Osteosarcoma
Updates to Article Attributes
Osteosarcomas are malignant bone-forming tumours. They are the second most common primary bone tumour after multiple myeloma, accounting for ~20% of all primary bone tumours. They can be classified into primary and secondary forms, as well as histologic types, of which conventional osteosarcoma is the most common.
Epidemiology
Primary osteosarcoma typically occurs in young patients (10-20 years) with 75% taking place before the age of 20 because the growth centres of the bone are more active during puberty/adolescence 3.There is a slight male predominance.
Secondary osteosarcoma occurs in the elderly, usually secondary to malignant degeneration of Paget disease, extensive bone infarcts, post-radiotherapy for other conditions, osteochondroma, and osteoblastoma.
Associations
- Paget disease of bone
- irradiation
- Rothmund-Thomson syndrome
- fibrous dysplasia (more common in the polyostotic form)
- Mazabraud syndrome (rare)
Diagnosis
The diagnosis of osteosarcoma is based on a combination of typical radiographic and pathological features.
Diagnostic criteria
Diagnostic criteria according to the WHO classification of bone tumours (2020 - blue book) 9:
- imaging features of a bone tumour
- osteoid matrix with neoplastic bone formation
- permeative and destructive growth pattern
The following histological criteria are desirable:
- high-grade atypia of tumour cells
- frequent atypical mitotic figures
Diagnostic clues
Clinical and imaging-related characteristics indicating the diagnosis without the pathological information:
- bimodal age distribution in adolescents (10-20 years) and in elderly patients
- bone tumour with osteoid matrix, permeative growth and non-expansile cortical destruction
- location in a metaphyseal-diaphyseal region with epiphyseal extension
Clinical presentation
Patients often present with bone pain, occasionally accompanied by a soft-tissue mass or swelling. At times, the first symptoms are related to pathologic fracture.
Pathology
Location
Primary osteosarcomas typically occur at the metadiaphysis of long bones in the appendicular skeleton, most commonly at the following sites:
- femur: ~40% (especially distal femur)
- tibia: ~16% (especially proximal tibia)
- humerus: ~15%
Other sites are less common:
- fibula
- innominate bone (i.e. os coxae)
- mandible (gnathic osteosarcoma)
- maxilla
- vertebrae
Secondary tumours, on the other hand, have a much wider distribution, largely mirroring the combined incidence of their underlying conditions, and thus much have a higher incidence in flat bones, especially the pelvis (a favourite site of Paget disease).
Osteosarcomas can be further categorizedcategorised by anatomic relationship to the bone 3,8:
- intramedullary/central: ~80%
- surface: ~10-15%
- intracortical osteosarcoma: rare
- extraskeletal osteosarcoma: ~5%
High-grade osteosarcomas may occasionally present with skip metastases, which are non-contiguous smaller tumour foci in the same bone or in adjacent bone 11.
Classification
The WHO classification of bone tumorstumours lists the histologic types of osteosarcoma, which can be further organizedorganised by the state of underlying bone and site of origin within the bone:
- primary osteosarcoma
- intramedullary/central
- conventional osteosarcoma: most common (75-80%) and discussed in this article
- low-grade central osteosarcoma
- telangiectatic osteosarcoma
- small cell osteosarcoma
- surface
- intramedullary/central
- secondary osteosarcoma
Conventional osteosarcomas can be further divided by histological subtype:
- osteoblastic (most common)
- chondroblastic
- fibroblastic
Macroscopic appearance
Osteosarcomas are bulky tumours where a heterogeneous cut surface demonstrates areas of haemorrhage, fibrosis, and cystic degeneration. Their extension within the medullary cavity is often much more extensive than the bulky part of the tumour would suggest. Areas of bone formation are characteristic of osteosarcomas, with the degree of bone formation varying widely.
Microscopic appearance
Poorly formed trabecular bone is seen with (in the typical high-grade conventional subtype) cellular pleomorphism and mitoses. Variable amounts of fibrocystic and chondroblastic appearing cells may also be encountered.
Markers
Serum alkaline phosphatase (ALP) may be raised (particularly with advanced disease).
Radiographic features
Although plain radiography can provide a lot of information, MRI is used for local staging by assessing intraosseous tumour extension (e.g. growth plate/epiphysis, skip lesions) and soft-tissue involvement. Chest CT and bone scanning have a role in distant staging.
