Oncology-Pediatrics 1

Front 1

1.)What is the most common extracranial solid tumor in children?

2.)What percent of all childhood tumors does this comprise?

3.)What are the most common ages of pediatric patients with neuroblastoma?

4.)What is the most median age at diagnosis?

Back 1

1.)Neuroblastoma,

2.)8-10% of all childhood cancers.

3.) 50% occur in children younger than 2 years old. 75% are diagnosed by age 4.

4.)The median age at diagnosis is 21 months

Front 2

1.)From which cells does neuroblastoma arise?

2.)Explain the concept of “in situ” neuroblastoma.

Back 2

1.)From neural crest cells that form the adrenal medulla and sympathetic ganglia
May occur anywhere along sympathetic chain within neck, thorax, retroperitoneum, pelvis or adrenal gland (75% in retroperitoneum: 50% adrenal and 25% paravertebral ganglia)

2.)Small nodules of neuroblasts found incidentally in the adrenal gland (indistinguishable from neuroblastoma). Studies have shown that these are present in all fetuses and spontaneously regress. Neuroblastoma on prenatal ultrasound therefore offers a favorable prognosis.

Front 3

1.)Is neuroblastoma hereditary?

2.)Is there a way to tell if the particular case is hereditary or spontaneous?

Back 3

1.)Some cases are autosomal dominant.

2.)> 20% of this familial variant will have bilateral adrenal or multifocal primary tumors (unusual in spontaneous cases)

Front 4

What are the important prognostic factors with respect to neuroblastoma?

Back 4

Clinical Variables are:
Age: Children diagnosed <1yo have better prognosis
Site: Nonadrenal primary tumors with better prognosis
Stage: Stages 1, 2, and 4S have better prognosis

Biologic Variables:
Deletion of short arm chrom. 1 (70-80% of cases) (bad prognosis)
Aneuploidy of tumor DNA (good prognosis)
Amplification of N-myc oncogene (bad prognosis)

Front 5

Describe the histopathologic classification scheme of neuroblastoma. Does this aid in predicting prognosis?

Back 5

Shimada classification
Stroma Poor (poor prognosis in general)
Favorable (young age of diagnosis)
Unfavorable (older age at diagnosis)
Stroma Rich (favorable prognosis)
Nodular (least favorable of this group)
Intermixed
Well-differentiated

Front 6

1.) What is the organ of Zuckerkandl?

2.) What percentage of neuroblastomas will arise from this organ?

Back 6

The organ of Zuckerkandl (also known as paraaortic bodies) is a chromaffin body derived from neural crest located at the bifurcation of the aorta or at the origin of the IMA.

2.) 4% of neuroblastomas will arise here (pelvic neuroblastoma)

Front 7

1.)Describe the clinical findings in neuroblastoma.

2.)What percent of patients diagnosed with neuroblastoma have metastases at the time of diagnosis?

Back 7

1.) The majority will have abdominal pain or palpable mass
Many will have manifestations of metastasis (e.g. bone/joint pain, periorbital ecchymosis, cough/dyspnea, neurologic deficits from cord compression)

2.) 70% of patients will have metastases at diagnosis

Front 8

Describe 3 paraneoplastic syndromes associated with neuroblastoma.

Back 8

Catecholamine release similar to pheochromocytoma à paroxysmal HTN, palpitations, flushing, headache
Vasoactive intestinal peptide (VIP) release à watery diarrhea and hypokalemia
Acute myoclonic encephalopathy à myoclonuse, opsoclonus, ataxia

Front 9

T/F: Acute myoclonic encephalopathy is a foreboding sign of neuroblastoma progression.

Back 9

FALSE: Favorable oncologic prognosis, but w/ prolonged neurologic impairment, LD & dev delay are frequent
Treat with ACTH, IV gamma globulin and cyclophosphamide

Front 10

What laboratory studies are ordered in diagnosing neuroblastoma?

Back 10

Urinary catecholamine metabolites (VMA and HVA) found in 90-95%; can monitor for decrease w/treatment
CBC (to assess for anemia from bone marrow involvement) followed by bone marrow biopsy

Front 11

The site of origin with the worst prognosis in patients with rhabdomyosarcoma is?

Back 11

*The prostate.

