Osteosarcoma

The most common primary malignant tumor of the bone accounting for 20% of cases. More than 50% of osteosarcoma tumors occur in the long bone around the knee. (1, 2)

Epidemiology

Osteosarcoma is mainly seen in adolescents and young adults with 75% of cases occurring patients less than 25 years old. (1)

It's the second most common malignancy in adolescents following hematological malignancies. (1)

Approximately 20% of osteosarcoma cases are metastatic at presentation. (1)

Primary Osteosarcoma

There are several genetic mutations that can play a role in primary osteosarcoma development. Here are a few of the more prominent ones (1, 3):

Li-Fraumeni Syndrome

Resulting from a germline mutation in the TP53 tumor suppressor gene. 12% of individuals with Li-Fraumeni Syndrome will develop an osteosarcoma.

Bloom syndrome

Resulting from mutations in the BLM gene, this syndrome predisposes patients to osteosarcoma. This gene normally helps provide stability to the DNA during replication

Werner syndrome

Mutations in the WRN gene resulting in premature aging as well as a host of other conditions including osteosarcoma.

Hereditary retinoblastoma

Germline mutation in the RB1 gene can be inherited and cause retinoblastoma. This mutation also confers an increased risk of developing osteosarcoma. Somatic RB1 mutations are related to 30% to 75% of osteosarcoma cases.

Rothmund-Thompson syndrome

Inherited RECQL4 mutation which predisposes patients to osteosarcoma.

Secondary Osteosarcoma

Secondary osteosarcoma typically results from Paget's disease and radiation exposure.

There are 6 defined subtypes of secondary osteosarcoma: Paget’s disease of the bone, radiation related, infarct related, osteosarcoma dye to chronic osteomyelitis, implant related, and osteosarcoma related with other disorders like fibrous dysplasia. (1)

Types of Osteosarcoma

Low grade central osteosarcoma

1-2% of cases. Predominantly in the long bones and is characterized by low mitotic activity.

Small Cell Osteosarcoma

1% of cases. Combination of Ewing sarcoma and osteosarcoma.

Secondary Osteosarcoma

Accounts for 4% of cases, usually in older individuals. Occurs in abnormal bone at the knee or hip.

Conventional Osteosarcoma

High grade sarcoma in the long bone making up 75%-80% of osteosarcoma cases.

Parosteal Osteosarcoma

Makes up <4% of cases. Located on the posterior distal femur in the majority of cases.

Telangiectatic Osteosarcoma

2%-12% of cases. Characterized by blood filled sinusoids.

Periosteal Osteosarcoma

<1% of cases. Typically located between the cortex and inner periosteal layer of the bone.

(1, 3)

Staging

Stage IA

Low grade, intra-compartmental, no metastasis

Stage IB

Low grade, extra-compartmental, no metastasis

One of the more commonly used systems for osteosarcoma staging is the Enneking staging system. (1)

Stage IIA

High grade, intra-compartmental, no metastasis

Stage IIB

High grade, extra-compartmental, no metastasis

Stage III

Metastasis present

Signs and Symptoms

Swelling over bone or bony part
Pain in bone or joint
Joint stiffness
Bone breaks for unknown reasons

(2, 4)

Treatment

This will depend on the specific situation. Usually some combination of surgery, chemotherapy, and radiotherapy are used. If it goes well patients can go into remission.

For example, one approach may be to use neoadjuvant chemotherapy (prior to main treatment), followed by surgery (see image of limb-sparing surgery on the right), and finally adjuvant chemotherapy (following main treatment). (1, 2)

(4)

Prognosis

Prognosis largely depends on what stage the osteosarcoma is upon diagnosis:

Localized

76% 5-year survival rate

Regional

64% 5-year survival rate

Distant

24% 5-year survival rate

(3)