Bone Tumours — Osteosarcoma, Ewing Sarcoma, Giant Cell Tumour, Chondrosarcoma and Osteoid Osteoma

Three facts solve most bone-tumour questions before histology: the patient's age, the part of the bone involved (epiphysis, metaphysis or diaphysis) and the radiographic pattern (lytic or sclerotic, margin, periosteal reaction, matrix). Exams then add one molecular or histological clincher — a translocation, a marker or a cell type.

Among benign bone tumours, osteochondroma is the most common: a cartilaginous tumour that projects out of the metaphysis, usually of the femur or tibia. A review of benign bone tumours groups them into eight types — osteochondroma, osteoma, osteoid osteoma, osteoblastoma, giant cell tumour, aneurysmal bone cyst, fibrous dysplasia and enchondroma. Of these, GCT is known for local aggressiveness, and it accounts for about 20% of benign bone tumours in that review.

Osteosarcoma is a malignant mesenchymal tumour whose defining feature is production of malignant osteoid (woven bony matrix) by the tumour cells. Excluding haematological cancers, it is the most common primary malignancy of bone in adolescents. High-grade intramedullary (conventional) osteosarcoma makes up about 80%; 42% arise in the femur, 19% in the tibia and 10% in the humerus, and 75–90% of long-bone tumours sit next to the distal femoral, proximal tibial or proximal humeral physis.

• Risk factors: germline RB1 (hereditary retinoblastoma — risk rises further after radiotherapy; somatic RB1 mutations in 30–75% of tumours), Li-Fraumeni syndrome (TP53; up to 5% of children with osteosarcoma), Paget disease (about 1% develop osteosarcoma) and prior radiation (3% of cases, 4–40 years after exposure).
• Secondary osteosarcoma of older adults favours flat bones such as the pelvis, mirroring Paget disease.
• X-ray: permeative or moth-eaten destruction with a 'sunburst' pattern from aggressive periostitis and a 'Codman triangle' where the periosteum is lifted off the bone.
• Labs: alkaline phosphatase and LDH are checked at work-up for diagnosis and prognosis.
• Metastasis: 10–20% present with metastases; lungs take 60–70% of metastatic disease and skip lesions or distant bone metastases another 20–30%.
• Treatment: neoadjuvant chemotherapy → wide surgical resection → adjuvant chemotherapy. About two-thirds of children and adolescents achieve long-term cure.

Ewing sarcoma is the second most common primary bone malignancy of adolescents and young adults (median age 15). It is a small round blue cell tumour — the same morphological family as neuroblastoma, rhabdomyosarcoma, retinoblastoma and Wilms tumour. It has no well-established link with radiation, drugs or family history.

Treatment combines multiagent chemotherapy with local therapy — surgery, radiotherapy or both — after induction chemotherapy. This approach has raised five-year survival for localised disease from less than 20% to more than 70%, although recurrence remains common. The work-up includes molecular testing of the biopsy for t(11;22) and staging with chest CT, PET-CT, bone scan and MRI.

Giant cell tumour (GCT, osteoclastoma) is one of the commonest benign but locally aggressive bone tumours — 4–10% of all primary bone tumours and 15–20% of benign ones. It affects young adults aged 20–40 after skeletal maturity (fewer than 5% occur in skeletally immature patients), with a slight female predominance (1.3–1.5 : 1) and higher incidence in Asian populations.

• Sites: 44% around the knee, 10% distal radius, 6% proximal humerus, 13% hands and feet.
• Radiology: an eccentric, epiphyseal, expansile lytic lesion extending up to the subchondral bone, with a narrow zone of transition and non-sclerotic margins; septation gives the classic 'soap-bubble' appearance.
• Pathogenesis: neoplastic mononuclear stromal cells express RANKL, recruiting osteoclast-like giant cells from monocytic precursors.
• Molecular marker: H3F3A (histone H3.3) mutations in over 90%; immunostaining for H3.3 G34W is sensitive and specific.
• Behaviour: local recurrence in about 35%; metastasis in 1–5%, most often to the lungs, with metastasis correlating with local aggressiveness and recurrence.

Chondrosarcoma is a malignant cartilage-forming tumour that makes up about 20% of primary malignant bone tumours. Most patients are over 50, with a slight male predominance, and it usually arises in the pelvis or long bones. Conventional chondrosarcoma (85–90%) arises in normal bone; rarer secondary tumours develop in a pre-existing enchondroma or osteochondroma.

• X-ray / CT: chondroid matrix calcification in a 'rings and arcs' pattern, with endosteal scalloping; higher grades destroy the cortex and form soft-tissue masses.
• Ollier disease and Maffucci syndrome raise the risk of malignant change in an enchondroma to 10–40%.
• IDH1/IDH2 mutations are found in 50–70% of chondrosarcomas.
• Treatment: low-grade central lesions can be curetted; intermediate and high-grade, axial or pelvic tumours need wide en bloc excision.
• Chemotherapy is generally ineffective in conventional chondrosarcoma; radiotherapy is used after incomplete resection or for unresectable tumours.

Osteoid osteoma is a benign bone-forming tumour with no malignant potential. It consists of a small nidus of vascular osteoid surrounded by reactive sclerotic bone, and it most often affects the femur and tibia of patients aged 5–25 years, with males affected three times as often.

• Night pain relieved by aspirin or NSAIDs — the single most-tested clue.
• Cause of the pain: the nidus makes prostaglandins at 100–1000 times normal bone levels, stimulating nerve fibres in and around it.
• Size rule: an osteoid osteoma does not exceed 2 cm; a similar lesion larger than 2 cm is an osteoblastoma.
• Imaging: CT was more accurate than MRI for detecting the nidus in one comparison (63% of cases).
• Treatment: NSAIDs first; surgical excision of the nidus if pain does not respond to conservative management. Preoperative tetracycline with UV light can help the surgeon see the nidus, which takes up the drug.