Front 12

What imaging studies are important when diagnosing neuroblastoma?

Back 12

Plain films may demonstrate a calcified abdominal or posterior mediastinal mass
Bone scintigraphy and skeletal survey to look for cortical bone metastases
MIBG scintigraphy to determine extent of disease and recurrence (unclear impact on treatment)
U/S, CT, or MRI to offer information about local extent of tumor

Front 13

Japan has been screening for neuroblastoma for over 20 years and their studies show uniformly favorable survival (>97%) in these patients. Is this evidence that we should screen our kids?

Back 13

No- two prospective trials have shown no benefit (no improvement in survival). Those diagnosed with urine screening already have a favorable prognosis and many spontaneously resolve without therapy

Front 14

Describe the International Neuroblastoma Staging System

Back 14

Stage 1: localized tumor with complete gross excision w/ or w/o microscopic disease, negative ipsilateral LN (nodes attached to tumor may be positive)
Stage 2A: localized tumor without complete gross excision, ipsilateral LN negative microscopically
Stage 2B: localized tumor with or w/out complete gross excision with + ipsilateral LN, enlarged contralateral LN must be negative microscopically
Stage 3: Unresectable unilateral tumor infiltrating ACROSS midline, with or without regional LN involvement, localized unilateral tumor with contralateral LN, or midline tumor with bilateral extension or by LN involvement
Stage 4: Any primary tumor with dissemination to distant LN, bone, marrow, liver, skin and/or other organs
Stage 4S: Localized primary tumor with dissemination (limited to skin, liver, and/or <10% marrow involvement) in infants <1yo, with no radiographic evidence of bone mets

Front 15

We understand that Stage IV-S confers an improved prognosis. Are there any cases in which this is not true?

Back 15

Elevated serum neuron-specific enolase (>100nmol/mL), ferritin (>280ng/mL), and urinary dopamine levels (>2500nmol/mmol Cr)
N-myc amplification and chromosome 1p deletion

Front 16

Briefly describe the treatment for Neuroblastoma

Back 16

Low-Risk Disease (Stages 1, 2, and 4-S)
Surgery is curative if fully resected in Stages 1 and 2
Chemotherapy only if recurrent (exception: N-myc amplification and unfavorable histology)
Stage 4-S may be observed without need for surgery, may consider limited chemo and hepatic radiotherapy if symptomatic
High-Risk Disease (Stages 3 and 4)
Defer surgery until after chemo shrinks the tumor (13-18 wks)
Radiotherapy may be used for local control
After tumor debulking, may attempt autologous marrow transplant
For spinal lesions, chemo first, then laminectomy (avoid radiation)

Front 17

How would you go about diagnosing pheochromocytoma in a child?

Back 17

Plasma metanephrine levels
CT or T2-weighted MRI will detect most lesions
If extra-adrenal location, MIBG is very sensitive

Front 18

What is the most common soft tissue sarcoma in infants and children?

Back 18

Rhabdomyosarcoma (50% of pediatric soft tissue sarcomas and 15% of all pediatric solid tumors)

Front 19

What percent of RMS arises from the GU system? What are the most common organs affected? What is the age of diagnosis of RMS?

Back 19

15-20% arise from GU system.
Most commonly affected are the prostate, bladder, and paratesticular region
Bimodal distribution (peak in first 2 years of life, and again at adolescence), 2/3 present in less than 6 years old

Front 20

What are the three major histologic subtypes of RMS? Which Embryonal sub-type variants are associated with excellent survival? Where does metastatic RMS usually spread? What is the best predictor of outcome for RMS?

Back 20

Embryonal (most common), alveolar, and pleomorphic
Sarcoma botryoides and spindle cell
To the lungs
Tumor stage at diagnosis

Front 21

Describe the difference in spread patterns among the subtypes of RMS?

Back 21

Its either ERMS or ARMS

Embryonal (loss of heterozygosity on chr11 with IGF-II overexpression)
Most common subtype
May occur as solid tumor, in muscle groups, as sarcoma botryoides, or spindle cell (leiomyomatous) in paratesticular region
Alveolar (translocation of chr1 or 2 with 13, expression of PAX3-FKHR)
Occurs mostly in the trunk
Worse prognosis than embryonal with higher local recurrence and spread to regional LN, bone marrow and distant sites
Pleomorphic (considered anaplastic variant of embryonal or alveolar)

Front 22

What familial syndrome is associated with RMS? What mutation is most commonly found?

