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Ewings Sarcoma

Ewing’s Sarcoma

Description

Ewing’s Sarcoma is a primary tumor of bone belonging to a primitive neuroectodermal lineage (PNETs).  Primary Neuroectodermal Tumor

Clinical Manifestations

Ewing’s Sarcoma often presents a painful limb with or without a soft tissue mass in an adolescent.  There are typically accompanying symptoms such as general malaise and fever.  Spinopelvic involvement can manifest as neurologic symptoms.

 

Clinical examination can find palpable soft tissue mass or nerve tension signs depending on the location of the lesion.

Red flags

Similar Lesions – The radiographic findings and associated symptoms (fever, malaise and elevated ESR or CRP) can be mistaken for acute hematogenous osteomyelitis in children.

 

Rib lesions – Ewing’s Sarcoma is the most common malignant rib tumor in childhood

Epidemiology

Ewing’s Sarcoma is a very rare bone tumor of childhood.  It is the second most common primary bone malignancy in this age group (second to osteosarcoma).  Ewing’s Sarcoma is more common in Caucasian populations than African American or Asian.  There is a slight male predilection.  Although a genetic mutation is diagnostic of the condition, it is most commonly a point mutation and sibling’s therefore carry only the risk of the general population.

 

The disease is most common the long bones of the appendicular skeleton and bones of the pelvis.  The fibula is a very common site for Ewing’s Sarcoma and a relatively rare site for other malignant tumors.

Pathology and pathophysiology

Grossly, there tumor are grey/white and may have areas of semi-liquid tumor.  The can be quite reminiscent of an infection if entered in surgery.

 

Histopathologies of specimens reveal sheets of monoclonal small round basophilic cells.  The nuclear/cytoplasm ratio is high and there are many immunohistochemical stains which are positive.  The most contemporary stains are CD99 (aka MIC2), and T/B cell specific stains (to differentiate from myeloproliferative lesions).  Cytogenetic analysis is the most specific expression of the tumor cells.  The chromosomal translocation t(11;22)(q23;q11) is the most commonwith about 85% of cases being positive.  The classic translocation produces a tumor gene product EWS/FLY1.  The majority of the less common translocations still produce a gene product containing EWS.

 

Patients with Ewing’s Sarcoma are at risk for disease progression which can be quite rapid both locally and distally.

Differential diagnosis

 

  Etiology

 The causative factor for the translocation is unknown.  The translocation gene product EWS-FLI1 induces expressionof embryonic stem cell genes OCT4, SOX2 and NANOG in pediatric mesenchymal stem cells.

Radiographic and laboratory findings

 Plain radiographs are apt to show an infiltrative mass with little matrix.  There is often cortical destruction with soft tissue mass and robust periosteal reaction visible on the radiograph.  The classic description of the periosteal reaction in Ewing’s Sarcoma is onion skin where the periosteum is lifted sequentially by the soft tissue mass expanding from the bone giving the laminated appearance.

 


MRI typically shows a soft tissue mass that is larger than the bone lesion.  The tumor can often involve the medullary canal well outside of the apparent boundary of the lesion on plain radiography.  Water sensitive sequences will often show extensive peritumoral edema in surrounding muscle and bone.

 

Bone marrow biopsy is part of the staging for Ewing’s Sarcoma and aside from having tumor cell present or not is usually unremarkable.

 

Chest CT scan is performed for staging purposes.   Aside from metastasis, there is no specific abnormality.

 

Serum ESR and CRP can be elevated.

Risk factors and prevention

 There are no identified risk factors for development of disease.  Central locations (spine and pelvis) are associated with worse outcomes.  Metastatic disease at presentation is associated with poor outcomes.

Treatment options

Chemotherapy is the mainstay of disease treatment particularly in cases presenting with metastasis.  Vincristine, Adriamycin and Cyclophosphamide (VAC) is a common regimen for the systemic treatment of the disease.  Treatment in neoadjuvant setting is the preferred method for treatment.  Following induction chemotherapy, surgery is performed for local disease control followed by completion of chemotherapy.  In cases where surgery is no done, radiotherapy is used to treat the tumor at the conclusion of chemotherapy.

 

The use of radiation versus surgery for local disease control has been often debated.  Current thoughts on the subject tend to favor surgery for lesion resectable with acceptable morbidity.  Radiation has adequate rates of local control when used with chemotherapy however, the lifetime implications of treatment doses places the patient at risk for secondary sarcoma later in life if cure is affected by therapy.

 

Outcomes

 
5 year survival rates approach 70%. Pelvic lesions have a dismal prognosis due largely to the delay in diagnosis.  Patient with pelvic disease are more likely to present with metastatic disease and unresectable tumors.  These patient’s 5 year survival rates are closer to 40%.  Pateints presenting with metastasis and pelvic lesions have a 5 year survival rate of <20%.

 

Survival of the disease places the patient at risk for secondary malignancy from the radiation or chemotherapy.  Radiation induced sarcomas can arise in the irradiated fields.  Chemotherapeutics put patients at risk primarily for hematogenous malignancies.

Holistic medicine

 All sarcoma patients should have access to multidisciplinary care including nutrition, physical therapy and mental health support.

Miscellany

 

James Ewing (1866--1943) first described the tumor, establishing that the disease was separate from lymphoma and other types of cancer known at that time. Askin tumor is a chest wall Ewing Sarcoma in an infant. 

Key terms

 
 Ewing, Ewing’s, Sarcoma, EWS/FLY1, 11:22, permeative, infiltrative, onion skin, small round blue cell, VAC,

Skills and competencies

 
 
 The senior medical student should be able to identify permeative destructive lesions on a plain radiograph.  The medical student should be familiar with the expected histological appearance of the tumor and the utility of the more common immunohistochemical and disease specific markers (translocations).

Content

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