Citation, DOI, disclosures and article data
At the time the article was created Frank Gaillard had no recorded disclosures.View Frank Gaillard's current disclosures
Osteosarcomas are malignant bone-forming tumors. They are the second most common primary bone tumor after multiple myeloma, accounting for ~20% of all primary bone tumors. In children, they are considered the most common primary bone tumor 12. They can be classified into primary and secondary forms, as well as histologic types, of which conventional osteosarcoma is the most common.
Primary osteosarcoma typically occurs in young patients (10-20 years) with 75% taking place before the age of 20 because the growth centers 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.
fibrous dysplasia (more common in the polyostotic form)
Mazabraud syndrome (rare)
The diagnosis of osteosarcoma is based on a combination of typical radiographic and pathological features.
Diagnostic criteria according to the WHO classification of bone tumors (2020 - blue book) 9:
imaging features of a bone tumor
osteoid matrix with neoplastic bone formation
permeative and destructive growth pattern
The following histological criteria are desirable:
high-grade atypia of tumor cells
frequent atypical mitotic figures
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 tumor with osteoid matrix, permeative growth and non-expansile cortical destruction
location in a metaphyseal-diaphyseal region with epiphyseal extension
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.
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)
Other sites are less common:
Secondary tumors, 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 favorite site of Paget disease).
Osteosarcomas can be further categorized by anatomic relationship to the bone 3,8:
High-grade osteosarcomas may occasionally present with skip metastases, which are non-contiguous smaller tumor foci in the same bone or in adjacent bone 11.
The WHO classification of bone tumors lists the histologic types of osteosarcoma, which can be further organized by the state of underlying bone and site of origin within the bone:
Conventional osteosarcomas can be further divided by histological subtype:
osteoblastic (most common)
Osteosarcomas are bulky tumors where a heterogeneous cut surface demonstrates areas of hemorrhage, fibrosis, and cystic degeneration. Their extension within the medullary cavity is often much more extensive than the bulky part of the tumor would suggest. Areas of bone formation are characteristic of osteosarcomas, with the degree of bone formation varying widely.
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.
Serum alkaline phosphatase (ALP) may be raised (particularly with advanced disease).
Although plain radiography can provide a lot of information, MRI is used for local staging by assessing intraosseous tumor extension (e.g. growth plate/epiphysis, joint 12, skip lesions) and soft-tissue involvement. Chest CT, bone scanning and PET have a role in distant staging 12.
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
tumor matrix ossification/calcification
variable: reflects a combination of the amount of tumor 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
The role of CT is predominantly utilized in assisting biopsy and staging. CT adds little to plain radiography and MRI in the direct assessment of the tumor. The exception to this rule is predominantly lytic lesions in which small amounts of mineralized material may be inapparent on both plain film and MRI 4.
MRI is proving an essential tool to determine accurate local staging and assessment for limb-sparing resection, particularly for evaluation of intraosseous tumor extension and soft-tissue involvement. Evaluation of the growth plate is also essential as up to 75-88% of metaphyseal tumors do cross the growth plate into the epiphysis 4. T1 is the best sequence to evaluate intramedullary tumor extension which maybe overestimated on T2 12.
soft tissue non-mineralized component: intermediate signal intensity
mineralized/ossified components: low signal intensity
peritumoral edema: intermediate signal intensity
scattered regions of hemorrhage will have a variable signal (see aging blood on MRI)
enhancement: solid components enhance
soft tissue non-mineralized component: high signal intensity
mineralized/ossified components: low signal intensity
peritumoral edema: high signal intensity
Bone scintigraphy can show increased activity (hot) at site of primary tumor as well as sites of bone and systemic metastases e.g. lung 12.
FDG PET is better than bone scintigraphy in detection of bone metastases. It will show increased SUV at sites of distant metastases. As there is no definite cutoff value for SUV level, it can be used in follow-up to evaluate the response to chemotherapy 12.
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 tumor, 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.
General differential considerations include the following:
When the lesion is at the posteromedial distal femur, consider
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.