Osteosarcoma

by Bibianna Purgina, MD FRCPC
March 4, 2022

---

What is osteosarcoma?

Osteosarcoma is a type of bone cancer and the most common type of sarcoma to develop in a bone. Osteosarcomas more commonly affect teenagers but it can also affect adults. The most common site for osteosarcoma is the long bone of the thigh. Pathologists divide osteosarcomas into histologic types based on how the tumour cells look when examined under the microscope and where the tumour is located on the bone. The most common histologic type is conventional osteoblastic osteosarcoma.

How do pathologists make the diagnosis of osteosarcoma?

A pathologist typically diagnoses osteosarcoma after examining a small tissue sample that has been removed in a procedure called a biopsy.  Under the microscope, osteosarcoma looks like thin or thick strands of immature bone called osteoid mixed with cancer cells.

After the diagnosis, most patients are treated first with chemotherapy and then with surgery. During surgery, the tumour is removed completely as a resection. The resection specimen (removed tumour) is sent to a pathologist for examination. Your pathologist will examine the tumour under the microscope and give your surgeon and oncologist important information that will help guide your treatment.

Are there different types of osteosarcoma?

Yes, pathologists divide osteosarcoma into histologic types based on the way the cells look when examined under the microscope and where on the bone the tumour is growing. The histologic type of osteosarcoma is important because it is used to determine the grade (see Histologic grade below).

Histologic types of osteosarcoma include:

• Osteoblastic osteosarcoma.
• Chondroblastic osteosarcoma.
• Fibroblastic osteosarcoma.
• Telangiectatic osteosarcoma.
• Giant cell-rich osteosarcoma.
• Low-grade central osteosarcoma (also called well-differentiated intramedullary osteosarcoma).
• Paget disease-associated osteosarcoma.
• Parosteal osteosarcoma.
• Periosteal osteosarcoma.
• High-grade surface osteosarcoma.
• Epithelioid osteosarcoma.
• Anaplastic osteosarcoma.
• Small cell osteosarcoma.

How do pathologists grade osteosarcoma?

Pathologists divide osteosarcoma into different three grades – 1, 2, and 3 – based on how similar the tumour cells are to normal bone cells. The cells in a grade 1 tumours look the most like normal bone cells while the cells in a grade 3 tumour look the least like normal bone cells. Instead of numbers, some pathology reports use the terms low, intermediate, and high to describe the grade.

The grade is important because it is used to predict the behaviour of the tumour. For example, grade 1 tumours may come back in the same location (local recurrence) but it is rare for them to spread to more distant parts of the body. Grades 2 and 3 (high grade) tumours are more likely to spread to distant parts of the body and are usually associated with a worse prognosis.

For most bone tumours, the histologic type of the tumour determines the grade (see the section above for more information). The list below shows the grade associated with each histologic type of osteosarcoma.

Grade 3 (high grade) osteosarcomas:

• Osteoblastic osteosarcoma.
• Chondroblastic osteosarcoma.
• Fibroblastic osteosarcoma.
• Small cell osteosarcoma.
• Telangiectatic osteosarcoma.
• High-grade surface osteosarcoma.
• Paget disease-associated osteosarcoma.
• Extra-skeletal osteosarcoma (a tumour that starts outside of a bone).
• Post radiation osteosarcoma.

Grade 2 (intermediate grade) osteosarcomas:

• Periosteal osteosarcoma.

Grade 1 (low grade) osteosarcomas:

• Parosteal osteosarcoma.
• Intramedullary well-differentiated osteosarcoma.

Has the tumour spread into surrounding tissues?

Some larger osteosarcomas may break through the bone and grow into the surrounding tissue including muscle, tendons, or the joint space.  If this has occurred, you may see a description of extraosseous extension in your report.

Some bones are made up of multiple parts. If the osteosarcoma has grown from one part of a bone into another, your report will describe the tumour as invading adjacent bones. This is particularly important for tumours in the spine or pelvis because both of these bones are made up of multiple parts.

Tumour extension is used to determine the tumour stage (see Pathologic stage below). Tumours that grow outside of the bone (extraosseous extension) or between multiple bones are associated with a worse prognosis.

Has the tumour responded to treatment?

If you received chemotherapy before surgery, your pathologist will examine all the tissue sent to pathology to see how much of the tumour is still viable (alive). Pathologists use different systems to describe how effective your treatment is on osteosarcomas. Usually, your pathologist will describe how effective the treatment was as the percentage of the tumour that is dead. For example, if the tumour shows a 65% response to therapy, it means that 65% of the tumour is dead. Typically, osteosarcoma showing 90% or more response to therapy (meaning 90% of the tumour is dead and 10% or less of the tumour is still alive) is associated with a better prognosis.

What does perineural invasion mean?

Nerves are like long wires made up of groups of cells called neurons. Nerves send information (such as temperature, pressure, and pain) between your brain and your body. Perineural invasion means that cancer cells were seen attached to a nerve.

Perineural invasion is important because it is associated with a higher risk that the tumour will come back in the same area of the body after treatment. However, perineural invasion is very rarely seen in osteosarcoma.

What does lymphovascular invasion mean?

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels. Tumour cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of tumour cells from the tumour to another part of the body is called metastasis.

