Conventional Osteosarcoma: Understanding Your Pathology Report

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Conventional osteosarcoma is the most common type of osteosarcoma, a cancer in which the tumor cells make new bone. It is a type of sarcoma, a cancer that starts in the body’s supporting and connecting tissues. Conventional osteosarcoma starts in bone, most often near the knee or shoulder, and makes up about 8 or 9 of every 10 osteosarcomas.

Conventional osteosarcoma is also called osteoblastic osteosarcoma. The name comes from osteoblasts, the cells that normally build new bone. Conventional osteosarcoma cells behave like abnormal osteoblasts because they make bone, and most of these tumors consist mainly of bone.

Conventional osteosarcoma is a high-grade cancer, which means it can grow quickly and spread to other parts of the body, most often the lungs. Treatment usually combines chemotherapy with surgery, and most people whose cancer has not spread are cured.

This article explains how doctors diagnose conventional osteosarcoma, what the three main types mean, and how to read the treatment effect, margins, and stage in your pathology report. Our article on chondroblastic osteosarcoma describes one type in more detail.

Who gets conventional osteosarcoma?

Conventional osteosarcoma most often affects teenagers and young adults, usually between the ages of 10 and 25. It often develops during the teenage growth spurt, when bones are growing quickly. It is slightly more common in males than in females.

A smaller second peak occurs in adults over 60. In this older group, the cancer sometimes develops in bone affected by an earlier condition, such as Paget disease of bone or past radiation treatment.

Most tumors develop near the end of a long bone, in an area called the metaphysis, where the bone grows in childhood. The most common sites are the lower end of the thigh bone (femur), the upper end of the shin bone (tibia), and the upper end of the arm bone (humerus). The pelvis, jaw, and spine are less common sites.

What causes conventional osteosarcoma?

Conventional osteosarcoma develops when bone-forming cells accumulate gene changes that allow them to grow out of control. In most people, these changes happen by chance during life, and no cause is found.

A small number of people have an inherited condition that raises the risk of osteosarcoma:

Li-Fraumeni syndrome. This condition is caused by an inherited change in the TP53 gene and raises the risk of several cancers. Our article on Li-Fraumeni syndrome explains it in detail.
Hereditary retinoblastoma. People born with a change in the RB1 gene can develop an eye cancer called retinoblastoma in childhood, and they have a higher risk of osteosarcoma later in life.
Rare inherited conditions. Rothmund-Thomson syndrome and a few other rare conditions also raise the risk.

Earlier radiation treatment to a bone and Paget disease of bone are the other known risk factors. Osteosarcoma that develops in these settings is called secondary osteosarcoma.

What are the symptoms?

The most common symptom of conventional osteosarcoma is pain in the affected bone, often near the knee or shoulder. The pain may come and go at first and is often worse at night or with activity.

Over weeks to months, a swelling or lump may develop over the bone. In some people, the weakened bone breaks after only a minor injury, a pathologic fracture. Because pain in a growing teenager is common, the diagnosis is sometimes delayed.

How is the diagnosis made?

Doctors diagnose conventional osteosarcoma by combining imaging with microscopic examination of tumor tissue. An X-ray usually shows a destructive area inside the bone, often with cloudy new bone and bone pushing out into the surrounding soft tissue.

An MRI shows how far the tumor extends inside the bone and into nearby muscle, nerves, and blood vessels. A chest CT scan and a bone scan or PET scan look for spread to the lungs and other bones.

A biopsy removes a small sample of the tumor for examination, usually with a needle. It should be planned with the surgical team at the center that will treat the cancer. The path of the biopsy needle is removed along with the tumor during surgery, so its position must match the surgical plan.

Under the microscope, a pathologist sees highly abnormal tumor cells that vary in size and shape, and many are dividing. The key finding is osteoid, the new, unhardened bone made directly by the tumor cells. Finding osteoid made by cancer cells is what confirms the diagnosis of osteosarcoma.

Special tests aren’t always needed, but when osteoid is scarce, the pathologist may perform immunohistochemistry for SATB2, a protein found in bone-forming cells. A positive result supports the diagnosis, although SATB2 is not specific to osteosarcoma. Other stains may be used to rule out similar-looking tumors.

Bone is hard, so we soften bone samples in a solution before cutting them thin enough to examine. This step can add one or more days to the time before the final report is ready.

What are the different types of conventional osteosarcoma?

