Ewing Sarcoma / pnet
(Primitive Neuroectodermal Tumor)
Epidemiology and Etiology:
- Bimodal
- almost exclusively caucasian
Common Sites:
- Long-bones
- Deep-seated
- Trunk
- Lower limbs
- Association with nerve trunk occasionally
Gross Features:
Histologic features:
- Small round cell tumor
- Sheets, lobules, trabeculae
of uniform small, round cells, slightly larger than lymphocytes
- Scant cytoplasm, may appear clear (glycogen)
use PAS & PASD
- Nuclei 10-15 um
- Finely granular chromatin, speckled with
nucleoli
- Little stroma apart
from fibrous septae
- Homer-Wright rosettes (with a central fibrillary space) maybe
- Flexner-Wintersteiner
rosettes rarely
- Pseudorosettes
(variable) maybe
- Relatively few mitotic figures
- Frequently hemorrhage & necrosis
- Prominent capillary network
- Intracytoplasmic
glycogen
Immunophenotype:
Marker:
|
Sensitivity:
|
Specificity:
|
MIC2 (CD99)
(diffuse,
membranous)
|
Nearly all
|
Not very
specific
(lymphoblastic
lymphoma & DSRCT, membranous)
|
PAS & PASD
(glycogen) (dot cytoplasmic staining)
|
|
Not specific
|
Vimentin
|
100%
|
Not specific
|
FLI-1
|
Majority
|
Not very
specific
|
NSE
|
|
|
LEU-7
|
|
|
Synaptophysin
|
|
|
Neurofilament
|
|
|
Chromogranin
|
|
|
S-100
|
|
|
Molecular features:
- t(11;22)(q24;q12) in 80-90%
- EWSR1-FLI1 fusion gene
- EWSR1 is in TET family of genes with FUS and
TAF15
- FLI1 is a member of the ETS family
- 5 EWSR1 binds to 3 FLI1
- type 1 transcript:
- exon 7 of EWS to exon 6 of FLI1
- may be better prognosis
- type 2 transcript:
- exon 7 of EWS to exon 5 of FLI1
- other breakpoints (20%)
- additional karyotype abnormalities in 2/3 of
cases
- +8 (one or more) (33%)
- +12 (one or more) (20%)
- +2 (10%)
- +14 (10%)
- +18 (10%)
- +20 (10%) (maybe poor prognosis)
- der(16)t(1;16)(q11-21;q11-13) (10%)
- complex karyotype (>5 changes) maybe poor
prognosis
- > 50 chromosomes maybe poor prognosis
- EWSR1 (22q12) - ERG (21q22) fusion gene (10-15%)
- t(21;22)(q21;q12) rarely seen b/c they transcribe
in opposite directions requiring a complex mechanism
- t(7;22)(q22;q12) in < 1%
- t(17;22)(q12;q12)
- t(2;22)(q33;q12)
- t(1;22)(p36;q12)
- Rare other EWSR1 rearrangements
- Rare rearrangements involving other TET family
genes (FUS, TAF15)
- ?rare rearrangements involving other genes aside
from TET family and ETS family?
Other features:
- On EM: glycogen granules grouped around the
nucleus
- Some intermediate-type cell junctions
- True desmosomes usually not seen
- Neurosecretory granules maybe
- But more pleomorphic and larger than those in neuroblastoma
- Poor prognosis
- Important prognostic factors:
- Age (< 18 y favorable)
- Size (< 8 cm favorable)
- Site (extremity > pelvis)
- Stage
- Response to treatment is an important
prognostic factor (Huvos classification):
- Grade I no necrosis (30% 3-year survival)
- Grade IIA 1-10% necrosis (30% 3-year
survival)
- Grade IIB 11-90% necrosis (49% 3-year
survival)
- Grade III 91-99% necrosis (73% 3-year
survival)
- Grade IV 100% necrosis (100% 3-year
survival)
- Distance of tumour
from all margins is important to document
- Local recurrence
- Radiation is indicated if wide margins are not
adequate
- High grade by definition
References:
- Essentials of AP 2006
- WHO book 2002
- Heim & Mitelman. Cancer Cytogenetics,
3rd ed. (2009)