Peripheral Neuroblastic Tumours
Epidemiology and
Etiology:
- Most
common solid extracranial malignancy in first 2
years
- 96%
occur in the first decade
- 3.5%
in the second decade
Common Sites:
- Adrenals
(40%)
- Sympathetic
ganglia:
- Abdominal
(25%)
- Thoracic
(15%)
- Cervical
- Pelvic
-
Gross features:
- Calcifications
frequently
- Neuroblastoma:
- 1-10cm
- Encapsulated
- Soft,
grey-tan mass
- Hemorrhagic
often
- Cystic
change maybe
- Ganglioneuroblastoma and ganglioneuroma:
- Firmer
- Tan-white
- Nodular
ganglioneuroblastoma has nodules of softer
maybe hemorrhagic tissue within the firm tan-white tissue
Histologic
features:
- One or
more of the following elements:
- Undifferentiated
neuroblasts
- Neuropil
- Differentiating
neuroblasts
- Ganglion
cells
- Mature
neuritic processes
- Schwann
cells
- Fibrous
tissue
- Classification
here is INPC which is modified Shimada classification (see reference)
- Neuroblastoma (schwannian
stroma-poor):
- Small
round blue cells
- Dark
nuclei
- Scant
cytoplasm
- Poorly-defined
cell borders
- Solid
sheets of cells
- Neuropil (faint eosinophilic fibrillary
material) in background
- Homer-Wright
pseudorosettes (neuropil
in the middle) maybe
- Lacking
prominent Schwannian stroma
(Schwannian stroma-poor)
- May
rarely have microscopic, irregular foci of ganglioneuromatous
component
- May have
differentiating neuroblasts and abundant neuropil
- Definitive
prominent nucleolus
- Cytoplasm
expanded so that size of cell is 2x size of nucleus
- Necrosis,
hemorrhage, calcifications common
- Undifferentiated
subtype:
- No neuropil or differentiation
- Requires
supplementary techniques (ex. Immune)
- Pleomorphic subtype of
undifferentiated subtype:
- Large
with pleomorphic nuclei
- Prominent
nucleoli
- Moderate
to abundant cytoplasm
- Rhabdoid features maybe
- Poorly-differentiated
subtype:
- Neuropil background evident
- <
5% of cells show differentiation
- Readily
recognizable neuropil in background
- Differentiating
subtype:
- >=
5% of cells show differentiation
- Ganglioneuroblastoma (schwannian
stroma-rich):
- Foci
of neuroblastic elements in an expanding Schwannian stroma
comprising > 50% of tumour volume
- Atypical
variant of nodular ganglioneuroblastoma may
consist of neuroblastomatous elements with
only thin rim of ganglioneuromatous component
- Neuroblastic foci composed of a
mixture of neuroblastic cells with various
stages of differentiation
- Intermixed
subtype:
- Neuroblastic foci are not grossly
visible
- Nodular
subtype:
- Neuroblastic components are
grossly visible
- Signs
of differentiation:
- Ganglion
cells
- Schwannian stroma
- Ganglioneuroma (schwannian
stroma-dominant):
- Predominantly
Schwannian stroma
with only individually distributed neuronal elements
- No nesting
of neuroblastomatous elements (differentiating
neuroblasts, maturing and mature ganglion
cells)
- Maturing:
- Presence
of scattered foci of differentiating neuroblasts
along with fully mature ganglion cells
Immunophenotype:
Marker:
|
Sensitivity:
|
Specificity:
|
Neuron-specific
enolase
|
|
|
Chromogranin A
|
|
|
Synapophysin
|
|
|
NFP
|
|
|
Nestin
|
High
|
Not specific
|
TrkA (NGFR)
|
Favorable
prognostic
|
|
S100 (Schwann cells)