The World Health Organization classification (5th edition, 2020) divides conventional osteosarcoma into three main types. The type is based on the tissue the tumor makes up most of, and many tumors contain a mix:

Osteoblastic osteosarcoma. Most of the tumor is bone and osteoid, and it is the most common type. Because it is so common, some reports use “osteoblastic osteosarcoma” as another name for conventional osteosarcoma.
Chondroblastic osteosarcoma. Much of the tumor is made of cartilage, with areas of osteoid. Because of the cartilage, it can look like a cartilage cancer called chondrosarcoma.
Fibroblastic osteosarcoma. Most of the tumor is made of long, thin spindle cells with only small amounts of osteoid.

All three types are treated similarly and have a similar outlook. Your report may also describe less common patterns, such as giant cell-rich or epithelioid areas. These patterns help the pathologist make the diagnosis but do not usually change treatment.

Other types of osteosarcoma, such as telangiectatic, small cell, parosteal, and periosteal osteosarcoma, are not conventional osteosarcoma. They look different under the microscope, and some behave differently.

Histologic grade

Grade describes how abnormal the tumor cells look and predicts how the tumor is likely to behave. Conventional osteosarcoma is high grade by definition, so every tumor of this type is treated as a high grade cancer.

Your report may say that the tumor is high grade. Other reports use the American Joint Committee on Cancer (AJCC) system, 8th edition, where grade 2 and grade 3 both count as high grade. Either number leads to the same treatment.

Tumor size

Conventional osteosarcoma size is measured after the tumor is removed and reported as the greatest length in centimeters. For tumors in the arms, legs, trunk, skull, and face, 8 cm separates the first two tumor stages.

Larger tumors are linked to a somewhat less favorable outlook, although size matters less than the response to chemotherapy and whether the cancer has spread.

Tumor extension

Conventional osteosarcoma starts in the hollow center of the bone, called the medullary cavity. As it grows, it can break through the bone’s hard outer layer and extend into the surrounding muscle and fat.

Your report will describe how far the tumor extends. It may also note whether the tumor has invaded the nearby joint, growth plate, or major nerves and blood vessels of the limb. These findings help the surgical team plan treatment and affect the pathologic stage.

The pathologist also looks for skip metastases, separate tumor deposits in the same bone not connected to the main tumor. When skip metastases are present, they raise the tumor stage.

Treatment effect

Most people with conventional osteosarcoma receive chemotherapy before surgery. After the tumor is removed, the pathologist examines slices from across the whole tumor to estimate how much of it is no longer alive. This is called treatment effect or tumor necrosis.

The result is reported as a percentage of nonviable (dead) tumor:

Good response. 90% or more of the tumor is nonviable. This is linked to a better outlook.
Poor response. Less than 90% of the tumor is nonviable. This is linked to a higher chance that the cancer will come back.

A poor response does not mean that treatment has failed, and many people with a poor response are cured. Adding more chemotherapy drugs after surgery for a poor response has not been shown to improve the outlook. Your team will explain how the result affects your post-surgery treatment.

Lymphovascular invasion

Lymphovascular invasion means that cancer cells are seen inside a blood vessel or lymphatic channel. In conventional osteosarcoma, cancer cells usually spread to the lungs through blood vessels. Your report may note lymphovascular invasion, but not every report includes this finding.

Surgical margins

A margin is the edge of tissue cut by the surgeon when a conventional osteosarcoma is removed. The pathologist examines the bone, soft tissue, and other margins to see whether any cancer cells reach the cut edge.

Negative margin. No cancer cells are seen at the cut edge. This suggests the tumor was completely removed. Your report will also give the distance from the tumor to the closest margin.
Positive margin. Cancer cells are seen at the cut edge. This suggests some tumor may remain, and further surgery or other treatment may be considered.

A positive margin is linked to a higher chance of recurrence at the same site, and a wider negative margin lowers that risk.

Lymph nodes

Conventional osteosarcoma rarely spreads to lymph nodes, so surgeons usually don’t remove them during surgery. Surgeons remove them only when imaging or the surgeon finds an abnormal node. If no lymph nodes were examined, your report may say that the nodal stage cannot be assessed.

Biomarker and molecular testing

For most people with conventional osteosarcoma, no biomarker test currently guides the choice of a specific targeted drug. Conventional osteosarcoma has many genetic changes, and these vary from one tumor to the next. No single change defines the cancer or predicts response to a particular treatment.

Molecular profiling

If the cancer comes back or does not respond to treatment, next-generation sequencing (NGS) may be performed on the tumor. This test looks for changes in many genes at once. A result may make a person eligible for a clinical trial. Your oncologist can tell you whether this testing is appropriate for you.

Testing for an inherited condition

Some people with conventional osteosarcoma are offered genetic testing for an inherited condition such as Li-Fraumeni syndrome. Testing is more likely to be offered when the cancer develops at a young age, or when there is a personal or family history of other cancers.

