PEDIATRIC ONCOLOGY

Pediatric GU Review

UCSD Pediatric UrologyGeorge Chiang MD

Sara Marietti MD

Outlined from The Kelalis-King-Belman Textbook of Clinical Pediatric Urology 2007

(not for reproduction, distribution, or sale without consent)

Wilm’s Tumor• 6% of childhood neoplasms• Incidence: 6-7:1,000,000 children• Black>White>Asian• 75% are >5yo, peak age is 3-4yo in

sporadic, unilateral, younger in bilateral/syndromes–5% bilateral–12% multifocal

Wilm’s Presentation• Painless abdominal mass in healthy

appearing child

• <15% have hematuria

• HTN relatively uncommon–More commonly seen with congenital

mesoblastic nephroma

Wilm’s Imaging• For surgical planning

–Bilateral–Solitary or abnormal contralateral kidney– IVC extension

• Initially Renal U/S

• F/U CT Chest/Abdomen

Wilm’s Genetics• 1-2% AD with incomplete penetrance &

variable expression• 15-20% other genetic inheritance• Syndromes

– WAGR – WT1 gene (11p13)– Beckwith-Weideman – WT2 gene (11p15)– Denys-Drash – WT1 gene (11p13)– Hemihypertrophy– P53, FWT1 (17q), FWT2 (19q), 16q, 1p

Wilm’s: Associated Anomalies• Somatic Overgrowth

– Hemihypertrophy alone (33%)– BWS (3-5%)

• Exophthalmos, gigantism,hemihypertrophy

– Perlman• Organomegaly, macrosomia, polyhydramnios

• Without somatic overgrowth– Sporadic aniridia (33%),– WAGR (33%)– Denys Drash– Hypospadias, cryptorchidism

Wilm’s Staging• I – Confined, total resection

• II – Outside capsule (bx, spill), total resection

• III – Incomplete resection, massive spill, + LN

• IV – Distant mets (hematogenous)

• V – Bilateral tumors

Wilm’s Pathology• Variants

– Favorable histology – triphasic pattern– Unfavorable/Anaplastic - 10% but 60% of deaths

• Nephroblastomatosis – precursor lesion– 45% in unilateral WT, 100% in bilateral WT

• Nephrogenic Rests– ILNR (intralobar), less common, assoc with

syndromes– PLNR (perilobar), present later, BWS and hemihyp

Wilm’s Treatment• Unilateral

– Contralateral exploration no longer mandatory– Ipsilateral Nx with LN sampling

• Bilateral – Upfront chemo without bx is now acceptable– Bx inconclusive tumors unless small lesion

amenable to partial Nx– Nx only if known UH or chemo failure– Partial if >2/3 of kidney can be preserved– Prognosis = higher unilateral WT

Wilm’s Surgery• 11% complication rate

– Hemorrhage and bowel obstruction most common

• Spillage & rupture increases local recurrence by factor of 6

• Partial Nx– NWTSG: bilateral WT, nephroblastomatosis,

solitary kidney, renal insufficiency• Excellent survival and low recurrence rates in pt with

bilateral WT and RCC experience in adults

Stage XRT Chemo

I/II FH - EE-4A

III/IV FH, I UH + DD-4A

II-IV, focal anaplasia

+ DD-4A

II-IV, diffuse anaplasia

+ Regimen I

I-IV CCSK/rhabdoid

+ Reg. RTK

EE 4A = dactinomycin, vincristineDD 4A = dactinomycin, vincristine, doxorubicinReg I = dactinomycin, vincristine, doxorubicin, cyclophosphamide, etoposideReg RTK = carboplatin, etoposide, cyclophosphamide

Other Renal Neoplasms• CCSK

– Bone metastasizing tumor of childhood (50%)– Survival can be as high as 90% with doxorubicin

• Rhabdoid– Infants, dismal prognosis

• Congenital Mesoblastic Nephroma– Infants >3mos– Nx usually curative– Cellular variants and incomplete resection can

behave aggressively

Renal Cell Carcinoma• Mean age – 5yo

• <5% of all RCC

• Better survival than adults – 75% 5yr

• Increased frequency in survivors of WT & neuroblastoma–Possible genetic predisposition?

