Neuroblastoma

Question 1

Cellular origin and resulting anatomical sites?

Answer 1

Derived from neural crest cells the migrate to form the peripheral sympathetic nervous system.

Tumors arise anywhere along the sympathetic ganglia.

Question 2

INRG staging for Neuroblastoma:

Answer 2

L1 - Localized tumors with no IDRFs
L2 - Loco-regional tumors with one or more IDRF or contiguous body compartments.
M - metastatic disease
MS- less than 18 months, confined to marrow (less than 10% of marrow), liver and skin. Negative MIBG scan.

Question 3

Factors in risk stratification?

Answer 3

1) Age
2) Stage
3) MYCN status
4) histology (stroma rich or stroma poor)
5) LOH at 11q
6) DNA ploidy
7) Tumor differentiation

Question 4

Common sites of metastasis with NB?

Answer 4

Nodes
Bone marrow and cortex
Liver 
Skin
Orbits
Dura

Question 5

Urine and serum markers for NB?

Answer 5

VMA, HVA - urine

Neuron specific enolase, ferritin, and LDH for serum.

Question 6

Staging imaging?

Answer 6

• CT or MRI of primary compartment
• MIBG scan for Bony involvement
• CXR only for abdominal disease unless concerns for extension to the chest
• MIBG negative tumors can be imaged with PET
• Bone scan if MIBG negative tumors or primary already removed

Question 7

Survival with prenatal diagnosis of NB?

Answer 7

95%

Question 8

Imaging features of NB on fetal US?

Answer 8

1) Primarily solid lesions- usually small 2-4 cm, tend to grow
2) Cystic or homogenous masses - usually larger 3-10 cm, tend to remain stable in size or regress

Question 9

Postnatal workup for NB diagnosed on fetal US?

Answer 9

US followed by CT or MRI
CBC, LDH, urine catecholamines
MIBG if elevated catecholamines

Question 10

Postnatal surveillance protocol for antenatal NB?

Answer 10

US and urine HVA/VMA at week 3,6, 12, 18, 30, 42, 66, 90

CT at week 6, 42

If tumor or urine cats increases by 50% then resect.

Question 11

Criteria for NB observation w/o biopsy?

Answer 11

COG protocol ANBL1232

1) < 18 months
2) INRG L1
3) < 5 cm

Most tumors will shrink to a 1 cm or less mass. Safe to stop observing then (do not resect)

Question 12

Describe the various clinical presentation of NB

Answer 12

Signs and symptoms by metastasis site

Liver: Hepatomegaly on PE. abdominal compartment syndrome (MS)

skin: blueberry muffin (can use for Dx in MS - avoid laparotomy at all cost)

Bone: pain, #

Orbit: proptosis, racoon eye

Large thoracic tumor: dysphagia, SOB

Apical thoracic tumor: Horner syndrome : ptosis, anhydriose, miosis

Spinal nerve / root invasion: paraplegia, weakness

Bone marrow: anemia, fatigue

Paraneoplastic
VIP secreting tumor: watery diarrhea, dehydration

Opsoclonus-myoclonus ataxia syndrome: non-directional nystagmus, jerky movement, ataxia

Question 13

A posterior mediastinal mass is identified on an xray done for a suspected pneumonia in a 18 months old. What’s your differential?

Answer 13

1) Thoracic NB
2) Congenital lung lesion
3) Bronchogenic duplication cyst
4) esophageal duplication

Question 14

What is the differential of small round blue cells tumors of childhood?

Answer 14

Retinoblastoma
Hepatoblastoma
Nephroblastoma (willms)
Neuroblastoma
Ewing sarcoma
Rhabdomyosarcoma
Lymphoma

Question 15

What is the differential of neonatal adrenal mass on US?

Answer 15

1) adrenal hemorrhage
2) NB
3) subdiaphragmatic pulmonary sequestration

On US, fine calcification are highly suggestive of NB

Question 16

Specific IDRF are described for each body compartment. Name 4 IDRF which apply regardless of location

Answer 16

1) tumor extending into more than 1 compartment
2) involvement of > 1/3 depth of neural foramina on axial plane
3) any neuro symptoms due to tumor involvement of spinal nerve or cord
4) contiguous organ infiltration with no visible plane on imaging

Ascites / pleural effusion, whether malignant or not, are not an IDRF. If a malignant pleural effusion is identified in another compartment, it represent an INRG stage M

Question 17

What are the histologic characteristics differentiating neuroblastoma (differentiated vs undifferentiated), ganglioneuroblastoma, and ganglioneuroma?

Answer 17

Neuroblastoma:
Schwanian stroma poor (< 50%) tumors.

The % of differentiating neuroblasts (cells maturing from neuroblast to ganglion) explains if tumor is classified as differentiated or undifferentiated.

Differentiated: small round blue cells (primitive cells) against a neuropil background. > 5% of differentiated neuroblast

Undifferentiated: no neuropil background. therefore IHC needed to make the diagnosis.

Ganglioneuroblastoma:
Schwanian rich stroma (>50%). presence of neuroblasts nested in neuropil.

Ganglioneuroma: schwannian stroma dominan in which matury ganglion cells are evenly distributed.

Final classification into risk category requires MYNC, ploidy, 10q, mitotic index.

Question 18

To which patient can we offer upfront surgical resection, ie w/o neoadjuvant chemo

Answer 18

If you believe you can resect and respect the following:

• Total resection of primary tumor + nodes w/o removal or damage to adjacent structures
• Avoid intraoperative surgical complication which would delay chemotherapy

Then, you can consider removing L1/L2 depending on personal preference and experience

Question 19

Broadly speaking, what are the main elements of NB treatment (surgery/chemo/radiotherapy) for low / intermediate / high risk tumors?

Answer 19

Low risk: Surgical excision of the tumor is curative. No chemo, no radiotherapy

Intermediate: surgery and chemo

High risk: induction chemo, surgery, radio, consolidation/myelo ablation , maintenance