|
|
|
Tyrosine hydroxylase
|
|
Negative in
Ewing usually
|
Protein gene
product 9.5
|
|
|
GD2
|
|
|
NB84
|
|
|
CD99 (neg)
|
|
|
Desmin (neg)
|
|
|
LMWK (neg)
|
|
|
CD45 (neg)
|
|
|
Vimentin (neg)
|
Undifferentiated
may be positive
|
|
Molecular features:
- 17q
gain (unfavorable)
- 1p deletion
(unfavorable)
- 14q
deletion (unfavorable)
- 11q
deletion (unfavorable)
- N-myc amplification (2p) (unfavorable)
- DMs
and HSRs
- Myc-max protein complex in
the nucleus inhibits cellular differentiation and promotes proliferation
and apoptosis
- Usually
seen in undifferentiated and poorly-differentiated neuroblastomas
- Usually
correlates with high MKI
- Correlated
with 1p deletions, esp. del(1p36.3)
- Detected
by FISH or Southern
- May
rarely be seen in other SRCTs or leukemia
- DNA hyperdiploidy,
near triploidy (favorable if < 1y )
-
Staging:
- Stage
1:
- complete
gross excision (with or without microscopic residual)
- non-adherent
nodes are negative
- Stage
2A:
- Incomplete
gross resection
- Non-adherent
nodes are negative
- Stage
2B:
- Positive
ipsilateral nodes
- Negative
contralateral nodes
- Stage
3:
- Tumor
crosses the midline OR positive contralateral
nodes
- Stage
4S:
- Tumor
does not cross the midline
- Distant
mets limited to skin, liver, and/or bone
marrow (but not cortical bone; MIBG must be negative)
- Stage
4:
- Distant
spread beyond 4S.
Prognostic Indicators:
Variable:
|
Favorable:
|
Unfavorable:
|
Stage
|
1, 2, 4S
|
3, 4
|
Age
|
<= 1.5 year
|
> 5 year
|
Histology
|
Differentiation
Low MK index
(<=100/5000)
Calcification
present
|
No
differentiation
High MK index
(>200/5000)
Calcification
absent
|
DNA ploidy
|
Hyperdiploid
Near-triploid
|
Diploid or
near-diploid
Near-tetraploid
|
N-myc
|
Not amplified
|
Amplified
(ratio of N-myc to centromere of 2 averages
at least 10)
|
17q gain
|
Absent
|
Present
|
1p loss
|
Absent
|
Present
|
Trk-A expression
(NGFR)
|
Present
|
Absent
|
Telomerase
expression
|
Low/absent
|
Highly
expressed
|
MRP expression
|
Absent
|
Present
|
CD44 expression
|
Present
|
Absent
|
Serum markers:
Ferritin
LDH
|
Normal
<=1500 U/mL
|
Elevated
>1500 U/mL
|
IPMN
favorable/unfavorable histology (see table in reference)
|
|
|
Molecular features:
Other features:
- EM:
- Neurosecretory granules (dense core
granules of neurosecretory type)
- Neuritic processes with
microtubules
- Clinical
features:
- Abdominal
mass
- Spinal
cord compression
- Horner’s
syndrome
- Diarrhea
(VIP)
- Proptosis (orbital mass)
- Cutaneous nodules
- Ondine’s cures (impairment of
autonomic control of respiration)
- Opsoclonus-myoclonus syndrome (eye
movements) (cross-reactive antibodies to cerebellum)
- Elevation
of urinary catecholamines
- MIBG
scan positive (85%)
- Serum:
- LDH
(worse prognosis with high levels)
- NSE
(worse prognosis with high levels)
- Ferritin (worse prognosis when
elevated)
References:
- Robbins
& Cotran Pathologic Basis of Disease (2005)
- WHO
Pathology and Genetics of Tumours of the Nervous
System (2000)
- Joshi
VV. Peripheral neuroblastic tumors: pathologic
classification based on recommendations of international neuroblastoma pathology committee (Modification of shimada classification). Pediatr Dev Pathol. 3(2):184-99.