This test is performed on blood or saliva, not on the tumor. A positive result can affect cancer screening for you and your relatives, and a genetic counselor can explain what it means. A negative result means no inherited change was found in the genes tested.

More information about these tests is available in our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage of conventional osteosarcoma is based on the TNM system from the AJCC Cancer Staging Manual, 8th edition. It describes tumor size and whether it has spread to lymph nodes. Imaging usually detects spread to distant sites, such as the lungs, rather than the pathology report.

Tumor stage (pT)

For tumors in the arms, legs, trunk, skull, and face, the tumor stage is:

pT1. The tumor is 8 cm or smaller.
pT2. The tumor is larger than 8 cm.
pT3. More than one separate tumor is present in the same bone, such as a skip metastasis.
pTX. The tumor cannot be assessed, for example because it was removed in many pieces.

Tumors in the spine and pelvis are staged using different rules. These rules are based on how many parts of the spine or pelvis are involved and whether the tumor extends outside the bone.

Nodal stage (pN)

pN0. No cancer cells were found in the examined lymph nodes.
pN1. Cancer cells were found in at least one lymph node.
pNX. No lymph nodes were examined, which is the most common result for osteosarcoma.

Your oncologist combines the pathologic stage with the grade and imaging results to assign an overall stage group. The pathologic stage on your report is not the same as the overall stage.

What is the prognosis?

The outlook for conventional osteosarcoma depends mainly on whether the cancer has spread when it is first found. Before modern chemotherapy, most people treated with surgery alone died of the disease. Today, most people whose cancer has not spread are cured.

Cancer that has not spread. More than 7 in 10 people are alive and free of cancer in the long term. This means about 3 in 10 recur.
Cancer that has spread at diagnosis. Fewer than 3 in 10 people survive in the long term. The outlook is better when the spread is limited to a few lung spots that surgery can remove.
Response to chemotherapy. People with a good response, meaning 90% or more of the tumor is nonviable, do better. In this group, more than 8 in 10 people are alive five years after diagnosis.
Margins. A positive margin is linked to a higher chance of recurrence at the same site.
Tumor location and size. Tumors in the arms and legs do better than tumors in the pelvis or spine, which are harder to remove completely. Larger tumors also tend to recur more often than smaller ones.

Most recurrences happen within the first two to three years after treatment. When the cancer comes back, it most often returns in the lungs.

What happens after the diagnosis?

Conventional osteosarcoma is treated by a team at a center that specializes in bone cancer. The team usually includes an orthopedic oncologist, a medical oncologist, a radiologist, and a pathologist. A pediatric oncology team usually treats children and teenagers.

Chemotherapy before surgery. Treatment usually starts with about 10 weeks of chemotherapy. The most common combination is methotrexate, doxorubicin, and cisplatin, often called MAP.
Surgery. The tumor is removed in one piece with a rim of normal tissue around it, a procedure called a wide resection. In most people, surgeons can save the arm or leg and rebuild it with a metal implant or bone graft.
Chemotherapy after surgery. More chemotherapy is given for several months after surgery, and the treatment effect in your pathology report helps your team plan this part of treatment.
Mifamurtide. This drug helps the immune system attack cancer cells. The European Medicines Agency approved it in 2009 for young people whose cancer has not spread and has been completely removed. The US FDA has not approved it, and access varies by country.
Radiation therapy. Radiation is not usually part of treatment, but it may be considered when the tumor cannot be completely removed, such as in some tumors of the spine or pelvis.
Cancer in the lungs. Spots of cancer in the lungs, whether found at diagnosis or later, are often removed by surgery. This can still lead to a cure for some people.

After treatment, follow-up includes regular examinations and imaging of the surgical site and the chest for many years. Visits are most frequent during the first two to three years. Chemotherapy can affect the heart, hearing, kidneys, and fertility, so your team will also check for these effects over time. Clinical trials for osteosarcoma are ongoing, and your oncologist can tell you whether any are open to you.

Questions to ask your doctor

Which type of conventional osteosarcoma do I have: osteoblastic, chondroblastic, or fibroblastic?
How large is the tumor, and how far does it extend outside the bone?
Were any skip metastases found?
Has the cancer spread to my lungs or other bones?
What percentage of the tumor was nonviable after chemotherapy?
How will the treatment effect change my treatment after surgery?
Were the margins negative, and how close was the nearest one?
What is the pathologic stage, and what is my overall stage group?
Should I be offered genetic testing for an inherited condition?
Will molecular profiling of the tumor be done now or in the future?
Has a pathologist who specializes in bone tumors reviewed my case?
What long-term treatment effects should I watch for?
How often will I need follow-up visits and imaging?
Are there any clinical trials open to me?