Neuroblastoma• 8-10% of childhood neoplasms• Neural crest cells: form SNS and adrenal

medulla• VMA screening in Japan & Canada has

led to increased dx but no change in survival

• Spontaneous regression–Neuroblastoma in situ, <3 mos of age

NB - Presentation• 65% retroperitoneal• 40% adrenal• 4% presacral – can compress bladder and

cause voiding symptoms• Often cross midline• Sickly appearance• 70% present with mets

– Liver, soft tissue, bone, BM

NB - Diagnosis• Abdominal imaging as with WT

– MIBG scan may be helpful in equivocal cases– Calcifications are common

• Labs– BM aspirate + in 70%– Spot urine VMA + in 70%

• 24 hr urine for catecholamine metabolites + in 95%

Poor Prognosis• Diploid responds more poorly than

hyperdiploid

• N-myc amplification– >40% of pts with advanced dz and <10% with low

stage dz

• Gains at 17q locus

• TRK-A gene expression

• Elevated serum ferritin – large or rapidly progressive tumor

Evans Staging• I – confined to structure of origin

• II – tumor extension w/o crossing midline, +/- LN

• III – extension across midline, +/- LN

• IV – remote spread

• IVS – Stage I or II with mets to liver, skin, BM

International Neuroblastoma Staging System

• I – localized with complete resection• IIa – Localized w/o complete gross resection• IIb – + Ipsilateral LN, - Contralateral LN• III – Unresectable local tumor &/or contralateral LN • IV – Distant hematogenous or LN mets• IV S – Stage I or II tumor with spread to skin, liver, or

BM (less than 1yo)

NB - Therapy• Surgery: both diagnostic and therapeutic

–Favorable Dz – low risk, stage I and II• Excision• 90% survival

– Intermediate Dz – stage III• Excision and chemo

–Stage IV• Biopsy and chemo• Possible BM transplant

–Stage IV S • Observation, >90% survival and regression

Rhabdomyosarcoma• Most common soft tissue sarcoma

• 10-15% of solid peds malignancies

• M>F, Black>White

• Bimodal: 2-6yrs and 15-19yrs

• Spread: local>lymphatic (18%)>hematogenous (10%)

RMS: Pathology• Mesenchymal origin with skeletal muscle

differentiation

• Embryonal (ERMS): 90%, predominates in younger pts, GU and ENT sites–Sarcoma botryoides – polypoid, found in hollow

organs–74% 5 yr survival

• Alveolar (ARMS): older, extremities

• Pleomorphic (PRMS)

RMS: Presentation• Site dependent• Bladder

– Mean age – 3.5 yrs– 2:1 M:F– Palpable mass more common than hematuria

• Prostate – Mean age – 3.5 yrs– BOO +/- hydro

• Female– Vagina <2yrs, Vulva 1-19yrs, Uterus - adolescent

RMS: Evaluation and Therapy• MRI

• Surgery – primarily diagnostic with tx aimed at organ preservation

• Chemo – mainstay of tx with diminished role for XRT–Cures microscopic dz

Post Op Grouping for RMS• Group 1: localized dz, completely excised, no micro

residual– A: confined to site of origin– B: infiltrating beyond site of origin

• Group 2: total gross resection– A: microscopic local residual– B: regional dz with involved LN, no micro residual– C: microscopic local or nodal residual

• Group 3: incomplete resection or bx with gross residual

• Group 4: distant mets

Post Op Grouping for RMS• Eliminated bias by grouping pts based

on completeness of resection

• 80% of bladder/prostate are group III

• >50% of non-bladder/prostate are group I

RMS: Risk Stratification• Low risk: most vaginal, paratesticular

primaries, embryonal primaries with gross total resection, no mets

• Intermediate risk: most bladder/prostate primaries, non-metastatic embryonal, alveolar, or undiff tumors with gross residual dz, metastatic embryonal tumors <10yo

• High risk: metastatic embryonal tumors >10yo, metastatic alveolar or undiff tumors

RMS: Chemotherapy• VAC (vincristine, dactinomycin, cyclophosphamide)

– Cheaper and less toxic, equally effective when compared to VIE (vincristine, ifosfamide, etoposide) or VAE (vincristine, dactinomycin, and etoposide)

