What are the initial staging tests for newly diagnosed Ewing Sarcoma in a 12-year-old boy?

Initial Staging Tests for Newly Diagnosed Ewing Sarcoma in a 12-Year-Old Boy

Complete staging should be performed before biopsy and must include chest CT, contrast-enhanced MRI of the primary site, whole-body FDG-PET/CT (preferred over bone scan), and serum LDH, with bone marrow biopsy now optional given the high sensitivity of modern imaging. 1

Essential Imaging Studies

Chest Imaging

• CT chest with or without contrast is mandatory to detect pulmonary metastases, as lungs are among the most common sites of metastatic spread 1
• Noncontrast CT is specifically recommended for restaging, but either approach is acceptable for initial staging 1

Primary Site Evaluation

• Contrast-enhanced MRI of the primary site is the gold standard for evaluating local tumor extent, including involvement of the entire bone, adjacent joints, and soft tissue extension 1
• Plain radiographs of the primary site should be obtained initially and will typically show the characteristic "onion skin" periosteal reaction and mottled appearance 1
• CT of the primary site may be added to MRI if there is diagnostic uncertainty or if MRI is contraindicated 1

Whole-Body Metastatic Evaluation

• Whole-body FDG-PET/CT is the preferred modality for detecting distant bone and bone marrow metastases, with demonstrated 96% sensitivity and 92% specificity 1
• FDG-PET/CT has shown 100% sensitivity and 96% specificity for bone marrow involvement specifically, based on pooled data from multiple studies 1
• If FDG-PET/CT is unavailable, bone scintigraphy can be used as an alternative, though it is less sensitive 1

Spine and Pelvis Screening

• Screening MRI with or without contrast of the spine and pelvis should be considered, particularly given that pelvic primary tumors carry worse prognosis 1

Laboratory Studies

Prognostic Markers

• Serum LDH must be obtained as it has established prognostic value; elevated levels correlate with worse outcomes 1
• Complete blood count may reveal leukocytosis, which can be present at diagnosis 1

Pre-Treatment Baseline

• Renal function tests (urea, creatinine, glomerular filtration rate) are required before chemotherapy 1
• Cardiac function assessment (echocardiogram or MUGA scan) is necessary prior to anthracycline-based chemotherapy 1
• Audiogram should be obtained if cisplatin is planned 1

Tissue Diagnosis and Molecular Studies

Biopsy Considerations

• Staging should be completed BEFORE biopsy to avoid compromising subsequent treatment 1
• Image-guided core needle biopsy has high diagnostic yield for Ewing sarcoma and is the preferred approach 1

Molecular Analysis

• Cytogenetic and/or molecular studies must be performed on biopsy specimens to evaluate for t(11;22) translocation or other EWSR1 rearrangements, present in approximately 85% of cases 1
• The EWSR1::FLI1 fusion transcript is the most common finding 1
• CD99 (MIC2) expression should be assessed as it is characteristically strongly positive 1

Bone Marrow Assessment: The Evolving Standard

Bone marrow biopsy is no longer mandatory in the era of FDG-PET/CT imaging. 1

Evidence Supporting Omission of Routine Bone Marrow Biopsy

• FDG-PET/CT demonstrates 100% sensitivity and 96% specificity for detecting bone marrow involvement, with 100% negative predictive value 1, 2
• Only 1.2% of patients have bone marrow metastases as their sole metastatic site 2
• In a large single-institution study of 504 patients, only one patient (0.3%) had bone marrow involvement detected by biopsy with negative imaging 3
• A recent French study of 180 patients showed 92.3% sensitivity and 99.4% specificity for FDG-PET/CT in detecting bone marrow metastases 4

When to Consider Bone Marrow Biopsy

• Bone marrow biopsy may still be considered if metastatic disease is already detected on imaging, as it can identify a very high-risk subgroup who might benefit from different treatment strategies 1, 3
• If FDG-PET/CT is not available or shows equivocal findings, bone marrow biopsy should be performed 1

Critical Prognostic Information to Document

The staging workup should specifically assess these adverse prognostic factors that directly impact mortality:

• Presence of metastatic disease (5-year relapse-free survival: 22% with metastases vs. 55% without) 1
• Primary tumor location (pelvic tumors have significantly worse outcomes than distal extremity lesions) 1
• Tumor volume (>100 mL or diameter >8 cm indicates worse prognosis) 1
• Serum LDH level (elevated levels correlate with worse outcomes) 1

Common Pitfalls to Avoid

• Do not perform biopsy before completing staging, as poorly performed biopsies can compromise treatment and staging must guide biopsy planning 1
• Do not rely solely on bone scan when FDG-PET/CT is available, as PET/CT is superior for detecting both osseous and bone marrow metastases 1
• Do not omit chest CT, as pulmonary metastases are among the most common sites of spread and significantly impact prognosis 1
• Do not assume bone marrow biopsy is mandatory; in patients with localized disease on FDG-PET/CT, the yield is extremely low (0.3%) and the procedure can be omitted 3, 2, 4