Bone Tumors

Categories of bone tumors:

Matrix producing tumors

  • Chondrogenic — cartilage forming (includes osteochondroma, chondroma, chondroblastoma, chondromyxoid fibroma, chest wall hamartoma, chondrosarcoma)
  • Osteogenic — bone forming (includes osteoid osteoma, osteoma, osteosarcoma)

Non-matrix producing tumors

  • Includes giant cell tumor, giant cell granuloma, aneurysmal bone cyst, simple bone cyst, primary vascular neoplasms, nonossifying fibroma, Langerhans cell histiocytosis, Rosai-Dorfman disease, fibrous spindle-cell tumor

Round cell tumors

  • Includes Ewing’s sarcoma, lymphoma, plasmacytoma

Radiographic distinction

Benign: well circumscribed with thick, regular new bone formation; usually slower-growing, producing geographic bone destruction resulting in sclerotic rim.

  • Benign tumors: osteoma, osteoid osteoma, osteochondroma, osteoblastoma, enchondroma, giant cell tumor of bone, aneurismal bone cyst, fibrous dysplasia of bone.

Malignant: poorly circumscribed, growth forms multiple layers of poorly organized periosteal new bone (eg, "onionskin" appearance of Ewing’s sarcoma); slow-growing lesions will have moth-eaten lucencies, while faster-growing lesions will have permeative destruction.

  • Malignant primary tumors: osteosarcoma, chondrosarcoma, Ewing’s sarcoma, fibrosarcoma.

Overview of the Common Malignant Bone Tumors:

Osteosarcoma:

Epidemiology: Most common malignant bone tumor in Pediatrics

  • Approximately 2.4% of all childhood cancers, with 1000 new cases/year in the US.
  • Incidence peaks in the second decade, with 75% of patients between 15-25 yrs old. There is a second, smaller peak in adulthood (between ages of 50 and 60).

Clinical features:

  • Pain is usually dull and aching, often at night, and is the most common presenting symptom. Unilateral pain, especially with swelling, should be further evaluated.
  • Occurs mostly in the extremities such as the knee, femur, and humerus
  • Though pathologic fracture may be seen, systemic symptoms are uncommon. May be a history of minor trauma (sprain or strain).
  • Physical exam may reveal local tenderness, swelling or even deformity.
  • Metastasis most commonly to the lungs, liver, and brain.

Pathology:

  • No specific genetic mutations or chromosomal alterations associated with osteosarcoma, though patients with hereditary retinoblastoma have 1000x increased risk.
  • 70% of sporadic case demonstrate an altered Rb gene. Many rearrangements and multiplications of chromosome number have also been described; patients who have a "near-diploid" number of chromosomes have a more favorable prognosis.

Diagnosis and Monitoring:

  • Will see highly elevated serum alkaline phosphatase, may be 3x normal.
  • X-ray shows bone extension “Codman’s triangle” branching into surrounding soft tissue

Therapy:

  • Treatment consists of a combination of chemotherapy and surgery.
  • Limb-sparing surgery combined with preoperative chemotherapy has been shown to be as effective as amputation.
  • Chemotherapeutic agents include cisplatin, ifosfamide, and high-dose methotrexate with leucovorin rescue.
  • Most recent data shows 49% 5-year survival in the adolescent/young adult populations.

Ewing’s sarcoma

Epidemiology: The second most common malignant bone tumor in Pediatrics

  • Approximately 1% of all pediatric tumors, making it the second most common primary malignant bone tumor in this population.
  • Most common between ages 10-20, but 20-30% diagnosed before age 10. There are 3 cases/million Caucasians under age 21. Less common in Black and Asian populations. Rarely seen before age 5.
  • 1.5:1 Male to Female ratio.

Clinical features:

  • May have pain characterized by patient as mild to severe, intermittent to constant. Constitutional symptoms (fever, weight loss). Pain, swelling, erythema in the affected extremity.  
  • Most common sites pelvis (26%), femur (20%), chest wall (16%)
  • Presents as a pathologic fracture in only 10-15% of cases. 25% of patients will have metastasis to lung, bones, or marrow. Often metastasis is present on presentation.

