NBL

Question 1

NBL epidemiology

Answer 1

Median age 18 months
Make predominance
AA and native Americans more likely to have poor outcomes and poor prognostic features

Question 2

Cytogenetic abnormalities

Answer 2

Familial neuroblastomas

PHOX2B germline mutation ( hypoventilation, hirshorungs)
Anaplastic lymphoma kinase ALK germline mutation

Somatic mutations

Chromosomal gains or losses
- MYCN amplification 20% ( > 10 gene copies) 
-ALK aberrations, amplification 
2-3 % 
-17q gain detected 60% 

-segmental chromosomal and diploid
-1p36 ( 20-3% tumors)
Associated with MYCNA
Chromosome 11q23
20-30% tumors not associated with MYCNA
Chromosome 14q32
20-25% of tumors

Question 3

Somatic genetic mutations

Answer 3

ATRX ( alpha thal, dd, x-linked) common in adolescents

TERT telomerase reverse transcriptase

Question 4

Pathological features of NBL

Answer 4

SRBC tumors
Varying degree of neuronal differentiation
Homer- Wright rosette patters- tumor cells around neutrophils
- varying degree of Schwannian strong intermixed with tumor cells
-Varying degree of mitosis and karyorrhexis

Question 5

Classifications

Answer 5

international neuroblastoma pathology classification.

- unfavourable histology by NIPC have worse outcome

Question 6

Laboratory findings of NBL

Answer 6

HVA and VMA elevation

NSE, LDH AND FERRITIN ELEVATION

Question 7

OMA

VIPoma

Answer 7

Occurs 4% children with NBL
Myoclonus jerks and random eye movements with cerebellar ataxia
Associated with favorable features
Long term neurological deficits

Kerner-Morrison syndrome

• Tumor secretes vasoactive intestinal peptide
• Causes intractable secretory diarrhea

Question 8

What imaging modalities can be used to diagnose NBL

Answer 8

CT/MRI ( spine)
MIBG- to assess metastatic disease.
If not MIBG avid, can use PEt SCAN

Question 9

Staging systems

Answer 9

INSS- surgical system
1- localized tumor gross excision -/+ microscopic disease
2a- localized tumor incomplete resection- LN negative
2b- localized tumor incomplete resection- LN positive
3- unresectable unilateral tumor infiltrating midline w/wo regional LN
4- any primary tu or with dissemination to distant LN, bone, BM, liver, skin
4s- limited to skin, liver and or bone marrow

INRGSS
L1- localized tumor not involving vital structures as defined by the list of image- define risk factors and confined to one body compartment
L2- locoregional tumor with presence of one or more image defined risk factors
M- Distant metastatic disease
MS- kid<18 mo limited to liver, skin or BM

Question 10

Risk stratification

Answer 10

Low Risk
- INSS 1, 2 and 4, INRGSS L1
- any age
- no MYC NA
Intermediate risk
- INSS 3 or INRGSS L2
- INSS 4, INRGSSM AND age <18 months
- No- MYCNA
High Risk
-MYCN
INSS stage 4, INRGSS M and age >18 months with UHN OR unfavourable genomics

Question 11

Treatment

Answer 11

Low Risk

• EFS/OS > 90%
• resection without damage of organs
• complete resection not mandatory as they mature.
• chemotherapy not usually used.

Intermediate risk

• EFS/OS 85/90%
• Surgery- to achieve >50% reduction of primary tu or size; complete resection. It mandatory
• chemotherapy - multi agent 2-8 cycles
• radiation- reserved for acute life organ symptoms

High Risk therapy
Induction with chemotherapy
Consolidation with auto transplant and radiation.
Post consolidation. With immunotherapy and atra.

Question 12

Response assessment

Answer 12

International NBL RESPONSE CRITERIA
CR- no evidence of primary, or metastatic disease, normal HVA and VMA, MIBG neg

VGPR- reduction >90% of tumor, no mets and HVA/VMA normal

PR- 50-90% reduction of Tumor,, > 50% reduction of metastatic sites

Mixed response- >50 in one site and <50% in other site. No new lesions

No response - < 50% reduction in one site and less than 25% increase in any existing lesion

PD-new lesions or increase 25% any lesion