Extraskeletal Ewing Sarcoma

RAWA MUHSIN
 Definition

Malignant small round blue cell neoplasm of bone

and soft tissue characterized by specific EWSR1
mutations
ES and PNET represent continuous morphologic
spectrum
 Evidence of neuronal differentiation in PNET
Origin from mesenchymal stem cell or neural crest
stem cell
 Epidemiology

Rare
2nd decade of life
M:F ratio = 1.4:1.0
More common in Caucasians
 Clinical

Symptoms
 Swelling, pain, constitutional
Treatment
 Chemotherapy followed by surgery ± radiation
Prognosis
 Early metastasis to lungs, bone
 10-year survival: 67% (localized), 28% (metastasis)
 Poor with metastasis, axial, size >10 cm, age >19 years
 Gross

Tan to gray, friable cut surfaces

Hemorrhage and necrosis common
May display cystic change with necrotic, semiliquid
contents
Imaging
 Architecture

Sheets (densely packed)

Homer-Wright rosettes in PNET
Minimal intercellular collagen or reticulin
Rare myxoid change with microcyst formation
Necrosis with perivascular preservation of cells
 Cells

Uniform cells
 Rarely spindled
Scant cytoplasm with indistinct membranes
 Clear from glycogen
Fine chromatin, inconspicuous nucleoli
Atypical (large cell) variant
 Large nuclei, conspicuous nucleoli, pleomorphism, spindling
 Histochemistry

PAS +ve
 intracytoplasmic glycogen in up to 75% of tumors
Reticulin -ve
 Minimal or intercellular reticulin
 vs lymphoma (cells), synovial sarcoma (small cell groups)
 Immunohistochemistry

Antibody Pattern Positive Cases

CD99 Membrane 93% 1810
NKX2.2 Nucleus 84% 417
FLI-1 Nucleus 84% 685

HDGF (100% in 108 cases), caveolin-1 (96% in 385 cases), GSK-3-beta (89% in
372 cases), SLUG (84% in 369 cases), etc.
 Immunohistochemistry

Antibody Pattern Positive Cases

AE1/AE3 Cytoplasm 22% 655
CK-PAN Cytoplasm 9% 198
CAM 5.2 Cytoplasm 11% 307
34bE12 Cytoplasm 4% 284
EMA Cytoplasm 10% 98
CK7 Cytoplasm 0% 78
CK20 Cytoplasm 0% 40
CK19 Cytoplasm 10% 40
 Immunohistochemistry

Antibody Pattern Positive Cases

NSE Cytoplasm 50% 411
Synaptophysin Cytoplasm 36% 326
CD56 Membrane 25% 134
Chromogranin-A Cytoplasm 2% 265
 Molecular

Gene rearrangements of FET family gene with ETS

family gene
 FET gene family: EWSR1, FUS, TAF15
 ETS gene family: FLI1, ERG, ETV1, ETV4, FEV
 Molecular

EWSR1-FLI1 fusion
 t(11;22)(q24;q12)
 90%
EWSR1-ERG fusion
 t(21;22)(q12;q12)
 5-10%
EWSR1 variant translocations
 ETS and non-ETS
 <1%
 Differential diagnosis

Alveolar rhabdomyosarcoma
Synovial sarcoma
DSRCT
Lymphoma
CIC-DUX4 undifferentiated sarcoma
BCOR-CCNB3 fusion sarcoma
Neuroblastoma
Small cell carcinoma