Diagnosis and Monitoring

  • Biopsy necessary for definitive histologic diagnosis. Perform MRI or CT to determine extent of skeletal involvement.
  • Patients will typically have elevated LDH and alkaline phosphatase. LDH can be used as a marker to detect response to therapy as well as for recurrence.

Pathology:

  • 85% of Ewing’s cases have translocation t(11;22)(q24;q12), which is a fusion between EWS and either ETS transcription factor FLI-1 (90-95%) or ERG (5-10%). The EWS-FLI-1 fusion is associated with a more favorable prognosis.
  • 10% of Ewing’s is due to chromosome 22 and 21 translocation. Rarely, a p53 mutation is associated with Ewing’s sarcoma; when present, it carries a very poor prognosis.

Therapy:

  • The standard approach to treatment for Ewing’s sarcoma is wide surgical resection followed by adjuvant chemotherapy (agents include doxorubicin, actinomycin, dactinomycin, cyclophosphamide, vincristine). Adjuvant radiotherapy is controversial but has been shown to reduce local recurrence. 60-70% survival in localized disease and 20-40% in metastatic disease.

Overview of the Common Benign Bone Tumors in Children:

Osteoid Osteoma

Epidemiology:

  • Usually appears between the ages of 5 and 24. There is a 3:1 Male to Female ratio.
  • Makes up approximately 10% of benign bone tumors.

Clinical features:

  • Osteoid osteoma can be found in essentially any bone, though is most often found in lower extremities.
  • Patients primary complaint will be pain that is worst at night, though it can often be relieved with aspirin causing patients to tolerate it for a period before presenting. Leg length discrepencies, genu varus, and scoliosis may be seen.
  1. Diagnosis and Monitoring
  • X-ray displays a sclerotic lesion which  may contain a lytic defect. The best imaging modality is CT.
  • Biopsy will show areas of immature woven and/or trabecular bone as well as osteoblasts within sclerotic lesions

Therapy:

  • Surgical excision is usually sufficient, which can now be done percutaneously with CT guidance. Pain relief can be dramatic and immediate after resection.

Osteoblastoma: 

Epidemiology:

  • Usually appears between the ages of 10 and 35.

Clinical features:

  • Osteoblastoma usually is observed in long bones and posterior spine.
  • Patients will typically present with pain, but in this lesion the pain is poorly responsive to NSAIDs.
  • Patients may also present with Scoliosis

Diagnosis and Monitoring

  • X-ray displays a 2-10cm well-circumscribed lesion, which may be outlined by a shell of new bone.
  • On biopsy, irregular woven trebeculae will be lined by osteoblasts and will be well-vascularized.

Therapy:

  • Treatment can be achieved via extended curettage or resection. Intralesional excision has been shown to result in recurrence.

References

  1. Arndt C, Crist W. Common Musculoskeletal Tumors of Childhood and Adolescence NEJM July 29. 1999;342:342
  2. Bernstein M, Kovar H, Paulussen M, et al. Ewing's sarcoma family of tumors: current management. Oncologist. 2006 May;11(5):503-19 
  3. Paulussen M, Bielack S, Jürgens H, Casali PG, ESMO Guidelines Working Group. Ewing's sarcoma of the bone: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009 May;20 Suppl 4:140-2
  4. Picci P. Osteosarcoma (osteogenic sarcoma). Orphanet J Rare Dis. 2007 Jan 23;2:6.
  5. Birch JM, Pang D, Alston RD, et al. Survival from cancer in teenagers and young adults in England, 1979-2003. Br J Cancer 2008 Sep 2;99(5):830-5.
  6. Copley L, Dormans JP. Benign pediatric bone tumors. Evaluation and treatment. Pediatr Clin North Am 1996; 43:949.

Back to Table of Contents