Bone Tumors
Ewing Sarcoma

James C. Wittig, MD
Sarcoma Surgeon/Orthopedic Oncologist
Ewing Sarcoma (PDF)

Ewing sarcoma is a small round blue cell sarcoma
It is a primary osseous neoplasm (cancer/sarcoma) composed of uniform, monotonous, small round blue cells without any matrix production
Fourth most common primary malignancy of bone
Approximately 5% of all biopsied tumors
Least differentiated of neuroectodermal neoplasms
Consistent presence of chromosomal abnormality
Occurs primarily in long bones
Most Ewing sarcoma cases (85%) are associated with a characteristic chromosomal translocation t(11;22)(q24;q12)  that results in EWS/FLI-1 chimeric protein

Signs/Symptoms:
Mass & localized pain.
Increased sedimentation rate, fever, anemia, malaise may occur and are usually indicative of metastatic disease
10% of patients present with multiple bony lesions
May have elevated LDH

Prevalence: Slight male predominance (1.5:1)
Uncommon in African Americans

Age: 80% cases occur in first two decades, median age is 13
10-25 years of age most common

Sites: Most commonly arises from diaphysis but can also arise from metadiaphysis and metaphysis;
Very rare epiphyseal involvement
Long Bones—Most common
Femur: Single most common site
Humerus
Flat Bones
Pelvis
Ribs

Permeative or moth eaten bone destruction
     Ill defined and malignant appearing
     Bony changes are often subtle
Soft Tissue Mass in 90% of of cases
Periosteal Reaction in 50% of cases
     Due to irritation, edema, tumor permeation
     Onion Skin (colic pattern of irritation)
     Hair on End  (rapid continuous lifting of periosteum)
Reactive Bone Sclerosis is rare but occurs in 10% of cases
No cartilage or bone production by tumor
Pathologic fracture in 10-15%
Ewing sarcoma rarely presents as a geographic, benign appearing tumor similar to a cyst or eosinophilic granuloma
There are rare cases of periosteal ewing sarcoma with no medullary involvement

X-ray: Ewing Sarcoma of Proximal Femur
(Top arrow)  Reactive Sclerosis
(Middle arrow)  Permeative Lesion
(Bottom arrow)  Onion Skin Periosteal Reaction

         Permeative Lesion
         Metadiaphysis
         Reactive Sclerosis
         Onion Skin Periosteal Reaction
         Skeletally Immature
         Soft Tissue Mass

MRI:  Ewing Sarcoma of Proximal Femur
Large Soft Tissue Mass and Extensive Marrow Involvement
(Arrows)  Large Soft Tissue Mass Best Visualized on MRI

X-ray/MRI: Ewing Sarcoma of Diaphysis of Femur
Tumor Barely Perceptible on X-Ray
MRI Demonstrates Marrow Involvement and Large Soft Tissue Mass

(Left arrow)  Permeative Bone Destruction
(Right arrow)  Soft Tissue Mass(

X-ray/MRI: Ewing Sarcoma of Diaphysis of Left Femur
(Top arrow)  Permeative Tumor
(Bottom arrow)  Soft Tissue Mass - No Mineralization

 
(Arrows)  Large Soft Tissue Mass

X-ray: Ewing Sarcoma of Right Femur

X-rays demonstrate a permeative lesion of the right proximal femur with slight sclerosis
The lesion is barely perceptible on the Xray
There is no periosteal reaction in this case


CT Scan: Ewing Sarcoma of Right Femur
This is a rare case where there is no soft tissue component

The CT scan demonstrates a permeative lesion through the proximal ½ of the femur
The cortex was mildly thickened and expanded (arrow)
There is no soft tissue component
There is no mineralization
10% of Ewing sarcoma’s do not have a soft tissue mass

CT Scan: Ewing Sarcoma of Right Femur
This is a rare case where there is no soft tissue component   
 (arrow)  Marrow Replacing Lesion


MRI T1 Weighted Image: Ewing Sarcoma of Right Proximal Femur
(Arrows) The T1 weighted MRI demonstrated a permeative lesion involving the upper ½ of the femur.
The bone was mildly expanded and the cortex slightly thickened
There was no Codman's triangle, hair on end or sunburst periosteal reaction
The MRI demonstrates fatty marrow replacement

MRI T2 Weighted Image: Ewing Sarcoma of Right Proximal Femur
The T2 weighted image demonstrates significant edema around the bone and lesion    (bright signal)
There was no soft tissue component associated with the tumor

MRI T1 Weighted Image: Ewing Sarcoma of Right Proximal Femur
(Arrow)  Hip Involvement

MRI T1 Weighted Axial Image: Ewing Sarcoma of Right Proximal Femur

X-ray: Ewing Sarcoma of Left Humerus Metadiaphysis
(Top Arrow) Soft Tissue Mass
(Bottom Arrow)  Permeative Lesion

              Permeative lesion left humeral shaft
              Pathological fracture (10% of cases)
              Soft tissue mass proximal humerus
              No mineralization
              Subtle "Hair on End" periosteal reaction

MRI T2: Ewing Sarcoma of Left Humerus
(Top left arrow)  Metadiaphyseal Origin
(Top Right arrow)  Large Soft Tissue Mass
(Bottom arrow)  Extensive Permeation of Marrow


