Ewing Sarcoma

 

Ewings femurCT EwingsMRI Ewings

 

Definition

 

A highly malignant tumor composed of small round cells

 

Second most common bone malignancy in childhood and adolescence

 

Genetics

 

Likely of neurogenic origin

Balanced translocation t11;22

 

Location

 

Central 

- pelvis (12%)

- scapula / vertebrae / rib / sacrum

 

Peripheral 

- femur (20%) / humerus (11%) / fibula

 

Epidemiology

 

Usually 2nd decade

- 5-30 years

- peak 10 years

 

Male:Female 3:2

 

History

 

Pain and swelling

 

± Systemic symptoms

- fever, weight loss, malaise

 

Examination

 

Usually large soft tissue mass

 

Bloods

 

Elevated WCC, ESR

Elevated LDH associated with poorer prognosis

 

Xray 

 

Often diaphyseal

- diffuse permeative destruction

- can be subtle

 

Periosteal reaction

- Codman's triangle / onion skinning / sunburst appearance

 

Ewings femur

Sunburst appearance

 

Ewings distal femur

Onion skinning lateral distal femur

 

Ewings Tumour AcromionEwings Tumour Proximal Femur

Ewing's acomion                                    Ewings lesser trochanter

 

Ewings humerus 1Ewings humerus 2

Subtle periosteal reaction humerus

 

Pelvis Ewings 2Pelvis Ewings 1

Ewings superior pubic rami

 

Differential diagnosis

 

Ewing's / lymphoma / osteomyelitis / eosinophilic granuloma

 

MRI 

 

Low signal intensity of T1 / high signal intensity on T2

- intramedullary extent

- skip lesions

 

Significant soft tissue mass with significant edema

 

Ewings skip lesion

Pathological fracture with skip lesion

 

MRI Ewings Sarcoma Proximal FemurMRI Ewings Tumour Proximal Femur

Ewing proximal femur

 

Ewings humerus 1Ewings humerus MRI

Ewing's humerus

 

Ewings midshaft femurEwings femur diaphysis MRIEwings femoral diaphysis MRI 2

Ewing's femoral diaphysis, subtle on xray with large soft tissue component

 

Ewings MRI femur 1Ewings MRI femur 2Ewings femur MRI axial

Ewing's distal femur

 

Ewings pelvisEwings pelvis MRI

Ewings iliac crest

 

CT

 

Ewings femurCT Ewings

 

Bone Scan

 

Look fo occult bone metastases

 

Ewings Bone Scan

Ewings proximal femur involving femoral head

 

Chest Xray

 

Ewings chest mets

Chest metastasis

 

Histology

 

Ewings histol 1Ewings histol 2Ewings histol 3

 

Sheets of uniform round cells

- distinct nuclei with minimal cytoplasm

- abundant glycogen

- positivity for neural markers such as S-100 protein / vimentin

 

Rosette formation

- indicative of neural differentiation

 

Differential diagnosis histology of small round cell tumors

- histology / immunohistochemistry / electron microscope / cytogenetics 

 

DIfferential Diagnosis   Immunohistochemisty   Electron microsope Cytogenics
Ewings  

PAS reaction positive 90%

- stains glycogen and mucin

Positive to vimentin / S100 / MIC 2    

EWS-FLI1 fusion gene t(11;22) translocation

PNET (Primitive Neuroectodermal Tumour)

 

Older population

Worse prognosis

  Positive to vimentin / S100 / MIC 2  

t11;22 translocation

Lymphoma   Common leukocyte antigen      
Rhabdomyosarcoma   Actin / desmin / myoglobin positive  

Cytoplasmic filaments

Occasional Z bodies

 
Metastatic neuroblastoma   PAS reaction positive Negative to vimentin, MIC 2    

 

Cytogenics

 

EWS-FLI1 fusion gene from t(11;22) translocation seen in 85% of Ewing's

 

Le Deley et al J Clin Oncol 2010

- European Ewing study group

- 565 patients

- studied different types of fusion genes

- no difference in prognosis or outcomes

 

Bone marrow biopsy

 

Cesari et al Paediatr Blood Cancer 2019

- 504 cases of Ewing's

- incidence of positive Ewing's on biopsy was 2%

- of these 11/12 had known metastasis on imaging

- suggest reconsidering bone marrow biopsy as part of staging for Ewing's

 

Management

 

Algorithm

 

1. Neoadjuvent chemotherapy

2. Restage

3. Surgical resection

4. Chemotherapy

5. Radiotherapy - if margins inadequate

 

Preoperative Chemotherapy

 

Aim

- eradicate micrometasis

- reduce tumor volume for resection

- guide postoperative chemotherapy

 

VACD Regime (Vincristine / Actinomycin / Cisplatin / Doxorubicin)

 

Alternate with Iphosphamide / Etoposide

 

Restage

 

See response following neoadjuvent chemotherapy

- MRI of affected region

- CT Chest

 

Wide Resection - limb salvage / amputation

 

2 cm margin of normal tissue if able

Assess histological response

 

Ewings pelvisEwings pelvis surgical resection

 

Pelvis wide resection

 

Ewings MRI femur 1Ewings femur resection 1Ewings femur resection 2

 

Ewings path 4Ewings path 3Ewings path 2Ewing path 1

 

Ewings femurEwings resection 1Ewings femur post op

 

Radiotherapy

 

Indications

- inadequate margins

- non resectable

- poor response to chemotherapy

 

Prognosis

 

1.  Location

 

Lower survival with central Ewing's

 

Brown et al Cancer Treat Res Comm 2022

- 296 / 1152 (26%) patients with Ewing sarcoma of the pelvic bones

- metastasis in 46% at time of diagnosis

- only 29% received surgical resection

- 5 year survival 40%

- 10 year 42%

- higher metastasis and lower survival compared to non pelvic Ewing's

 

Andreou et al CORR 2020

- 339 pelvic Ewing's

- 47% had metastasis at time of diagnosis

- 180 patients localized disease evaluated

- sacral tumors 5 year survival 72%

- innominate bone tumors 5 year survival 56%

 

2.  Disease volume

 

Paulussen et al J Clin Oncol 2008

- 647 patients randomized to chemotherapy based upon tumor volume

- < 100 mls versus > 100 mls

- < 100 mls 5 year survival 68%

- > 100 mls 5 year survival 52%

 

3.  Metastasis

 

Ladenstein et al J Clin Oncol 2010

- 281 patients with disseminated Ewings

- treated with chemotherapy / surgery / chemotherapy / stem cell transplant

- 3 year disease free survival 27%

 

4.  Response to chemotherapy

 

Albergo et al Bone Joint J 2016

- 293 patients without metastasis

- survival based on guide to chemotherapy

- 0 - 50% necrosis: 5 year survival 49%

- 51 - 99% necrosis: 5 year survival 72%

- 100% necrosis: 5 year survival 94%

 

5.  Resectable disease

 

Zeng et al Cancer Med 2023

- 143 patients average age 10 with localized Ewing's

- 5 year survival 77%

- higher with resectable disease