Back 22

Li-Fraumeni syndrome (association of sarcomas with mothers who have excess premenopausal breast cancer and siblings with increased risk of cancer)
p53 tumor suppressor gene mutation found in all patients

Front 23

Describe the TGNM staging system of RMS.

Back 23

Stage 1: Favorable, nonmetastatic
Stage 2: Unfavorable, small tumor, negative nodes, nonmetastatic
Stage 3: Unfavorable, big tumor or positive nodes, nonmetastatic
Stage 4: Any site, metastatic
T: T1 is confined to site of origin, T2 is fixation to surrounding tissues
G: Histology: G1 (favorable: embryonal, botryoid, spindle), G2 (unfavorable: alveolar, undifferentiated)
N: N0 vs. N1
M: M0 vs. M1

Front 24

How does bladder and prostate RMS differ in location and gross appearance? What is the focus of treatment of bladder and prostate RMS? How do you treat?

Back 24

Bladder: intraluminal mass, usually botryoid at or near trigone; Prostate: solid mass
Focus of treatment is preserving an intact bladder
Treat with chemo/radiation before surgical resection and then partial cystectomy

Front 25

How do paratesticular RMS present? What percentage of RMS is in this location? Where does it arise? What kind of workup should be performed when diagnosing paratesticular RMS? What is current survival rate w/proper treatment of paratesticular RMS?

Back 25

7-10% of RMS arise in the paratesticular area and presents with unilateral painless scrotal swelling or mass distinct from testis
Arises from distal spermatic cord, may invade testis & surrounding structures
CT abdomen/pelvis to evaluate retroperitoneal mets (occurs in 20%), although there is 14% false-negative rate
With proper treatment, the current survival rate is 90%

Front 26

1.) T/F: At diagnosis, the majority of paratesticular RMS are aggressive and high stage.

2.) What is the typical histology?

Back 26

1.) False. 60-80% are stage I

2.) >90% are embryonal histology with good prognosis. Even those with alveolar histology have a better prognosis than alveolar histology at other sites

Front 27

What is the initial surgical treatment of paratesticular RMS? What kind of incision would you make and why? What if a trans-scrotal procedure was performed

Back 27

Radical inguinal orchiectomy because if removed through a scrotal procedure, the risk for local recurrence and non-regional LN spread is increased.
If a trans-scrotal procedure was performed, you should go back and perform an inguinal exploration, removing the remaining spermatic cord and a partial hemiscrotectomy which includes the previous scrotal incision.

Front 28

What is the role of RPLND for paratesticular RMS?

Back 28

The role is controversial but IRS-IV data now indicate that ipsilateral RPLND should be performed for children 10 years and older as part of routine staging prior to starting chemotherapy

Front 29

Where does vaginal RMS arise from?

Back 29

Anterior vaginal wall in area of embryonic vesicovaginal septum (UG sinus)

Front 30

What kind of histology is associated with vaginal/vulvar RMS and is it usually a favorable prognosis?

Back 30

Vaginal usually embryonal or botryoid embryonal histology- favorable
Vulvar usually alveolar histology- but still good prognosis b/c localized

Front 31

What are the prognostic indicators for vaginal and vulvar RMS?

Back 31

Age 1-9 yo
Botryoid histology
Localized disease

Front 32

What is the treatment for vaginal and vulvar RMS?

Back 32

initial course of chemotherapy, possible XRT followed by repeat biopsies
If persistent disease, partial vaginectomy or vaginectomy + hysterectomy

Front 33

What is involved in staging uterine RMS?

Back 33

Biopsy of uterus (usually via D&C)
CT C/A/P
Bone marrow examination
Cystoscopy & Vaginoscopy

Front 34

How is uterine RMS treated?

Back 34

Same as vulvar/vaginal- chemo followed by XRT and delayed local therapy

Front 35

T/F: Wilms’ tumor is the most common extracranial solid tumor of childhood.

