Ewing sarcoma is a highly aggressive, small round blue cell tumour affecting primarily adolescents and young adults, often characterised by t(11;22)(q24;q12) translocation, typically presenting as a permeative, diaphyseal lesion with an associated soft tissue mass and onion skin periosteal reaction.
Description
Ewing sarcoma is a primary bone tumour that predominantly affects children and adolescents. It is the second most common malignant bone tumour in this age group, after osteosarcoma. It belongs to a family of tumours including peripheral primitive neuroectodermal tumours (PNET), which together form the Ewing sarcoma family of tumours (ESFT). The tumours are typically aggressive and rapidly growing.
Pathogenesis
Ewing sarcoma typically arises due to a translocation event between chromosome 11 and 12 t(11;22)(q24;q12), leading to a fusion gene EWSR1-FLI1. This translocation is found in the majority of Ewing sarcoma cases.
Epidemiology, Risk Factors & Associations
- Predominantly affects children and adolescents, peak incidence in the second decade of life.
- No known environmental risk factors, sporadic occurrence.
- Slight male predilection.
- More common in Caucasian populations, rare in those of African descent.
Clinical Features
- Localised bone pain and swelling are the most common symptoms.
- Systemic symptoms such as fever, weight loss, and malaise may be present due to the aggressive nature of the tumour.
- Neurological symptoms may occur with spinal involvement.
Complications
- Local invasion leading to pathological fractures
- Metastasis – haematogenous route, typically to bone, lung then liver.
- Long term sequelae of treatment including physical disabilities, secondary malignancies and psychosocial issues.
Pathological Features
Histopathological
- Composed of small, round, blue cells with scant cytoplasm.
- Homer-Wright pseudorosettes indicates neural differentiation. Typically arranged in sheets with a rosette pattern suggestive of neural differentiation.
- Glycogen may be found in the cytoplasm of the tumour cells.
Biochemical
- EWSR1-FLI1 fusion gene can be detected via PCR or FISH.
- Serum lactate dehydrogenase (LDH) levels often elevated and correlate with prognosis.
- Leukocytosis and elevated erythrocyte sedimentation rate.
Radiological Features
General Features
- Aggressive permeative bone lesion with soft tissue mass
- Predominantly diaphyseal (33 – 35%) or meta-diaphyseal (45 – 60%) lesion of long bones with lytic and sclerotic components.
- Flat bones (25%): ilium, scapula, chest wall
- Axial skeleton (5%): sacrum
- Characteristic onion skin periosteal reaction.
- No calcified tumour matrix is produced
- Thick reactive endosteal (i.e intra-osseous) bone formation may be seen (which may mimic osteosarcoma). No bone formation within the soft-tissue (extra-osseous) component.
- MRI of the entire involved bone is recommended due to the propensity for skip lesions.
- A whole body MRI or a PET-CT may be used for initial staging to assess for distant metastasis.
XR
- A large soft tissue mass often associated with cortical destruction
- Wide zone of transition, no sclerotic margin
- Onion skin appearance due to layered periosteal reaction. May show sunburst pattern.
- Cortical saucerisation where the outer cortex appears depressed or scalloped over a long segment, due to remodelling from subperiosteal tumour
CT
- Better delineates cortical destruction and soft tissue extension.
- Periosteal reaction more clearly visualised.
- Chest: Assess for pulmonary metastases
MRI
- Modality of choice to evaluate the full extent of the tumour and any soft tissue involvement.
- T1: The tumour usually appears isointense to muscle and hypointense to fat.
- T2: The tumour is hyperintense. Areas of haemorrhage or necrosis within the tumour may demonstrate high signal intensity.
- T1 C+: The tumour demonstrates heterogeneous enhancement post-contrast administration, which can help delineate the extent of the lesion.
- STIR: Tumour shows high signal intensity.
- DWI: The tumour may demonstrate restricted diffusion.
PET
- PET-CT can be used for staging and response assessment. Ewing sarcoma typically shows high FDG uptake.
Grading and Staging
Staging is based on the extent of local invasion, the presence of metastasis, and the size of the primary tumour.
Differential Diagnosis
- Osteosarcoma: older age group, metaphyseal location, sunburst periosteal reaction
- Neuroblastoma: younger age group, typically presents with abdominal mass
- Lymphoma: usually more systemic symptoms, lack of classic onion skin appearance
Management
- Management typically involves a multimodality approach, including neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy or radiation.
- Prognosis varies but is generally poor, especially in cases with metastatic disease at presentation.