Neuroblastoma Flashcards
what is the origin of neuroblastoma?
embryonic tumour of the sympathetic nervous system, arises from neural crest
two predominant cell types in neuroblastoma
neuroblasts
schwann cells
what other conditions does neuroblastoma frequently co-exist with?
other conditions related to neural crest development/migration (ie, cardiac and urogenital anomalies)
three mutations associated with hereditary neuroblastoma
PHOX2B
ALK
CDKN1C
five syndromes associated with neuroblastoma
beckwith-wiedemann (WT2) neurofibromatosis type 1 (NF1) turners noonans (PTPN11) costello syndrome
incidence of familial neuroblastoma
1-2%
what are PHOX2B germline mutations associated with?
- ganglioneuroblastoma
- Hirschprungs
- congenital central hypoventilation syndrome
what is hyperdiploid NBL associated with
favourable outcome
whole chromosome gains
favourable biology
what is diploid NBL associated with
defined as a DNA index = 1 - associated with segmental chromosomal aberrations and myc-n amplification
what are common segmental chromosomal aberrations
LOH 1p36
LOH 11q
17q gain
LOH 14q
how common is myc-n amplification
occurs in 20-30% of neuroblastoma
definition of myc-n amplification
> 10 copy numbers per diploid cell
how common are ALK mutations in neuroblastoma
occurs in 7-10% of sporadic neuroblastomas
what is chromothripsis and how commonly does it occur?
local shredding of chromosomes with subsequent random reassembly of the fragments, occurs in 18% of high-stage nbl
what is the most common cytogenetic abnormality in neuroblastoma
17q gain (occurs in > 60%), associated with unfavourable prognosis, metastatic disease
pathologic feature which is pathognomonic for neuroblastoma
Homer-Wright pseudorosette
what are the three main histologic patterns in neuroblastoma?
- neuroblastoma
- ganglioneuroblastoma
- ganglioneuroma
what is the pathologic classification used for nbl?
Previously used Shimada, now use INPC (international neuroblastoma pathology committee)
what components are part of the INPC pathologic classification?
- amount of stroma
- MKI index
- degree of differentiation
(compared to age related norms)
name 5 immunohistochemical stains used in nbl
Neuron-specific enolase (NSE), GD2, synaptophysin, chromogranin A, neurofilament protein, tyrosine hydroxylase, CD57, CD56
what is the most common presentation of nbl?
abdominal mass (65%)
what is horner syndrome
miosis (pupil constriction), ptosis, anhidrosis
name three paraneoplastic syndromes associated with neuroblastoma
- VIP secretion
- opsoclonus-myoclonus ataxia syndrome (OMS)
- ROHHAD (rapid-onset obesity with hypothal dysfunction, hypovent, autonomic dysregulation)
work up for neuroblastoma
- imaging (staging)
- MIBG
- urine catecholamines
- tissue for pathology
- bilateral bma / bx
