[James Stephen Ewing (1866–1943), American pathologist, first professor of pathology at Cornell University]

Frequency: 3% of all pediatric cancers; 2^nd most common primary malignant bone tumor in children and adolescents after osteosarcoma; 4^th most common bone tumor after multiple myeloma, osteosarcoma, chondrosarcoma

Incidence: 200 cases / year in USA; 1–3÷1,000,000 children

Histo: crowded sheets of small round cells (10–15 µm), uniformly sized + solidly packed invading medullary cavity and entering subperiosteum via Haversian canals producing osteolysis, periostitis, soft-tissue mass; glycogen granules present (DDx to reticulum cell sarcoma); absence of alkaline phosphatase (DDx to osteosarcoma)

DDx small round cells:

• Ewing sarcoma, lymphoma, osteosarcoma, myeloma, neuroblastoma, embryonal rhabdomyosarcoma, eosinophilic granuloma

Immunohisto: positive for CD99 (MIC2, in 90%), vimentin, neuronspecific enolase, Leu7 (CD57), FL-1 protein

Peak age: 10–15 years (range, 5 months – 54 years); in 95% 4–25 years; in 30% <10 years; in 39% 11–15 years; in 31% >15 years; in 50% <20 years; M÷F = 1.5÷1; Caucasians in 96%, Blacks in 0.5–2%

• severe localized pain (82–88%); soft-tissue mass / swelling (60%)
• fever (20–49%), leukocytosis; anemia (in early metastases)
• ↑erythrocyte sedimentation rate (43%) simulating infection

Location:

• femur (21%), ilium (13%), tibia (11%), humerus (10%), fibula (8%), hand or foot (5%), radius or ulna (4%), clavicle (2%)
  1. long bones in 60%: metadiaphysis (44–59%), middiaphysis (33%), metaphysis (15%), metaepiphyseal (6%), epiphysis (2%); extension into epiphysis (in up to 10%)
  2. flat bones in 40%:, ribs (in 7% >age 10; in 30% <age 10), vertebrae (in 3–10%, lumbar >thoracic >cervical spine), pelvis, sacrum (6%), scapula (5%), calvaria (1%), mandible or maxilla (1%), facial bones (0.5%), sternum (0.2%)
     • >20 years of age predominantly in flat bones
     • <20 years of age predominantly in cylindrical bones (tumor derived from red marrow)

• 8–10 cm long aggressive lesion in shaft of long bone (62% lytic, 23% mixed density, 15% dense):
  • mottled “moth-eaten” to permeative destructive lesion (76–82%) with wide zone of transition in 96%
  • geographic bone destruction with wide zone of transition (= poor margination) in 15%
• penetration into soft tissue (56–80%) with preservation of tissue planes (DDx: osteomyelitis with diffuse soft-tissue swelling)
• early fusiform lamellated “onionskin” periosteal reaction (53–84%) / spiculated “sunburst” / “hair-on-end” (23%), Codman triangle
• cortical thickening (21%) + saucerization (6%)
• cortical destruction (19–42%) ± cortical sequestration
• reactive sclerotic new bone (32–40%) of dense cloudlike osteoid appearance
• pathologic fracture (15%)
• expansile bone remodeling (13%)

CT:

• density of soft-tissue component similar to muscle (98%):
  • commonly homogeneous
  • frequently asymmetrically circumferential
• linear channels of low attenuation extending through dense cortex ← tumor extension along neurovascular + haversian channels (66%)
• diffuse / peripheral nodular enhancement

MR (best modality):

• homogeneous (73%) intermediate SI (95%) on T1WI
• homogeneous (86%) low to intermediate (68%) SI on T2WI
• heterogeneously high signal commonly in larger lesions ← hemorrhage + necrosis
• marrow replacement (100%)
• cortical destruction (92%)
• associated asymmetrically circumferential soft-tissue mass (96%)
• visible connection between medullary canal + soft-tissue component (74%)
• diffuse / peripheral nodular enhancement

NUC:

• ↑uptake on bone scintigraphy (blood flow, blood pool, delayed imaging)
• ↑uptake on gallium scintigraphy

PET:

• ↑uptake of primary on PET with mean SUV of (a) 5.3 without metastases, (b) 11.3 with metastases
• depiction of osseous metastasis (37–88% sensitive)
• Ewing sarcoma of vertebra:
  • Prevalence: 3.5–15%
  • Mean age: 19 years; M÷F = 3÷2
  • Location: sacrum (55%), lumbar (25%), thoracic >cervical; >1 segment involved (8%)
  • Site:
    1. posterior elements (70%) with extension into vertebral body (86%)
    2. vertebral body (30%) with extension into posterior elements (83%)
  • large soft-tissue mass with invasion of spinal canal (91%)
  • disk spaces usually preserved
• Ewing sarcoma of rib:
  • primarily lytic / sclerotic / mixture of lysis + sclerosis
  • disproportionately large inhomogeneous soft-tissue mass
  • large intrathoracic + minimal extrathoracic component
  • may spread into spinal canal via intervertebral foramen

Metastases to: lung, bones, regional lymph nodes in 11–30% at time of diagnosis, in 40–45% within 2 years of diagnosis

Cx: pathologic fracture (5–14%)

Prognosis: 60–75% 5-year survival

DDx:

1. Multiple myeloma (older age group)
2. Osteomyelitis (duration of pain <2 weeks)
3. Eosinophilic granuloma (solid periosteal reaction)
4. Osteosarcoma (ossification in soft tissue, near age 20, no lamellar periosteal reaction)
5. Reticulum cell sarcoma (clinically healthy, between 30 and 50 years, no glycogen)
6. Neuroblastoma (<age 5)
7. Anaplastic metastatic carcinoma (>30 years of age)
8. Osteosarcoma
9. Hodgkin disease