Differential Diagnosis of Large Femoral Mass in a 2-Year-Old
In an otherwise healthy 2-year-old girl with a large femoral mass, the primary differential diagnoses are metastatic neuroblastoma and Langerhans cell histiocytosis, as these are the predominant destructive bone lesions in children under 5 years of age. 1
Age-Specific Diagnostic Framework
The patient's age is the single most critical factor narrowing the differential diagnosis:
For children <5 years old, destructive bone lesions are predominantly either:
Primary bone sarcomas become more likely only after age 5 years, making osteosarcoma and Ewing sarcoma statistically less probable in this 2-year-old patient 1
Additional Differential Considerations
Benign Lesions
While less likely to present as a "large mass," benign entities should be considered:
- Simple bone cyst - common in the proximal femur in children, often presents with pathologic fracture (50% of cases in one series) 2
- Aneurysmal bone cyst - accounts for 23.5% of proximal femoral lesions in children 2
- Fibrous dysplasia - represents 26.5% of proximal femoral lesions in pediatric patients 2
Infectious Etiology
- Osteomyelitis - must be differentiated from malignancy, as it outnumbers primary bone sarcomas and can mimic malignant lesions radiographically 1, 3
Soft Tissue Masses
If the mass is primarily soft tissue rather than bony:
- Infantile hemangioma - most common benign neoplasm of infancy (4-5% prevalence), though typically becomes evident within first weeks of life and would be unusual to present at 2 years 1
- Vascular malformations - venous malformations are most common (70%), though these typically don't present as acute large masses 1
- Lipoblastoma or other fat-containing masses - if fat is identified on imaging 4
Critical Diagnostic Algorithm
Immediate Imaging Sequence
Conventional radiographs in two orthogonal planes - mandatory first step 1, 5
MRI of entire femur with adjacent joints - if malignancy cannot be excluded on radiographs 1, 5
CT scan - selectively used to better visualize calcifications, periosteal bone formation, or cortical destruction 1
Systemic Staging (if malignancy suspected)
- Chest CT - evaluate for metastatic disease 1, 5
- Bone scintigraphy and/or whole-body MRI - assess for additional skeletal involvement 1, 5
- Neuroblastoma workup - if imaging suggests metastatic neuroblastoma, include urine catecholamines, MIBG scan 1
Critical Management Pitfalls
STOP: Do Not Biopsy Before Referral
All patients with suspected primary malignant bone tumors MUST be referred to a bone sarcoma reference center or specialized sarcoma network BEFORE any biopsy is performed. 1, 5, 6
- Children require centers with age-specific expertise 1, 5
- Inappropriate biopsy at non-specialized centers compromises treatment outcomes and survival 5, 6
- The biopsy must be performed by the surgeon who will perform definitive resection or by a dedicated interventional radiologist on that surgical team 1, 5
Key Clinical Red Flags
- Persistent non-mechanical pain - especially night pain, highly concerning for malignancy 1, 5, 6
- Progressive swelling - indicates tumor has breached cortex and distended periosteum 1, 6
- Duration >2-4 weeks - warrants immediate radiological assessment 5, 6
Common Diagnostic Errors to Avoid
- Do not assume trauma explains the mass - recent trauma does not rule out malignancy and must not delay appropriate diagnostic workup 6
- Do not dismiss osteomyelitis from differential - it frequently mimics malignancy and requires microbiological culture if suspected 1, 3
- Do not skip plain radiographs - they are mandatory first-line imaging and should never be bypassed 1, 5, 6