What are the diagnostic and treatment approaches for pediatric patients presenting with symptoms suggestive of bone tumors?

Symptoms and Diagnostic Approach to Pediatric Bone Tumors

Persistent non-mechanical bone pain lasting more than a few weeks should prompt immediate investigation for a possible bone tumor in pediatric patients. 1 This cardinal symptom is often the first indication of a potential malignancy and requires prompt evaluation to prevent delayed diagnosis.

Key Clinical Symptoms and Presentation

• Pain characteristics:

  • Persistent pain not related to activity
  • Night pain (present in approximately 35% of cases) 2
  • Pain that awakens the child from sleep
  • Pain unresponsive to over-the-counter analgesics

• Physical findings:

  • Swelling (appears later when tumor progresses through cortex) 1
  • Palpable mass (present in ~41% of cases) 2
  • Limp or altered gait (present in ~25% of cases) 2
  • Limb disuse or activity modification (present in ~79% of cases) 2
  • Functional impairment or decreased joint range of motion 3

Age-Related Diagnostic Considerations

The likely diagnosis of a suspected bone tumor varies by age:

• Under 5 years: Destructive bone lesions are most commonly metastatic neuroblastoma or Langerhans cell histiocytosis 1
• 5-40 years: Primary bone sarcomas are more common 1
• Over 40 years: Metastatic disease or myeloma are more likely 1

Initial Diagnostic Workup

1. Conventional radiographs in two planes should always be the first investigation 1

   • Note that 20% of patients may have negative radiographs at initial presentation, leading to a significantly prolonged interval to diagnosis (average 54 days vs. 20 days overall) 2

2. When malignancy cannot be excluded on radiographs:

   • Proceed to MRI of the whole compartment with adjacent joints 1
   • MRI is the best modality for local staging of extremity and pelvic tumors 1

3. CT scan should be used only in cases of diagnostic uncertainty to better visualize:

   • Calcification
   • Periosteal bone formation
   • Cortical destruction
   • Soft tissue involvement 1

Referral and Biopsy

All patients with suspected primary malignant bone tumors should be referred to a bone sarcoma reference center before biopsy. 1 This is critical as bone sarcomas are frequently difficult to recognize as malignant by clinicians, radiologists, and pathologists.

The biopsy should be performed at the reference center by:

• The surgeon who will carry out the definitive tumor resection, or
• A radiologist who is part of the multidisciplinary team 1

Biopsy Principles:

1. Minimize contamination of normal tissues
2. Core needle biopsies under imaging control are often appropriate
3. Ensure adequate sampling of representative areas
4. Send samples for microbiological culture when osteomyelitis is in the differential
5. Samples must be interpreted by an experienced pathologist 1

Open biopsies have significantly higher diagnostic success rates (94.1%) compared to percutaneous procedures (73.1%) 4.

Common Pediatric Bone Malignancies

1. Osteosarcoma

• Most frequent primary bone cancer (incidence: 0.2-0.3/100,000/year)
• Higher incidence in adolescents (0.8-1.1/100,000/year at age 15-19)
• Male:female ratio of 1.4:1
• Risk factors: previous radiation therapy, Paget disease, genetic syndromes (Li-Fraumeni, Werner, Rothmund-Thomson, Bloom, hereditary retinoblastoma) 1

2. Ewing Sarcoma

• Third most common primary malignant bone-associated sarcoma
• Median age at diagnosis: 15 years
• Male predilection of 1.5:1
• Anatomic distribution: 25% pelvic bones, 50% extremity tumors, also ribs and vertebral column
• Rare in African and Asian populations 1

Diagnostic Pitfalls to Avoid

1. Attributing symptoms to trauma: A recent injury does not rule out a malignant tumor and must not prevent appropriate diagnostic procedures 1

2. Delaying advanced imaging: In patients with persistent unilateral pain in suspicious locations, early MRI should be considered, especially when radiographs are negative 2

3. Inadequate biopsy technique: Improper biopsy approach can contaminate surrounding tissues and complicate future surgical resection 1

4. Overlooking night pain: While night pain is classically associated with bone tumors, it is present in only about 35% of cases and is not a sensitive indicator 2

5. Delayed referral: The average time to diagnosis from initial presentation is 19.5 days, but can be significantly longer with initial negative radiographs 2

Treatment Approach

Treatment typically involves a multidisciplinary approach:

• Patients with osteosarcoma and resectable Ewing sarcoma receive chemotherapy followed by surgical resection 3
• High-dose methotrexate with leucovorin rescue is a key component of osteosarcoma treatment 5
• Cisplatin is often included in combination chemotherapy regimens for bone sarcomas 6

Early diagnosis and prompt referral to specialized centers are crucial for improving outcomes in pediatric bone tumors, as treatment and prognosis have remained largely unchanged for the past three decades 7.