Primary Malignant Bone Tumours

Primary malignant bone tumours are malignancies arising directly from bone or its supporting structures. Osteosarcoma and Ewing sarcoma together make up the overwhelming majority of those in children and adolescents.

Each has a characteristic, though overlapping, age distribution, anatomical predilection, and radiographic appearance.

• Osteosarcoma typically arises from osteoid-producing mesenchymal cells and characteristically affects the metaphyseal region of long bones around the knee.
• Ewing sarcoma arises from a distinct cell of origin within the Ewing sarcoma family of tumours and is defined by a specific chromosomal translocation. It more typically involves the diaphysis of long bones or, notably, the pelvis and flat bones.

Accurate diagnosis and full staging, delivered through specialist multidisciplinary orthopaedic oncology services, are essential given the implications for treatment and prognosis.

Pathophysiology and classification

• Osteosarcoma is malignant transformation of osteoblastic mesenchymal cells, producing characteristic immature osteoid matrix. Incidence peaks during the adolescent growth spurt, reflecting the association between rapid bone growth and tumour development.
• It most commonly arises around the knee (distal femur or proximal tibia) or proximal humerus, the sites of most active bone growth in adolescence.
• Ewing sarcoma is characterised by the defining t(11;22) translocation (or, less commonly, a variant translocation involving the same EWSR1 gene). This produces a fusion oncoprotein that drives the tumour biology.
• Its incidence peaks somewhat earlier than osteosarcoma, typically in children and adolescents. It characteristically affects the diaphysis of long bones and also tends to arise in the pelvis and other flat bones. This distinguishes it from the metaphyseal, long bone predominant pattern of osteosarcoma.
• Both malignancies have a substantial propensity for haematogenous metastatic spread, particularly to the lungs. Metastatic disease at diagnosis is the single most important adverse prognostic factor for both, so full staging at initial diagnosis is essential.

• The typical initial symptom of both tumours is localised bone pain. It is initially often intermittent and frequently attributed, by the child, family, or occasionally the first clinician, to a preceding minor trauma or to "growing pains".
• Distinguishing growing pains from a genuinely concerning presentation depends on careful attention to red flag features (see growing pains).
• The pain progresses over weeks to become persistent and, characteristically, increasingly severe, often with nocturnal exacerbation.
• As the tumour progresses, a palpable, often tender soft tissue mass, localised swelling, and sometimes restricted movement of an adjacent joint may develop. Pathological fracture through weakened, tumour-infiltrated bone is an important, though less common, presenting feature.
• Ewing sarcoma, frequently arising from the diaphysis or pelvis, may present with a more insidious, initially non-specific pattern of pain. Systemic symptoms (fever, malaise, and weight loss) may accompany it.
• This overlap can raise the initial consideration of infection, including osteomyelitis (see osteomyelitis), and is a recognised source of diagnostic confusion or delay.
• Any child or adolescent with persistent, unexplained, localised bone pain warrants prompt evaluation. This applies particularly with associated swelling, a palpable mass, pain disproportionate to any history of trauma, or pain persisting beyond the expected resolution of a straightforward musculoskeletal injury.
• Diagnostic delay is directly relevant to worse outcome in this time-sensitive group of malignancies.

• Plain radiography is the essential initial imaging investigation.
• Osteosarcoma characteristically shows a mixed lytic and sclerotic lesion with periosteal reaction. This includes the classical, though not universally present, "sunburst" pattern (radiating spicules of new bone formation) and Codman triangle (periosteal elevation at the margin of the tumour).
• Ewing sarcoma more typically shows a permeative, lytic lesion with a characteristic "onion skin" layered periosteal reaction.
• The two patterns overlap to some extent, and definitive diagnosis requires tissue confirmation rather than radiographic appearance alone.
• Magnetic resonance imaging of the primary tumour site gives essential, detailed characterisation of local extent, including the relationship to adjacent neurovascular structures and joints. It is needed for surgical planning.
• Tissue biopsy gives the definitive histopathological diagnosis. Ideally it is performed by, or in close consultation with, the surgical team that will undertake definitive resection, because biopsy tract planning is critical to avoid compromising subsequent limb-sparing options.
• Molecular and genetic characterisation, including confirmation of the characteristic Ewing sarcoma translocation, supports diagnostic confirmation.
• Full staging is an essential, standard part of evaluation and informs treatment planning and prognosis. It includes computed tomography of the chest (both tumours tend to spread to the lungs) and bone scan or, increasingly, positron emission tomography combined with computed tomography (to assess for additional osseous metastases).
• For Ewing sarcoma specifically, staging also includes bone marrow assessment, as marrow involvement is recognised though less common than pulmonary spread.

• Both osteosarcoma and Ewing sarcoma are managed with combined modality treatment: systemic chemotherapy plus local tumour control.
• Local control is surgical resection. For Ewing sarcoma, radiotherapy is an important additional, or in some cases alternative, modality, because this tumour is generally more radiosensitive than the relatively radioresistant osteosarcoma.
• The standard sequence for osteosarcoma is neoadjuvant (preoperative) chemotherapy, definitive surgical resection, then adjuvant (postoperative) chemotherapy.
• The histological response to neoadjuvant chemotherapy, assessed at resection as the proportion of tumour necrosis achieved, is an important, well established prognostic factor that informs further treatment.
• Limb-sparing resection, using endoprosthetic reconstruction or, in selected cases, biological reconstruction, is now the standard surgical approach for the great majority of extremity osteosarcoma and Ewing sarcoma. It has largely replaced the historically routine use of amputation.
• Amputation remains appropriate, and sometimes necessary, where tumour extent or relationship to critical neurovascular structures precludes safe, oncologically adequate limb-sparing resection.
• Ewing sarcoma treatment similarly uses neoadjuvant chemotherapy, then local control, then adjuvant chemotherapy. Local control is surgical resection, radiotherapy, or in some cases both, individualised by tumour location and response to initial treatment.
• The overall course typically extends over many months because of the intensive, multimodal protocols.
• Metastatic disease at diagnosis needs more intensive systemic treatment. Where feasible, add aggressive local control of the primary tumour and any resectable metastases. This is particularly relevant for isolated pulmonary metastases, where surgical resection may be part of the plan.
• Prognosis in metastatic disease is substantially less favourable, though not uniformly hopeless.
• Long-term multidisciplinary follow up covers disease surveillance, rehabilitation after limb-sparing surgery or amputation, and monitoring for late effects of intensive chemotherapy (including anthracycline cardiotoxicity, ototoxicity, and secondary malignancy risk).
• Provide psychosocial support for the child and family throughout the demanding, prolonged treatment course.