Your pathology report for osteosarcoma

Osteosarcoma is a type of bone cancer and the most common type of sarcoma to start in bone. It usually affects teenagers and young adults, although it can also occur in older adults. The most common location for osteosarcoma is the long bone of the thigh, called the femur, but it can develop in any bone in the body.

Pathologists classify osteosarcomas into different types based on how the tumour looks under the microscope and where it is located in the bone. The most common type is called conventional osteoblastic osteosarcoma.

What causes osteosarcoma?

In most cases, the cause of osteosarcoma is unknown. However, some people are born with genetic conditions that increase the risk of developing this type of cancer. These include:

• Li-Fraumeni syndrome

• Hereditary retinoblastoma

• Bloom syndrome

What are the symptoms of osteosarcoma?

Common symptoms of osteosarcoma include:

• A painful lump or swelling over a bone, which may grow quickly.

• Bone pain, especially at night or during activity.

• Fractures (breaks) in the bone due to weakness caused by the tumour.

How is osteosarcoma diagnosed?

Osteosarcoma is usually diagnosed after a biopsy, which is a procedure that removes a small piece of tissue for examination under a microscope. A pathologist looks for osteoid (immature bone) being produced by cancer cells, which is the key feature of osteosarcoma.

After diagnosis, most people are treated with chemotherapy, followed by surgery to remove the tumour. The tissue removed during surgery is sent to a pathologist, who examines it to determine how much of the tumour is still alive and whether it was completely removed.

Are there different types of osteosarcoma?

Yes. Osteosarcoma is classified into histologic subtypes based on how the tumour cells look under the microscope. These subtypes also help determine the grade of the tumour and provide clues about how aggressive the cancer may be. Some subtypes are more common than others, and most are considered high grade.

Common histologic subtypes of osteosarcoma

• Osteoblastic osteosarcoma – The most common subtype. The tumour is made up of cells that produce large amounts of osteoid, the material that becomes bone.

• Chondroblastic osteosarcoma – The tumour produces both osteoid and cartilage, and may resemble a cartilage-forming tumour under the microscope.

• Fibroblastic osteosarcoma – The tumour cells look like fibroblasts, which are cells that normally make connective tissue. Osteoid is still present but may be less obvious.

• Telangiectatic osteosarcoma – A rare subtype with large blood-filled spaces. It can look like a benign bone cyst on imaging but is an aggressive form of osteosarcoma.

• Giant cell-rich osteosarcoma – This subtype contains many giant cells mixed with tumour cells that produce osteoid. It may look similar to a benign giant cell tumour.

• Small cell osteosarcoma – The tumour is made up of small, round blue cells and may resemble other small cell cancers. It is aggressive and high grade.

• Low-grade central osteosarcoma – A rare subtype that grows more slowly. It starts in the center of the bone and may look similar to normal bone under the microscope.

• Parosteal osteosarcoma – A low-grade tumour that grows slowly on the surface of the bone. It often affects the back of the femur (thigh bone).

• Periosteal osteosarcoma – A tumour that grows from the outer layer of the bone (periosteum). It is usually intermediate grade and less aggressive than high-grade types.

• High-grade surface osteosarcoma – A rare, aggressive tumour that forms on the surface of the bone and grows rapidly.

• Paget disease-associated osteosarcoma – This type develops in bones affected by Paget disease, usually in older adults. It is often high grade and has a poorer prognosis.

• Post-radiation osteosarcoma – A high-grade tumour that develops in an area that was previously treated with radiation therapy, often many years later.

• Epithelioid and anaplastic osteosarcoma – Rare subtypes with very abnormal cells that may resemble other types of cancer. These tumours are usually high grade and aggressive.

What does grade mean in osteosarcoma?

The grade of an osteosarcoma describes how abnormal the tumour cells look under the microscope and how quickly they are expected to grow and spread. Tumours with cells that look more like normal bone cells are considered low grade, while tumours with very abnormal, rapidly dividing cells are considered high grade.

Most pathology reports describe the grade using one of the following terms:

• Grade 1 (low grade) – Cells look relatively similar to normal bone cells and tend to grow slowly.

• Grade 2 (intermediate grade) – Cells are more abnormal and grow at a moderate rate.

• Grade 3 (high grade) – Cells look very abnormal and typically grow and spread quickly.

Some reports may describe the grade as low, intermediate, or high without assigning a number.

