Ewings Tumour

Principles

 

Treatment algorithm similar to OS

 

Overall prognosis similar to OS

- 70% long term survival

 

Definition

 

A malignant neoplasm composed of small round cells of uncertain histogenesis

 

Genetics

 

Recent data suggests it is of neuroepithelial derivation

- ? neuroectodermal cells

- mesenchymal stem cell of neural crest origin

 

Translocation 

- T (11, 22) 

- balanced 

 

Ewing's tumour & PNET have a similar histogenesis

 

Location

 

Central 

- pelvis (12%)

- scapula

- vertebrae

- rib

- sacrum

 

Peripheral 

- femur (20%)

- humerus (11%)

- fibula

 

Epidemiology

 

Usually 2nd decade

- 5-30 years

- peak 10 years

 

M:F 3:2

 

History

 

Usually complain of pain & then swelling

 

± Systemic symptoms

- fever, weight loss, malaise

- poor prognosis

 

Examination

 

Usually large soft tissue mass

 

May have local signs

- tenderness

- erythema & induration

 

Xray 

 

Diffuse permeative destruction

 

Ewings Tumour AcromionEwings Tumour Proximal Femur

 

Extension into soft tissue

 

Periosteal reaction

- codman's triangle

- onion skinning

- sunburst appearance

 

DDx on x-ray

 

Ewing's

Osteomyelitis

EG

 

Blood Tests

 

Elevated ESR & LDH 

- poor prognosis

 

May have anaemia or leucocytosis

 

Lung CT 

 

Pulmonary metastasis (20% GIII)

 

MRI 

 

Shows intramedullary extent 

- extraosseous extent more difficult

- reactive oedema difficult to distinguish from tumour

 

MRI Ewings Sarcoma Proximal FemurMRI Ewings Tumour Proximal Femur

 

Bone Scan

 

Shows occult bone metastases

- 10% have multiple bone involvement at time of presentation

 

Ewings Bone Scan

 

Bone marrow aspirate

 

Important part of staging for Ewing's

 

Staging

 

Usually Grade IIB lesion 

- high grade & extracompartmental

 

20% Grade III

- pulmonary mets

 

In reality all have micrometastasis

 

Bone marrow aspirate and trephine

- at distant site 

- look for marrow spread

 

Histology

 

Sheets of uniform round cells / small round cell tumours

- cells have distinct nuclei with minimal cytoplasm

- indistinct cytoplasmic border

- mitotic activity seldom high

 

Areas of necrosis

- 'geographic necrosis'

- pseudorosettes of cells around central necrosis

 

DDx

 

Use histology, immunohistochemistry, EM and cytogenetics 

- Ewings

- PNET

- lymphoma

- rhabdomyosarcoma

- metastatic neuroblastoma

 

1.  Ewings

 

PAS reaction positive 90%

- stains glycogen and mucin

- other tumours can be positive i.e. neuroblastoma

 

Ewing / PNET

- positive to vimentin / S100 / MIC 2

- MIC 2 specific for neuroectodermal tumours 

 

Cytogenetics

- 11:22 translocation in all  PNET 

 

2.  PNET (Primitive Neuroectodermal Tumour)

 

Variant of Ewing's

 

Composed of

- adult neuroblastoma

- Ewing-like tumour

- Askin tumour - thoracopulmonary PNET

 

Separate group because older age group with worse prognosis

 

3.  Lymphoma of bone 

 

Most important

- older age

- more bone formation

- "common leukocyte antigen" positive

 

4.  Rhabdomyosarcoma

 

Actin / desmin / myoglobin positive

 

EM

- cytoplasmic filaments

- occasional Z bodies

- prominent IC glycogen storage deposits

 

5.  Metastatic neuroblastoma

- PAS positive

- negative to vimentin, MIC 2

 

Other

- small cell OS

- mesenchymal cell chondrosarcoma

- osteomyelitis 

- Eosinophilic Granuloma

 

Management

 

Historically

 

Irradiation only 

- poor results

- survival 25% at 5 years

- local recurrence 35%

- high complication rate (soft tissue damage / pathological fracture / premature closure of physes / 2° sarcoma)

 

Now

 

Chemotherapy is mainstay & primary treatment

- surgery / radiotherapy adjuvant treatment

- significantly more successful

- 60% survival at 5 years

- 40% if metastasis on diagnosis

 

Algorithm

 

1. Neoadjuvent chemotherapy

 

2. Restage

 

3. Surgical resection

- if can get adequate margins

 

4. Chemotherapy

 

5.  Radiotherapy

- if margins inadequate

 

1.  Neoadjuvant Multidrug Chemotherapy

 

Usually dramatically shrinks tumour

- entire soft tissue component can resolve

- period controversial

- principle is to treat to maximum response

 

Pre - chemothearpy

- LFT's / Renal function / Cardiac echo or Thallium scan prior to intensive chemotherapy

- preserve sperm / ovum

 

VAAC Regime

- Vincristine

- Actinomycin

- Adriamycin

- Cisplatin

 

Alternate with

- Iphosphamide

- VP 16 = Etoposide

 

2.  Restage radiographically

 

See response following neoadjuvent chemotherapy

- MRI of affected region

- CT Chest

 

3. Wide Resection ± DXRT of residual tumour

 

Excision best if possible

- amputate if limb salvage not possible

- irradiation if resection not feasible

- resect bone to pre-chemo margin 

- resect ST to post-chemo margin

 

Assess histological response

- > 95% necrosis

 

Surgery improves survival

- removes remaining cancer cells

- removes chemo resistant cells 

 

4. Adjuvant Chemotherapy

 

Continue neoadjuvant regimen

- total chemotherapy is usually 18/12

 

Prognosis

 

1.  Site

- hands and feet better than pelvis and central

 

2.  Size

- > 8-10 cm do worse

- > 100 ml on CT

 

3.  Metastasis at diagnosis

 

4.  Response to chemotherapy

- > 95% necrosis

 

5.  Surgery

- improves survival if resectable

 

Survival

 

No metastasis at diagnosis

- 60% 5 year

 

Metastasis at diagnosis

- 40% 5 year

 

Local recurrence

- 5% local recurrence with surgery

- 25% without

 

Radiotherapy

 

Indications

- incomplete surgical margins

- unresectable

 

If need to use RTX, should use prosthesis rather than allograft

 

Complications

- physeal arrest

- joint contractures

- muscle atrophy

- pathological fracture

 

Secondary malignancy / sarcoma

- increased with young age

- 40x increase if >60 Gy

- strong cumulative risk at 10 years of 35% secondary malignancy