• IRS V – Low risk – VAC vs VA +/-XRT– Intermediate risk – XRT/VAC vs XRT/VAC alt with VC +

topotecan– High risk – XRT/VAC + Irinocetan– Abandoned BM transplant

Testicular Tumors• Only 1-2% of pediatric neoplasms• Most are <2 yrs of age• Mets <15%:

– LN 28%– Hematogenous 40%– Both 20%

• Tumor proportion– Yolk sac 60-80% over 1st 2-3 yrs

Yolk Sac Tumors: Diagnosis• Scrotal mass

– 10% associated hydrocele– 3% - hx of trauma

• >85% are localized (Stage I)

• U/S if exam difficult

• Abd/Chest CT for staging along with AFP

Yolk Sac Tumors: AFP• Elevated in >90% of yolk sac tumors• T1/2 = 5 days (most of the time levels will

return to nl within 1 month of orchiectomy)• Levels normally elevated in neonates

– 50,000 at birth– 10,000 by age 2 weeks– 300 by age 2 months– Adult levels by age 9 months

• Liver dysfunction will also cause elevated AFP

YST: Staging• I – completely resected with nl AFP

degradation and – Xray staging

• II - + microscopic margins, persistent AFP elevations, + RPLN <2cm

• III - + RPLN >2cm w/o hematogenous mets

• IV - + distant/hematogenous mets

YST: Treatment• Surgery

– Inguinal orchiectomy –Routine RPLND not done

• Unknown AFP at dx, persistent RP mass p chemo, elevation of AFP with neg imaging p chemo

• Chemo–BEP

Teratoma• Usually mature and well differentiated

• Typically benign in children <2

• U/S – heterogeneous intratesticular mass with internal echoes

• Rx: Enucleation vs orchiectomy–Complete excision is curative

• No need for chemo/RPLND

Leydig Cell Tumor• Most common gonadal stromal cell tumor

– Peak 4-5 yrs

– 10% of precocious puberty <9yo

– Unilateral and benign

• Classic presentation = precocious puberty, testis mass, and elevated serum T/urine KS– Diff from pituitary tumors by low LH and FSH

• Path: Reinke’s crystals rare in children (40% adults)

• Rx: enucleation if possible

Gonadoblastoma• Pts with an abnormal gonad whose

karyotype contains Y chromosome–80% phenotypic females with 46XY–22% streak, 18% dysgenetic, 60% indeterminate

• Bilateral in 10-33%• Benign tumors – 10-60% will progress to

malignant dysgerminomas after puberty• Rx: gonadectomies early

Paratesticular RMS• Typically histologically favorable (ERMS) but can be

LN + in up to 30% at dx• Pts should get CXR, CT, bone scan, and BM bx• Routine RPLND no longer recommended if imaging –

and complete resection– ? Benefit in pts >10yo b/c of poor prognosis in older group– Sampling if bulky mass p chemo

• XRT: no longer routine if imaging – for LN• Survival >95% with chemo alone in children <10yo

Juvenile Granulosa Cell Tumor• 27% of neonatal testicular tumors• Commonly appear as cystic, painless

testicular masses• Almost exclusively appear in 1st year of life

and most are by 6 mos• Considered hormonally active and benign• Rarely metastasize• Treated by inguinal orchiectomy

A newborn boy has a large, firm, left flank mass palpated on routine physical examination. An ultrasound shows a solid renal mass. The most likely diagnosis is:

a) Neuroblastoma

b) Mesoblastic nephroma

c) Hemorrhage into a hydronephrotic kidney

d) Mesonephric hamartoma

e) Wilm’s tumor

A 14 year old girl has gross hematuria. She is thin, chronically ill, and has an erythematous rash on her face and tongue. Radiologic studies show bilateral renal masses. Percutaneous needle biopsy shows both renal cell carcinoma and hamartoma. She most likely has:

a) Neurofibromatosis

b) Sturge-Weber syndrome

c) VHL

d) Tuberous sclerosis

e) sarcoidosis

A 4 month old boy undergoes a left radical orchiectomy for a testicular mass. Pathology reveals a yolk sac tumor confined to the testes. CT scans of the chest and abdomen are negative. Preoperative serum AFP was 500 ng/ml. 2 months later, the serum AFP is 25 ng./ml. The next step is:

a) Modified RPLND

b) Combination chemotherapy

c) Scrotal ultrasound

d) Surveillance

e) Retroperitoneal lymph node sampling+

The appropriate maintenance IV fluid for a 14 kg child is:

a) 25 cc/hr of ½ NS

b) 50 cc/hr of ¼ NS

c) 50 cc/hr of NS

d) 75 cc/hr of ¼ NS

e) 75 cc/hr of ½ NS

A 14 year old boy has a painless mass above the right testis. The mass is removed through the groin and reveals a completely resected paratesticular rhabdomyosarcoma. His abdominal CT scan is normal. The next step is:

a) Repeat CT in 3 months

b) Adjuvant chemo with doxorubicin and alkylating agents

c) Retroperitoneal radiation

d) Ipsilateral RPLND

e) Bilateral RPLND

A 4 year old 15 kg boy with von Willebrand’s disease undergoes nephrectomy after receiving IV DDAVP. Postoperative fluids were D51/2NS at 65 cc/hr. He is disorientated POD#1. Urine output over the past eight hours is 90cc. He is afebrile, pulse is 90, and BP is 90/60. The most likely cause for disorientation is:

a) Sepsis

b) Hyponatremia

c) Hypoglycemia

d) Adrenal insufficiency

e) Postop hemorrhage

A one-month old boy undergoes left radical orchiectomy for an endodermal sinus (yolk sac) tumor. Chest and abdominal CT scans are normal. Preoperative AFP is 2600 ng/dl and postoperative levels at one and two months are 330 and 90 ng/dl (normal<10). The next step is:

a) Bone scan

b) Ultrasound of right testis

c) Multiagent chemotherapy

d) RPLND

e) Repeat AFP in one month

A 10 month old girl undergoes a left nephrectomy for Wilms’ tumor. The right kidney is normal at the time of surgery. Pathology reveals the presence of perilobar nephrogenic rests. She is at increased risk for:

a) Nephrotic syndrome

b) Renal failure

c) Metachronous Wilms’ tumor

d) Local recurrence

e) Metastatic disease

The site of origin with the worst prognosis in rhabdomyosarcoma is :

a) Uterus

b) Prostate

c) Vagina

d) Spermatic cord

e) bladder

A newborn boy with anemia and jaundice has an abdominal u/s that shows a left suprarenal mass. A follow-up ultrasound at one month reveals that the mass is slightly smaller, but is now calcified. Serum AFP and urinary VMA are normal. The next step is:

a) Needle aspiration

b) Abdominal CT scan

c) Abdominal MRI scan

d) Exploratory laparotomy

e) Observation

The most important prognostic factor in a patient with Wilm’s tumor is:

a) Age of the patient

b) Lymph node status

c) Intraoperative spillage

d) Tumor histology

e) bilaterality

An 8 year old boy with ALL undergoes chemotherapy. His urine output during the last 24 hrs is 50 cc. Serum creatinine is 2.1 and BUN 40 and uric acid 8.5. Renal ultrasound demonstrated normal sized kidneys with no hydronephrosis and increased echogenicity. The next step is:

a) Isotope renogram

b) Renal biopsy

c) Retrograde pyelography

d) Allopurinol

e) Hydration and urinary alkalinization

A 4 kg, seven day old boy undergoes a left nephrectomy. The blood loss is 40 cc. 2 hours postoperatively, the BP is 70/40 mmHg, pulse is 125, and hemoglobin is 11. He has made 8 cc of urine since surgery. The most appropriate management is:

a) Transfuse 10 cc/kg PRBC

b) Give 10 cc/kg 5% albumin

c) Bolus with 100 cc LR

d) Place a central venous catheter

e) Continue maintenance IVF

A 2 year old girl has a palpable abdominal mass. CT scan demonstrates a 5 cm enhancing left renal mass. The right kidney is normal. The most appropriate treatment is:

a) Percutaneous biopsy and chemotherapy

b) Left radical nephrectomy and postoperative chemotherapy

c) Left partial nephrectomy

d) Left radical nephrectomy and right renal biopsy

e) Preoperative chemotherapy and left radical nephrectomy