How is the grade determined?

For most osteosarcomas, the histologic subtype (the specific type of tumour based on how it looks under the microscope) determines the tumour grade. This means that once the pathologist identifies the subtype, the grade is usually known based on how that subtype behaves.

High-grade (grade 3) osteosarcomas include:

• Conventional osteoblastic, chondroblastic, and fibroblastic osteosarcoma
• Telangiectatic, small cell, and anaplastic osteosarcoma
• High-grade surface osteosarcoma
• Paget-associated and post-radiation osteosarcoma
• Extraskeletal osteosarcoma (arising in soft tissue instead of bone)

Intermediate-grade (grade 2) osteosarcomas include:

• Periosteal osteosarcoma

Low-grade (grade 1) osteosarcomas include:

• Parosteal osteosarcoma
• Low-grade central osteosarcoma (also called well-differentiated intramedullary osteosarcoma)

In many cases, the tumour grade does not need to be assessed separately because it is already implied by the subtype.

Why is tumour grade important?

Tumour grade is important because it helps predict how the tumour is likely to behave:

• Low-grade tumours are less likely to spread and usually have a good prognosis. However, they may still grow back in the same location if not completely removed.

• High-grade tumours are more likely to grow quickly and spread to other parts of the body, particularly the lungs. These tumours typically require a combination of chemotherapy and surgery.

What does extraosseous extension mean?

Extraosseous extension means the tumour has grown outside the bone and into surrounding soft tissues, such as muscles or joints. This finding is important because it is associated with a higher risk of recurrence and spread.

What if the tumour has grown into another part of the bone?

Some bones, like those in the spine or pelvis, have multiple parts. If the tumour has grown from one part into another, this is called adjacent bone invasion. This is also associated with a worse prognosis and can increase the pathologic tumour stage (pT).

How is treatment response evaluated?

If you received chemotherapy or radiation therapy before surgery, your pathologist will look at how much of the tumour is dead (non-viable) under the microscope. This is called the treatment effect. A 90% or greater response (meaning most of the tumour is dead) is associated with a better prognosis.

What does perineural invasion mean?

Perineural invasion means cancer cells are growing around or inside a nerve. This may allow the tumour to spread into nearby tissues. While perineural invasion is important in many types of cancer, it is rarely seen in osteosarcoma.

What does lymphovascular invasion mean?

Lymphovascular invasion means cancer cells are found inside blood vessels or lymphatic vessels. This is another way the tumour can spread to other parts of the body. Like perineural invasion, lymphovascular invasion is uncommon in osteosarcoma.

What is a margin and why is it important?

A margin is the edge of tissue removed during surgery. Pathologists examine the margins to see if any cancer cells are present at the cut edge:

• Negative margin – no cancer cells at the edge (preferred).

• Positive margin – cancer cells are seen at the edge, meaning some tumour may have been left behind.

Margins help determine whether additional treatment is needed. The most commonly described margins in osteosarcoma include:

• Proximal bone margin – the cut closest to the body.

• Distal bone margin – the cut farthest from the body.

• Soft tissue margins – any nearby muscle or fat removed.

• Blood vessel or nerve margins – if large vessels or nerves were removed with the tumour.

What are lymph nodes and why are they important?

Lymph nodes are small immune organs found throughout the body. Cancer cells can sometimes spread to them through lymphatic vessels. However, lymph node involvement is rare in osteosarcoma, so lymph nodes are not always removed.

If lymph nodes are removed, the pathologist will report:

• How many were examined.

• Whether any contain cancer cells.

• The size of the largest tumour deposit (if present).

Lymph node involvement is used to determine the nodal stage (pN) and may influence treatment decisions.

What is the pathologic stage for osteosarcoma?

The pathologic stage describes how far the tumour has grown and whether it has spread. Staging is based on the TNM system, which stands for:

• T (Tumour) – Size of the tumour and extent of growth.

• N (Nodes) – Whether cancer cells are found in nearby lymph nodes.

• M (Metastasis) – Whether cancer has spread to other parts of the body.

The T stage depends on the location of the tumour in the body and helps doctors understand how advanced the disease is.

T stage for tumours in the appendicular skeleton, trunk, skull, or face:

These are bones of the arms, legs, shoulder, pelvis (excluding the spine), and head.

• pT1 – The tumour is 8 cm or smaller in greatest dimension.

