Overview

Question 1

What are the 4 most common malignancies of childhood?

Answer 1

4 most common malignancies of childhood:

1. Leukemia
2. Brain tumors
3. Lymphoma
4. NB

Question 2

What is the most common malignancy in infants?

Answer 2

NB is the most common malignancy in infants.

Question 3

Estimate the annual incidence of NB in the United States.

Answer 3

There are ∼650 cases/yr of NB in the United States.

Question 4

What is the median age at Dx for NB?

Answer 4

The median age at Dx is 17 mos, with a range b/t birth and 15 yrs.

Question 5

Name 5 syndromes associated with NB.

Answer 5

1. NF1
2. Hirschsprung Dz
3. Fetal hydantoin syndrome
4. Turner syndrome
5. Central hypoventilation syndrome

Question 6

What tests have been used to screen infants for NB?

Answer 6

Historically, infants were screened for NB using urinary catecholamines (vanillylmandelic acid/homovanillic acid).

Question 7

What % of NB pts have detectable urinary catecholamines?

Answer 7

90%

Question 8

Does screening improve survival in NB?

Answer 8

This is controversial. The value of catecholamine-based screening is limited by its FPR and b/c a high % of infant NBs spontaneously regress. The Quebec project increased the detection rate of NBs but failed to have an impact on mortality in the screened populations.

Question 9

What are the 3 types of neuroblastic tumors?

Answer 9

These tumors differ in the degree of cellular maturation.

1. NB (Schwannian stroma-poor)
2. Ganglioneuroblastoma (Schwannian stroma-rich)
3. Ganglioneuroma (Schwannian stroma-dominant)

Question 10

What markers distinguish NB from other small round blue tumors?

Answer 10

NB-specific markers:

1. NSE
2. Synaptophysin
3. Neurofilament

Question 11

What is the cell of origin for NB?

Answer 11

Neural crest cells of the sympathetic ganglion

Question 12

What are the classic histologic findings seen in NB?

Answer 12

Homer Wright pseudorosettes, hemorrhage, and calcification

Question 13

What genetic changes are associated with N-myc amplification?

Answer 13

Double-minute chromatin bodies and homogeneously staining regions are associated with N-myc amplification.

Question 14

What are the genetic/chromatin changes that portend a poor prognosis in NB?

Answer 14

1. N-myc amplification
2. LOH 1p or 11q
3. Trisomy 17q
4. diploid DNA
5. ↑ telomerase activity

Question 15

What germline mutations have been associated with a genetic predisposition to NB?

Answer 15

ALK gene mutation, PHOX2B gene mutation, and germline deletion of 1p36 or 11q14–23.

Question 16

In which pts does DNA content not have prognostic importance?

Answer 16

DNA content does not have prognostic importance in metastatic pts.

Question 17

What % of NB pts present with N-myc amplification?

Answer 17

30%–40% of pts present with N-myc amplification. An N-myc amplification is associated with poor prognosis.

Question 18

What % of NB pts present with 1p deletions?

Answer 18

20%–40% of pts present with 1p deletions.

Question 19

What is the genetic variation on 6p22 that is associated with clinically aggressive NB?

Answer 19

Homozygosity for 3 single nucleotide polymorphisms on 6p22 is associated with stage IV Dz, N-myc amplification, and Dz relapse. (Maris JM et al., NEJM 2008)

Question 20

What are some presenting Sx of NB?

Answer 20

Along with the presentation of a mass, NB may be associated with constitutional Sx (fever, malaise, pain, and weight loss), periorbital ecchymosis (“raccoon eyes”), “blueberry muffin” sign (nontender blue skin mets), scalp nodules, bone pain, irritable/ill appearance, diarrhea (↑ vasoactive intestinal peptide), Horner syndrome, opsomyoclonus truncal ataxia (rare paraneoplastic syndrome of ataxia, random eye movement, and myoclonic jerking associated with early stage but persists after cure), and Kerner–Morrison syndrome (diarrhea, low K).

Question 21

What are the most common sites of presentation for NB?

Answer 21

Adrenal medulla > paraspinal > post mediastinum

Question 22

In what age group is thoracic presentation of NB more common?

Answer 22

Thoracic NB is more common in infants.

Question 23

What % of NB pts present with mets overall? How does this differ by age?

Answer 23

75% of all NB pts present with mets overall. 60% of pts <1 yr present with localized Dz, while 70% of pts >1 yr present with mets.

Question 24

What are the most common sites of mets for NB?

Answer 24

NB metastasizes to bone (∼50%, commonly of the skull/orbit), LNs (35%), BM, liver, skin, and orbits. Lung mets are rare.

Question 25

What features distinguish NB from Wilms tumor?

Answer 25

Question 26

What is the most common pediatric extracranial malignancy?

What is the median age of diagnosis for this malignancy?

Answer 26

Neuroblastoma. There are approximately 650 cases of neuroblastoma per year in the United States. The median age at diagnosis is 22 months.

Goodman, MT, Gurney, JG, Smith,, et al. Sympathetic nervous system tumors. In: Ries, LAG, Smith, MA, Gurney, JG, et al., eds. Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975–1995. Bethesda, MD: National Cancer Institute; 1999. NIH Pub. No. 99-4649. SEER Program; 65-72.

Question 27

Where does neuroblastoma commonly present?

Answer 27

Neuroblastoma most commonly presents in the adrenal gland (35%), followed by the paraspinal ganglia in the thoracic, abdominal, or pelvic chains (30%), the posterior mediastinum (19%), and the cervical sympathetic ganglion (1%). Presenting symptoms may include a palpable abdominal mass, Horner’s syndrome, cord compression, respiratory compromise, and gastrointestinal disturbances.

Bernstein, ML, Leclerc, JM, Bunin, G, et al. A population-based study of neuroblastoma incidence, survival, and mortality in North America. J Clin Oncol. 1992;10:323-329.

Question 28

Which biologic features are unfavorable for neuroblastoma?

Answer 28

Amplification of N-myc protein (encoded by MYCN gene) correlates with advanced stage and poor prognosis and occurs in 30% to 40% of advanced stage neuroblastoma cases. DNA ploidy has shown to be predictive of both progression-free and overall survival, with children with hyperdiploid tumors having a better prognosis. Loss of heterozygosity of 1p and 11q are associated with a poor prognosis.

Attiyeh, EF, London, WB, Mosse, YP, et al. Chromosome 1p and 11 q deletions and outcome in neuroblastoma. N Engl J Med. 2005;53:2243-2253. doi:10.1056/NEJMoa052399.

Bowman, LC, Castleberry, RP, Cantor, A, et al. Genetic staging of unresectable or metastatic neuroblastoma in infants: a Pediatric Oncology Group Study. J Natl Cancer Inst. 1997;89:373-380. doi:10.1093/jnci/89.5.373.

Maris, JM. The biologic basis for neuroblastoma heterogeneity and risk stratification. Curr Opin Pediatric. 2005;17:7-13.