Plain radiograph
Conventional radiography continues to play an important role in diagnosis. Typical appearances of conventional high-grade osteosarcoma include:
- medullary and cortical bone destruction
- wide zone of transition, permeative or moth-eaten appearance
- aggressive periosteal reaction
- sunburst type
- Codman triangle
- lamellated (onion skin) reaction: less frequently seen
- soft-tissue mass
- tumour matrix ossification/calcification
- variable: reflects a combination of the amount of tumour bone production, calcified matrix, and osteoid
- ill-defined "fluffy" or "cloud-like" compared to the rings and arcs of chondroid lesions
- lung and nodal metastases may be ossified 10
- spontaneous pneumothorax may occur in patients with lung metastases
CT
The role of CT is predominantly utilised in assisting biopsy and staging. CT adds little to plain radiography and MRI in the direct assessment of the tumour. The exception to this rule is predominantly lytic lesions in which small amounts of mineralised material may be inapparent on both plain film and MRI 4.
MRI
MRI is proving an essential tool to determine accurate local staging and assessment for limb-sparing resection, particularly for evaluation of intraosseous tumour extension and soft-tissue involvement. Evaluation of the growth plate is also essential as up to 75-88% of metaphyseal tumours do cross the growth plate into the epiphysis 4.
-
T1
- soft tissue non-mineralised component: intermediate signal intensity
- mineralised/ossified components: low signal intensity
- peritumoral oedema: intermediate signal intensity
- scattered regions of haemorrhage will have a variable signal (see ageing blood on MRI)
- enhancement: solid components enhance
-
T2
- soft tissue non-mineralised component: high signal intensity
- mineralised/ossified components: low signal intensity
- peritumoral oedema: high signal intensity
Treatment and prognosis
Cure, if achievable, requires aggressive surgical resection often with amputation followed by chemotherapy. If a limb-salvage procedure is feasible, a course of multidrug chemotherapy precedes surgery to downstage the tumour, followed by wide resection of the bone and insertion of an endoprosthesis. The outcome depends on different factors such as age, sex, site, size, and type but the most important predictor is the histologic degree of necrosis post-induction chemotherapy; 90% histologic necrosis is associated with much better prognosis 6. Currently, the 5-year survival rate after adequate therapy is approximately 60-80% 4.
The most frequent complications of conventional osteosarcoma are a pathologic fracture and the development of metastatic disease, particularly to the bone, lung, and regional lymph nodes.
Differential diagnosis
General differential considerations include the following:
When the lesion is at the posteromedial distal femur, consider
Practical points
When planning to biopsy a potential sarcoma, the treating surgeon should be consulted to plan the biopsy track as this will require excision to reduce the chance of seeding. A poorly planned track that crosses compartments can result in a more extensive resection, potentially with poor outcomes for the patient.
-</ul><p>Secondary tumours, on the other hand, have a much wider distribution, largely mirroring the combined incidence of their underlying conditions, and thus much have a higher incidence in flat bones, especially the pelvis (a favourite site of <a href="/articles/paget-disease-bone">Paget disease</a>).</p><p>Osteosarcomas can be further categorized by anatomic relationship to the bone<sup> 3,8</sup>:</p><ul>- +</ul><p>Secondary tumours, on the other hand, have a much wider distribution, largely mirroring the combined incidence of their underlying conditions, and thus much have a higher incidence in flat bones, especially the pelvis (a favourite site of <a href="/articles/paget-disease-bone">Paget disease</a>).</p><p>Osteosarcomas can be further categorised by anatomic relationship to the bone<sup> 3,8</sup>:</p><ul>
-</ul><p>High-grade osteosarcomas may occasionally present with skip metastases, which are non-contiguous smaller tumour foci in the same bone or in adjacent bone <sup>11</sup>.</p><h5>Classification</h5><p>The <a href="/articles/who-classification-of-tumors-of-bone">WHO classification of bone tumors</a> lists the histologic types of osteosarcoma, which can be further organized by the state of underlying bone and site of origin within the bone:</p><ul>- +</ul><p>High-grade osteosarcomas may occasionally present with skip metastases, which are non-contiguous smaller tumour foci in the same bone or in adjacent bone <sup>11</sup>.</p><h5>Classification</h5><p>The <a href="/articles/who-classification-of-tumors-of-bone">WHO classification of bone tumours</a> lists the histologic types of osteosarcoma, which can be further organised by the state of underlying bone and site of origin within the bone:</p><ul>
- +<li>spontaneous pneumothorax may occur in patients with lung metastases </li>
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