopenia, weight gain" → veno-occlusive disease (sinusoidal obstruction syndrome).

— "Child on vincristine develops hyponatremia with concentrated urine" → SIADH.

— "Adolescent Wilms survivor presents with dyspnea and reduced ejection fraction 10 years later" → anthracycline cardiomyopathy.

— Renal mass at 2 months → mesoblastic nephroma.

— Renal mass at 3 years → Wilms.

— Renal mass at 14 years → RCC, clear cell sarcoma, or rhabdoid tumor.

— Parents refuse chemo for stage II FH Wilms → engage ethics, social work; ultimately seek court order if refusal persists, given >90% curability.

Key distinction: The single most discriminating board cue is child's general appearance: a thriving toddler with an incidentally discovered, midline-respecting flank mass is Wilms; a systemically ill child with a calcified, midline-crossing mass and elevated catecholamines is neuroblastoma.

Pattern 1 — The classic well-child mass:

Pattern 2 — Wilms vs neuroblastoma:

Pattern 3 — Syndromic Wilms:

Pattern 4 — Staging trap:

Pattern 5 — Intraoperative spill:

Pattern 6 — Chemotherapy toxicity:

Pattern 7 — Differential by age:

Pattern 8 — Refusal of therapy:

One-Line Recap

Wilms tumor is the most common pediatric renal malignancy, classically presenting in a well-appearing 2–5-year-old with an asymptomatic, midline-respecting flank mass, worked up with abdominal ultrasound and CT chest/abdomen, and treated with upfront radical nephroureterectomy plus lymph node sampling followed by stage- and histology-tailored chemotherapy (vincristine/dactinomycin ± doxorubicin) and selective radiation, with overall survival approaching 90%.

Board pearl: If the stem features a thriving toddler whose parent felt a painless lump while bathing the child — order the ultrasound, protect the abdomen, and march down the Wilms pathway; deviations from this script (sick child, midline-crossing mass, elevated catecholamines, elevated AFP, infant under 6 months) point to neuroblastoma, hepatoblastoma, or mesoblastic nephroma instead.

Recognize the patient: thriving toddler, painless flank mass, mass does not cross midline, normal urine catecholamines, age 2–5; screen for WAGR, Denys-Drash, Beckwith-Wiedemann, isolated hemihypertrophy (US every 3 months until age 7–8).

Workup pearls: abdominal US with Doppler first (assess IVC), then CT chest + abdomen/pelvis, baseline labs including CBC, CMP, urinalysis, coags, vWF panel, urine HVA/VMA, echocardiogram; avoid biopsy and avoid deep palpation — both can upstage the tumor.

Management framework: COG = surgery first (radical nephroureterectomy + node sampling) with neoadjuvant chemo reserved for bilateral disease, solitary kidney, IVC thrombus above hepatic veins, or unresectable tumor; node sampling and capsule integrity are non-negotiable because both spill and unsampled nodes upstage to stage III.

Long-term care: front-loaded surveillance for relapse (every 3 months × 2 years), lifelong anthracycline cardiac monitoring, renal preservation in solitary-kidney survivors, second-malignancy and breast cancer screening after radiation, and a structured survivorship care plan transitioning from pediatric to adult care.