Back 35

False, it is the most common primary malignant renal tumor of childhood
Accounts for 6-7% of all childhood cancers, incidence 7-10 cases/million
Neuroblastoma is the most common extracranial tumor of childhhod

Front 36

What is the typical age for Wilms’ Tumor? What percentage have a family history of Wilms’ tumor?

Back 36

Greater than 80% occur in patients less than 5 years old; median age is 3.5 years old
Occurs earlier in male patients and those with bilateral disease
1-2% have a family history of Wilms’ tumor

Front 37

What syndromes are associated with increased incidence of Wilms’ Tumor and how common are they?

Back 37

GU anomalies (hypospadias and/or cryptorchidism)- in 4.5% of Wilms’ cases
Denys-Drash syndrome (male pseudohermaphroditism, renal mesangial sclerosis, and nephroblastoma)
Aniridia- found in 1.1% of Wilms’ cases- especially in WAGR syndrome (Wilms’, Aniridia, Genital anomalies, mental Retardation)
Horseshoe kidney: 7-fold increased risk of Wilms’ in children.
Beckwith-Wiedemann syndrome: excess growth at cellular, organ (macroglossia, nephro/hepatomegaly) or body segment (hemihypertrophy) levels, confers 4-10% risk of nephroblastoma with 20% bilateral

Front 38

What genetic abnormality leads to aniridia (lack of an iris)which links it to Wilms’?

Back 38

Abnormality in PAX6 gene located adjacent to the WT1 gene (associated with Wilms’)

Front 39

Which children should be screened for Wilms’ tumor, and how/when should this be done?

Back 39

aniridia, hemihypertrophy, and BWS (screen with serial renal ultrasound at 3-4 month intervals)

Front 40

What are the two genes that have been associated with Wilms’ tumor and on what chromosomes are they located? What associations do they have?

Back 40

WT1 (chromosome 11p13): associated with WAGR (inactivated WT1 protein) & Denys-Drash syndrome (dysfunctional WT1 protein)
WT2 (chromosome 11p15): associated with BWS

Front 41

What percent of Wilms’ tumors are familial? What genes are responsible?

Back 41

1-2% (earlier age of onset and more often bilateral disease)
FWT1 (at chromosome 17) and FWT2 (at chromosome 19)

Front 42

What are two chromosomal abnormalities with Wilms’ tumors which have been associated with increased risk for tumor relapse and death?

Back 42

Loss of long arm of chromosome 16
Loss of short arm of chromosome 1p

Front 43

Describe the histopathology of Wilms’ tumor and why this affects prognosis.

Back 43

Classic” Wilms’ is Triphasic: islands of compact, undifferentiated blastemal cells, variable epithelial cells and stromal cells
Predominant blastemal pathology is highly aggressive whereas epithelial predominant is least aggressive

Front 44

What patients are more commonly associated with anaplastic histology of Wilms’?

Back 44

Patients older than 5 year old
Associated with resistance to chemo (which is source of aggressiveness)

Front 45

What are the two types of nephrogenic rests (Wilms’ precursor lesions), where are they located and when do these develop embryologically?

Back 45

Perilobar (PLNRs): established late in embryogenesis, only in lobar periphery and sharply demarcated
Intralobar (ILNRs): earlier gestational abnormalities, anywhere in kidney

Front 46

If a patient is known to have nephrogenic rests as well as Wilms’, what do you worry about?

Back 46

Contralateral disease- so annual surveillance is necessary

Front 47

What is nephroblastomatosis?

Back 47

Presence of multiple nephrogenic rests- diffuse overgrowth causes enlargement of the kidney while preserving its shape

Front 48

What hematologic abnormality may be found in 8% of patients with Wilms’ tumor?

Back 48

Acquired von Willebrand’s disease

Front 49

What are the common presenting symptoms associated with Wilms’ tumor?

Back 49

Palpable smooth abdominal mass
Abdominal pain, gross hematuria, fever
Acute abdomen (if tumor ruptures)
HTN (in 25% of cases)

Front 50

What imaging modality provides a definitive diagnosis of Wilms’ tumor? What diagnostic study should be performed first in suspected Wilms’ tumor?

Back 50

None. All solid renal tumors of childhood have the same radiographic appearance.
Renal ultrasound (to determine solid nature of lesion) and doppler to exclude intracaval extension (occurring in 4% of patients)