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Lymphovascular invasion increases the risk that tumour cells will be found in a lymph node or a distant part of the body such as the lungs. However, the tumour cells in osteosarcoma rarely show lymphovascular invasion or travel to a lymph node.

What is a margin?

A margin is the normal tissue that a surgeon cuts in order to remove the bone (or part of the bone) and the tumour from the body. There are different types of margins and the margins described in your report will depend on the type of surgery performed to remove the tumour.

Common margins for osteosarcoma include:

• Proximal bone margin – This is the part of the bone closest to the middle of your body.
• Distal bone margin – This is the part of the bone farthest from the middle of your body.
• Soft tissue margins – This is the cut edge of any none bone tissue that was removed at the same time as the tumour in the bone.
• Blood vessel margins – This is the cut edge of any large blood vessels removed at the same time as the tumour.
• Nerve margins – This is the cut edge of any large nerve removed at the same time as the tumour.

After the tumour has been removed, pathologists closely examine all margins under the microscope to determine the margin status – positive or negative. A negative margin is when there are no tumour cells at the edge of the cut tissue. A positive margin is when there are tumour cells at the edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will come back in the same place after treatment. This is called a local recurrence.

What are lymph nodes​?

Lymph nodes are small immune organs located throughout the body. Tumour cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of tumour cells from the tumour to a lymph node is called metastasis.

Your pathologist will carefully examine all lymph nodes for tumour cells. Lymph nodes that contain tumour cells are often called positive while those that do not contain any tumour cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain tumour cells. Finding tumour cells in a lymph node is associated with a worse prognosis. However, osteosarcoma cancer cells are very rarely found in a lymph node.

How do pathologists determine the pathologic stage for osteosarcoma?

​The pathologic stage for osteosarcoma is based on a system called the TNM staging system. This system is used around the world and was created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M) to determine the complete pathologic stage (pTNM). Your pathologist will give each category a number after examining your tissue sample under the microscope. In general, a higher number means more advanced disease and a worse prognosis.

Tumour stage (pT)

For bone cancers such as osteosarcoma, the primary tumour (pT) stage depends on where the tumour was located in your body.

Tumour stage – appendicular skeleton

If the tumour was located in your appendicular skeleton (the bones of your arms, legs, shoulder, trunk, skull, or face), it is given a tumour stage of 1, 2 or 3 based on the size of the tumour and whether the tumour was seen in multiple parts of the bone.

• pT1: Tumour is less than or equal to 8 cm.
• pT2: Tumour is greater than 8 cm.
• pT3: Tumour was seen in multiple parts of the bone (discontinuous tumour nodules).

Tumour stage – spine

If the tumour was located in your spine, it is given a tumour stage of 1, 2, 3, or 4 based on how far the tumour has grown.

• pT1: Tumour is only seen in one or two adjacent vertebral bones (bones of the spine and the space between them).
• pT2: Tumour is seen in three adjacent vertebral bones.
• pT3: Tumour is seen in four or more adjacent vertebral bones, or any nonadjacent vertebral bones.
• pT4: Tumour invades the spinal canal or great vessels.

Tumour stage – pelvis

If the tumour was located in your pelvis, it is given a tumour stage of 1, 2, 3, or 4 based on the size of the tumour and how far it has grown.

• pT1: Tumour is in one pelvic bone with no extraosseous extension (tumour is not growing outside of the bone).
  • pT1a: Tumour is less than or equal to 8 cm.
  • pT1b: Tumour is greater than 8 cm.
• pT2: Tumour is in one pelvic bone with extraosseous extension (tumour is growing outside the bone) or in two bones with no extraosseous extension (tumour is not growing outside the bone).
  • pT2a: Tumour is less than or equal to 8 cm.
  • pT2b: Tumour is greater than 8 cm.
• pT3: Tumour is in two pelvic bones with extraosseous extension (tumour is growing outside the bone).
  • pT3a: Tumour is less than or equal to 8 cm.
  • pT3b: Tumour is greater than 8 cm.
• pT4: Tumour is in three pelvic bones or crossing the sacroiliac joint.
  • pT4a: Tumour involves sacroiliac joint and extends into the sacral neuroforamen (space where the nerves pass through).
  • pT4b: Tumour surrounds the external iliac vessels or extends into a major pelvic vessel.

Other tumour stages

• pT0: No tumour cells were seen after all of the tissue was examined under the microscope. This means that there is no evidence of a primary tumour.
• pTX (primary tumour cannot be assessed): The pathologist could not determine the tumour size or the distance that it had grown. This may happen if the pathologist receives the tumour as several small pieces.

Nodal stage (pN)

Primary bone cancers are given a nodal stage of 0 or 1 based on whether there are cancer cells in one or more lymph nodes.

• pNX: The pathologist is sent no lymph nodes to examine.
• pN0: No tumour cells are seen in any lymph nodes.
• pN1: Tumour cells are found in one or more lymph nodes.

Metastatic stage (pM) 
Primary bone cancers are given a metastatic stage (pM) only if a pathologist has confirmed that tumour cells have travelled to another part of the body. They do so by examining tissue from that part of the body.

There are two metastatic stages in primary bone cancers:

• M1a: Tumour cells have travelled to the lungs.
• M1b: Tumour cells have travelled to other bones or another organ.

Because this tissue is not typically sent to the lab, the metastatic stage cannot be determined and is not included in your report.