Neuroblastoma

Question 1

What are cancer stem cells?

Name a specific marker

Answer 1

Subpopulation of cells within a tumor with the ability to self-renew, generate differentiated progeny and create heterogenous cancer population, with increased resistance to chemo and propensity to metastatize
CD133+

Question 2

Genetic disorders associated with NBL (6)

Answer 2

Turner syndrome
Noonan (PTPN11 mutations)
Neuro-cardio-facial syndrome, e.g. Costello syndrome
NF1
Beckwith-Weidemann syndrome
Simpson-Golabi-Behmel syndrome type 1

Question 3

Germline mutations associated with hereditary NBL

Answer 3

PHOX2B (chr 4)

ALK

Question 4

What is associated with heterozygous PHOX2B mutation?

Answer 4

Neuroblastoma, ganglioneuroblastoma, congenital central hypoventilation syndrome, Hisrchprung disease

Question 5

Genetic aberrations seen in sporadic NBL? (4)

Answer 5

DNA ploidy
MYCN amplification
ALK amplification or mutation
ATRX mutation

Question 6

Chromosomal anomalies seen in sporadic NBL? (6)

Answer 6

Chromotripsis
Chr 1p LOH
Chr 11q LOH
Chr 14q LOH
Chr 17q gain
LIN28B overexpression

Question 7

VIP tumor secretion:

• What are the symptoms?
• What is the treatment?
• What is the prognosis?

Answer 7

Chronic watery diarrhea, failure to thrive
Surgical resection of primary tumor
Excellent

Question 8

What is the prognosis of Ospoclonus Myoclonus Ataxia syndrome?

Answer 8

70-80% with long-term neurological sequelae; immunosuppresive treatments useful fr acute symptoms but none associated with improved long-term outcome

Question 9

What is ROHHAD?

Answer 9

Syndrome including: Rapid-onset obesity, hypothalamic dysfunction, hypoventilation and automonic dysregulation;
Thought to be paraneoplasic (1/3 associated with neural crest tumors)
Poor prognosis, at least 25% mortality 2nd to respiratory insufficiency

Question 10

Urinary catecholamines:

• What is their sensitivity?
• Technique used

Answer 10

90-95%

HPLC

Question 11

MIBG scan:

- Sensitivity?

Answer 11

90-95%

Question 12

Bone scan:

- Role in NBL staging

Answer 12

Only recommended in cases in which primary tumor is not MIGB avid, or MIBG-avidity unknown (e.g. resected before MIBG)
Sensitive for bone mets but less specific

Question 13

List differences between INSS and INRG staging system?

Answer 13

1. INRG uses radiologic factors rather than resectability
2. INRG doesn’t include midline and LN status
3. INRG 4s includes a 18 months-old age cutoff and L2 tumors (INSS: 12 months, localized tumors)

Question 14

List elements included in the INRG classification?

Answer 14

• INRG stage
• Age
• Histology
• Tumor differenciation
• MYCN status
• 11q status
• Tumor ploidy

Question 15

Stage 4S disease: who should be treated?

Leading causes of deaths (3)

Answer 15

If evidence of worsening organ function, respiratory compromise, and/or significant hepatomegaly

• Respiratory insuffiiciency
• Hepatic dysfunction
• DIC

Question 16

Radiation therapy in HR NBL:

• Volume
• Dose

Answer 16

Volume: pre-surgical volume (post-induction chemo)
Dose: 1.260Gy

Question 17

What are the conclusions of the Quebec Neuroblastoma Screening Project?

Answer 17

Screening for neuroblastoma increases the incidence in infants without decreasing the incidence of unfavourable advanced-stage disease in older children. Does not reduce mortality