Approach Considerations
No diagnostic blood studies provide pathognomonic or suggestive results to diagnose Ewing sarcoma. The most important factor that can help a patient with Ewing sarcoma is to be properly diagnosed and have a treatment plan established by an oncologist with significant experience in treating Ewing sarcoma.
Depending on the patient’s age and presenting symptoms, blood tests may be helpful in evaluating other diagnoses. Such tests may include blood cultures, measurement of C-reactive protein levels, a complete blood count (CBC), lactate dehydrogenase (LDH), and the erythrocyte sedimentation rate.
Cytogenetic and molecular studies
Cytogenetic studies should be used to confirm the diagnosis of Ewing sarcoma if t(11;22) or a related translocation is found. For standard cytogenetics, fresh tissue should be sent in appropriate media to a cytogenetic laboratory. In addition, a small piece of the tumor should be snap frozen in liquid nitrogen for molecular studies. [11]
Histology
Ewing sarcomas are small, round, blue cell tumors. They can be undifferentiated or differentiated, as reflected in rosette formation.
Immunohistochemical markers include membranous staining with MIC2 (12E7) antigen (CD99), which is characteristic but not pathognomonic. Muscle, lymphoid, and adrenergic markers should be negative.
Evaluation of the Primary Lesion and Metastases
Primary lesion
The priority is to obtain images of the suspected primary lesion or of any region with symptoms. If a bony mass is palpated, plain radiography is indicated. (See the image below.)
Radiograph of an 11-year-old boy with a large Ewing sarcoma in the right pelvic area. Destruction of the bone structure resulted from tumor involvement.
Magnetic resonance imaging (MRI) of the region can help in determining the extent of disease. MRI is immediately required if tumors are adjacent to critical neurologic structures, and emergency radiation therapy, surgery, and/or steroids should be considered to prevent nerve damage. Computed tomography (CT) scanning is helpful in delineating any bony involvement.
Metastases
Metastatic evaluation includes chest CT, radioisotopic bone scan, and bilateral bone marrow aspirate and biopsy. If the initial results indicate the probable existence of a tumor, chest CT scanning should be performed before surgical biopsy to avoid confusion of this finding with postoperative atelectasis.
Most centers now use whole-body MRI or fluorodeoxyglucose positron emission tomography (FDG-PET) scanning as sensitive tools to detect metastatic disease. Some studies suggest that FDG-PET [12, 13] may have superiority for detecting metastatic lesions over bone scanning; however, bone scanning may be useful to detect osseous metastases if Ewing sarcoma is sclerotic. [14]
Biopsy
If a lesion of Ewing sarcoma or another tumor is probable, consultation with a pediatric oncologist should be sought before a biopsy is performed. However, a biopsy specimen is required for definitive diagnosis.
The biopsy specimen should be evaluated by means of routine staining, as well as with immunohistochemical analysis with antibodies to differentiate the lesion from other small round blue cell tumors, such as rhabdomyosarcomas and lymphomas.
The biopsy should be performed after any potential therapy is fully considered, because all patients with Ewing sarcoma require some form of definitive local treatment.
Inappropriate biopsy or resection often increases patient morbidity or mortality. An example is a biopsy incision that extends outside the tumor resection at the time of definitive surgery. This causes the surgeon to excise additional tumor-contaminated tissue that might have been spared if proper planning occurred prior to a biopsy.
Staging
Staging includes local imaging to reveal the full extent of tumor prior to therapy, as well as evaluation of the patient for distant metastases.
Local imaging usually includes MRI and CT scanning. When bone is involved, these are complimentary techniques, but for soft-tissue lesions, MRI should be adequate in most cases.
The evaluation for metastases should include bilateral bone marrow biopsies (some centers obtain multiple cores on each side, but this is not well supported), chest CT scanning, and radionuclide total body scanning, such as technetium-99m (99m Tc) scanning. Many centers are now using FDG-PET scanning or total-body MRI to look for occult metastases. Although these techniques often produce false-positive results that require biopsy, some findings suggest that locating occult metastases and providing local therapy (radiation or surgery) improves survival.
A systematic review found that FDG-PET had a pooled 100% sensitivity and 96% specificity, a positive predictive value of 75%, and a negative predictive value of 100% for the detection of bone marrow metastasis, compared with bone marrow biopsy and aspiration. [15]
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Radiograph of an 11-year-old boy with a large Ewing sarcoma in the right pelvic area. Destruction of the bone structure resulted from tumor involvement.
