Synonyms

• Ewing's sarcoma
• PNET (historical)

Category

Bone and soft tissue

Behaviour

Malignant

Grade

High

Gender

Male (1.5:1)

Epidemiology

• Second most common primary Bone malignancy in children/adolescents
• Peak incidence 10-20 years

Clinical Features

• Pain and swelling, often mimicking infection
• Fever, elevated ESR, leukocytosis (pseudo-infection)
• May present with pathological fracture
• Systemic symptoms in metastatic disease

Location

• Diaphysis of long Bones
• Femur, tibia, humerus most common
• Flat Bones: pelvis, ribs, scapula
• Can occur in soft tissue (extraosseous Ewing)

Imaging

• Permeative Bone destruction
• Onion-skin periosteal reaction (layered)
• Large soft tissue mass (often disproportionate to Bone lesion)
• MRI: homogeneous T2 hyperintense soft tissue component

Pathology

• Small round blue cell tumour
• Sheets of uniform small cells with round nuclei
• PAS-positive (glycogen)
• Strong membranous CD99 expression
• NKX2-2 nuclear positivity

Genetics

• EWSR1-FLI1 fusion t(11;22)(q24;q12) in 85%
• EWSR1-ERG fusion t(21;22) in 10%
• Fusion-positive small round cell sarcoma classification
• Molecular confirmation required for diagnosis

Treatment

• Neoadjuvant chemotherapy (VDC/IE protocol)
• Local control: surgery and/or radiotherapy
• Adjuvant chemotherapy
• Radiotherapy if margins positive or unresectable

Prognosis

• 5-year survival 70% for localised disease
• Metastatic disease at presentation 25%: survival 20-30%
• Pelvic tumours have worse prognosis
• Histological response to chemotherapy is prognostic

Key Points

• Small round blue cell tumour of Bone in a child/adolescent
• EWSR1-FLI1 fusion is pathognomonic
• Onion-skin periosteal reaction on XR
• Multimodal treatment: chemo + surgery ± radiotherapy

Workup - Blood Tests

• FBC, U&E, LFTs, Bone profile - baseline and pre-chemotherapy
• LDH - prognostic marker; elevated indicates worse prognosis
• C-reactive protein, fibrinogen - if systemic inflammatory response

Workup - Local Imaging

• Plain radiograph
• MRI primary site with gadolinium - local staging; assess marrow and soft tissue extent, skip lesions

Workup - Biopsy

• Core needle biopsy at sarcoma centre - en bloc excision of tract
• EWSR1-ETS FISH (t(11;22)) or EWS-FLI1 RT-PCR - present in 90%; diagnostic
• Histology: small round blue cells with clear cytoplasm; High Ki67; extensive necrosis
• IHC: CD99+, FLI1+ (EWS fusion protein); SOX10, S100 Variable

Workup - Staging

• CT chest/abdomen/pelvis
• Whole-body MRI or PET-CT
• Bone marrow trephine - prognostic

Workup - Other

• Fertility counselling pre-chemotherapy
• MDT at Bone sarcoma specialist centre (NICE IOG) mandatory
• Risk stratification guides treatment intensity

Follow-up Summary

• Years 1–2: 3–4 monthly clinical review + CXR; MRI primary site at 3 months post local control then 6-monthly
• CT chest every 3 months for 2 years - lungs are the main metastatic site
• Bone scan or whole-body MRI at 6-monthly intervals for Bone metastasis surveillance in first 2 years
• Years 3–5: 6-monthly review + CXR; CT chest 6-monthly; Bone scan annually
• Years 6–10: Annual review + CXR; CT chest annually
• Paediatric patients: long-term monitoring for treatment-related late effects (cardiotoxicity, secondary malignancy)
• Discharge at 10 years with late effects Follow-up plan if applicable