• pT2 – The tumour is larger than 8 cm in greatest dimension.

• pT3 – The tumour is seen in multiple separate areas of the same bone (discontinuous tumour nodules), which indicates a more aggressive tumour.

T stage for tumours in the spine:

The spine is made up of a series of vertebral bones. Staging here depends on how many vertebrae are involved and whether critical structures are affected.

• pT1 – The tumour is limited to one or two adjacent vertebral bones.

• pT2 – The tumour involves three adjacent vertebral bones.

• pT3 – The tumour involves four or more adjacent vertebral bones, or any non-adjacent vertebral bones.

• pT4 – The tumour has grown into the spinal canal or invaded major blood vessels. This is a more advanced and potentially dangerous stage.

T stage for tumours in the pelvis:

The pelvis is a complex structure made up of several bones. The T stage is based on the size of the tumour and how many bones are involved.

• pT1 – Tumour is limited to one pelvic bone and does not extend outside the bone (no extraosseous extension).

  • pT1a – Tumour is 8 cm or smaller.

  • pT1b – Tumour is larger than 8 cm.

• pT2 – Tumour involves one pelvic bone with extraosseous extension, or two pelvic bones without extraosseous extension.

  • pT2a – Tumour is 8 cm or smaller.

  • pT2b – Tumour is larger than 8 cm.

• pT3 – Tumour involves two pelvic bones with extraosseous extension.

  • pT3a – Tumour is 8 cm or smaller.

  • pT3b – Tumour is larger than 8 cm.

• pT4 – Tumour involves three pelvic bones or is growing across the sacroiliac joint into the spine.

  • pT4a – Tumour invades the sacral nerve openings (neuroforamina).

  • pT4b – Tumour grows around or into major blood vessels such as the external iliac artery or vein.

Other tumour stages:

• pT0 – No tumour is found in the tissue that was examined.

• pTX – The tumour cannot be staged because there is not enough information, such as when the tumour is received in small fragments or incompletely.

What is the prognosis for a person diagnosed with osteosarcoma?

The prognosis for osteosarcoma depends on several important factors, including:

• Whether the cancer has spread (metastasized) at the time of diagnosis.

• How well the tumour responds to preoperative (neoadjuvant) chemotherapy.

• The location of the tumour in the body.

• The surgical margins, or how completely the tumour is removed during surgery.

• The histologic subtype and tumour grade.

Factors associated with a better prognosis

People with high-grade osteosarcoma that is localized (has not spread) and located in the limbs (arms or legs) generally have a good long-term outlook. With modern treatment, which includes a combination of chemotherapy and surgery, more than 70% of people with localized disease are long-term survivors. A particularly good sign is when the tumour shows a strong response to chemotherapy, meaning that 90% or more of the tumour is dead (necrotic) when it is removed. In these cases, the 5-year survival rate can exceed 80%.

Factors associated with a worse prognosis

The outlook is generally worse for people with:

• Metastatic disease (tumour has spread to the lungs or other bones at the time of diagnosis).

• Poor response to chemotherapy (less than 90% tumour necrosis).

• Tumours in the spine, pelvis, or other central locations (axial skeleton).

• Large or bulky tumours that are harder to remove completely.

• Positive surgical margins, meaning some tumour cells may have been left behind after surgery.

People with metastatic or recurrent osteosarcoma have a lower survival rate, with fewer than 30% surviving long term despite treatment.

Treatment and impact on survival

The introduction of multiagent chemotherapy has significantly improved survival for people with osteosarcoma. Before chemotherapy was used, over 80% of patients treated with surgery alone died from the disease. Today, surgery combined with chemotherapy is the standard approach, and limb-sparing procedures are often used instead of amputation. In some cases where surgery is not possible, radiation therapy may be used to control the tumour.

Different subtypes of osteosarcoma, such as telangiectatic osteosarcoma (TAEOS) and small cell osteosarcoma (SCOS), generally have a similar outlook to conventional osteosarcoma, although SCOS may have a slightly worse prognosis.

Questions to ask your doctor

• What type and grade of osteosarcoma do I have?

• Has the tumour spread outside the bone or to other parts of the body?

• Were the surgical margins negative?

• Did the tumour respond to chemotherapy?

• Will I need additional treatment such as more chemotherapy, radiation, or surgery?

• What is my stage, and what does it mean for my prognosis?