Osteosarcoma - Bone -

This article will help you read and understand your pathology report for osteosarcoma.

by Bibianna Purgina, MD FRCPC, updated on July 30, 2020

Quick facts:

• Osteosarcoma is the most common type of bone cancer.
• Most patients with osteosarcoma are teenagers.
• The most common location is the upper leg.
• The most common type of osteosarcoma is called osteoblastic.

Anatomy of bone

Bones are a special type of tissue that support and protect our body. In total there are 206 bones in our body. Some bones (like the bones in our fingers) are very small while other bones (like the bone in our upper leg) are very big.

Normal bones develop when special cells called osteoblasts produce a substance called osteoid. Osteoid starts soft but becomes hard over time as minerals (such as calcium) are added to it. Osteoid that stays soft is called ‘immature’ bone. Osteoid that becomes hard and mineralized is called ‘mature’ bone.

What is osteosarcoma?

Osteosarcoma is a type of bone cancer. Osteosarcoma is part of a group of cancers called sarcomas. Sarcomas are cancers that develop from mesenchymal tissues such as fat, bone and muscle.

Osteosarcomas more commonly affect teenagers but they can also affect adults. The most common site for osteosarcoma is the long bone of the thigh. Osteosarcomas are the most common type of sarcoma to develop in a bone.

How do pathologists make this diagnosis?

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 osteoid (immature bone) mixed with cancer cells.

After the diagnosis, a patient is often 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 pathologist for examination. Your pathologist will examine the tumour under the microscope and give your surgeon and oncologist (cancer doctor) important information that will help guide your treatment.

What to look for in your pathology report after a biopsy

​Histologic type

There are different types of osteosarcoma and each one is called a histologic type. Your pathologist will determine the histologic type of your tumour after examining it under the microscope. The histologic type is based on the way the cells look and where on the bone the tumour is growing.

Histologic types of osteosarcoma include:

• Conventional osteosarcoma.
• 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.

Osteoblastic osteosarcoma is the most common histologic type of osteosarcoma.

The histologic type of osteosarcoma is important because it is used to determine the grade (see Histologic grade below).

Histologic grade

Grade is a word that pathologists use to describe the difference between the cancer cells and the cells normally found in the bone. Bone tumours are graded on a scale of 1 to 3. Grade 1 tumours considered low grade and grade 3 tumours are considered high grade.

For most bone tumors, the histologic type of the tumor determines the grade (see Histologic type above).  Most osteosarcomas are grade 3 (high grade), but some histologic types are grade 1 (low grade) or grade 2 (intermediate grade).

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.

Grade is important because it is used to predict the behavior 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 (metastasize).

Higher grade tumours (grade 2 and 3) are more likely to spread to distant parts of the body and are usually associated with worse prognosis.

What to look for in your pathology report after the tumour has been removed

Tumour size

This is the size of the tumour. The tumour is usually measured in three dimensions but only the largest dimension is described in your report. For example, if the tumour measures 4.0 cm by 2.0 cm by 1.5 cm, your report will describe the tumour as being 4.0 cm.

The tumour size is important because tumours over 5 cm are more likely to spread to other parts of the body such as the lung. The tumour size is also used to determine the tumour stage (see pathologic stage below).

Tumour extension​

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 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 worse prognosis.

Treatment effect​

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 alive (viable).

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 (therapy response).

For example, if your osteosarcoma shows 65% therapy response, it means that 65% of the tumour is dead.

Typically, an osteosarcoma showing 90% or more therapy response (meaning 90% of the tumour is dead and 10% or less of the tumour is still alive) is associated with better prognosis.

Perineural invasion

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 (local recurrence) after treatment. However, perineural invasion is very rarely seen in osteosarcoma.

Lymphovascular invasion

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.

Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer 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 cancer cells will be found in a lymph node or a distant part of the body such as the lungs. However, the cancer cells in osteosarcoma rarely show lymphovascular invasion or travel to a lymph node.

Margins

A margin is the normal tissue that a surgeon cuts in order to remove the bone (or part of the bone) and the tumor from the body. There are different types of margins depending on the kind of surgery you’ve had, including:

• 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 positive margin is when there are cancer cells at the edge of the cut tissue. A negative margin is when there are no cancer 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 (local recurrence).

Lymph nodes​

Lymph nodes are small immune organs located throughout the body. Cancer 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 cancer cells from the tumour to a lymph node is called a metastasis.

Your pathologist will carefully examine all lymph nodes for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.

Finding cancer cells in a lymph node is associated with worse prognosis. However, osteosarcoma cancer cells are very rarely found in a lymph node.

Pathologic stage

​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 your osteosarcoma 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 your osteosarcoma 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 your osteosarcoma 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 cancer cells are seen in any lymph nodes.
• pN1: Cancer 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 the cancer has traveled to another part of the body (metastasis). They do so by examining tissue from that part of the body.

There are two metastatic stages in primary bone cancers:

• M1a: The cancer has traveled to the lungs.
• M1b: The cancer has traveled 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.

You will see many of these terms in your final pathology report. Ask your doctor any questions you have about your pathology report or treatment.