Bone Scan: Ewing Sarcoma of Left Humerus demonstrates Intense Uptake

X-ray/CT Scan: Ewing Sarcoma of Right Proximal Humerus

X-ray/MRI of Ewing Sarcoma of Metadiaphysis of Distal Femur
(Arrow)  Permeative Lesion with Subtle Cortical Changes


   
(Arrow) Marrow Replacing Tumor

(Arrow) Larget Soft Tissue Mass Cortex Appears Intact

X-ray: Ewing Sarcoma of Scapula
There is subtle reactive sclerosis in the scapula neck and glenoid
The lesion is barely discernible on X-ray

(Arrow) Subtle Reactive Sclerosis



MRI: Ewing Sarcoma of Scapula
There is a large soft tissue component surrounding the scapula
(Arrow)  Long Soft Tissue Mass

X-ray: Ewing Sarcoma of Left Acetabulum and Superior Pubic Ramus
(Top arrow)  Permeative Lesions of Flat Bone
(Bottom arrow)  No Mineralization



MRI/CT Scan: Ewing Sarcoma of Left Acetabulum/Superior Pubic Ramus
(Arrows)  Soft Tissue Mass - No Mineralization

Intraosseous component
          Firm, grey-white, moist, and glistening
Extraosseous component
         Softer and more friable
Hemorrhagic and cystic degeneration may be present in either location
Diffuse involvement of the medullary cavity is often obvious

Gross Pathology: Ewing Sarcoma of Diaphysis of  Humerus
(Left arrow)    Extraosseous Soft Tissue Component
(Right arrow)  Diffuse Involvement of Medullary Canal of Diaphysis

Gross Pathology: Ewing Sarcoma of Metadiaphysis of Proximal Humerus
(Top arrow)  Permeative Marrow Lesion
(Bottom arrow)  Surrounding Soft Tissue Mass

Gross Pathology: Ewing Sarcoma of Fibula



Gross Pathology: Ewing Sarcoma of Distal Tibia Metaphysis



Gross Pathology: Ewing Sarcoma of Proximal Humerus Metadiaphysis

Microscopic Pathology: Ewing Sarcoma

          Small Round Blue Cells
          No Matrix
          Large Nuclei
          No Cytoplasm


Microscopic Pathology: Ewing Sarcoma

Microscopic Pathology: Ewing Sarcoma

         Uniform small round blue cells
         Few mitoses
         Large nucleui and virtually no cytoplasm
         No matrix
         Pink staining filaments


Microscopic Pathology: Ewing Sarcoma



Ewing Sarcoma: CD99 Stain Positive
Identifies MIC2 Overexpression




Ewing Sarcoma: PAS Positive
Glycogen Positivity

Ewing Sarcoma: Reticulin Poor


Ewing Sarcoma: Electron Microscope
Large nucleus with small nucleoli and fine granular chromatin
Minimal cytoplasm
Few cytoplasmic organelles
Glycogen granules in cytoplasm

Ewing sarcoma is one of  the most aggressive tumors
High propensity for
       Local recurrences
       Distant metastases (predominantly in lungs and other bones)
Noted for its lack of immunologic staining

Multiagent chemotherapy
          Most protocols administer preoperative chemotherapy then surgery is performed. Surgery is 
          followed by several courses of postoperative chemotherapy.
          Ewing sarcoma responds well to chemotherapy. Often there is a dramatic reduction in size 
          of the tumor.
          Most common chemotherapy agents utilized include as of 2008: Vincristine, Adriamycin, 
          Cyclophosphamide, Actinomycin-D, Ifosfamide, Etoposide
Surgical resection
           Limb sparing surgery whenever feasible unless there will be a large leg length discrepancy 
           that can not be accomodated for with surgery
           Rarely ever an amputation since Ewing sarcoma are sensitive to radiation
If surgical resection is not feasible, radiation may be utilized for local control (instead of an amputation) since Ewing sarcoma is highly sensitive to radiation, at least as per the author’s opinion. There may be some tumors that are selectively treated with radiation instead of surgery however most patients as of 2008 are treated with limb sparing surgery whenever feasible. Sometimes radiation is used in conjunction with surgery if a wide margin was not obtained at the time of surgery. The decision to administer radiation depends on size of tumor, site of tumor, response of tumor to preoperative chemotherapy and risks vs benefits of radiation.



Limb Sparing Surgery for Ewing Sarcoma of Proximal Femur



Sciatic Nerve Dissection and Mobilization
(Left arrow)  Hip Abductor Muscle
(Bottom arrow)  Sciatic Nerve
(Right arrow)  Ewing sarcoma

Hip External Rotators Released



Hip Capsule and Adductors Released; Femur Osteotomized

Defect
(Arrow)  Acetabulum

Prosthetic Reconstruction
Prosthesis Reduced into Acetabulum



X-ray: Upper Portion of Proximal Femur Tumor Prosthesis



Lower Portion of Proximal Femur Tumor Prosthesis
Prosthesis Cemented into Medullary Canal



Modular Segmental Proximal Femur Tumor Prosthesis



Ewing Sarcoma: Prosthetic Reconstruction of Proximal Humerus with Proximal Humerus Tumor Prosthesis Limb Sparing Surgery