Your pathology report for low-grade central osteosarcoma

Low-grade central osteosarcoma (LGCOS) is a rare type of bone cancer. It starts inside the medullary cavity, the central part of a bone where the bone marrow is found. LGCOS is called “low-grade” because the cancer cells look only mildly abnormal under the microscope and grow slowly compared to more aggressive forms of osteosarcoma.

The tumour is made up of fibroblastic cells (spindle-shaped cells that produce connective tissue) and neoplastic bone, which is bone formed by the tumour itself. Despite its slow growth, LGCOS is still a malignant tumour, meaning it can grow into surrounding tissues and return if not completely removed.

Other names for this tumour include well-differentiated intramedullary osteosarcoma.

Where in the body is low-grade central osteosarcoma usually found?

LGCOS most often affects the metaphysis of long bones, which is the part of the bone near the end where growth occurs. The femur (thigh bone) and tibia (shin bone) are the most commonly involved sites. In rare cases, LGCOS can occur in the jaw, pelvis, or small bones of the hands and feet.

Who gets low-grade central osteosarcoma?

LGCOS is very rare, accounting for only about 1–2% of all osteosarcomas. It typically affects young adults, with most cases occurring in people in their 20s or 30s. It appears to be slightly more common in females than in males.

What are the symptoms of low-grade central osteosarcoma?

Symptoms of low-grade central osteosarcoma include:

• Pain in the affected bone.

• Swelling or a noticeable lump near a joint.

• Symptoms that develop slowly over time; in some cases, the tumour may go undiagnosed for years.

Because LGCOS grows slowly, the symptoms may be present for a long time before diagnosis.

How is the diagnosis made?

The diagnosis is usually made after a biopsy, a procedure where a small sample of the tumour is removed and examined under a microscope. On imaging studies such as X-rays, CT, or MRI, LGCOS often appears as a large lesion with sclerotic (dense) or lytic (less dense) areas. It may show signs of bone destruction, especially in advanced cases.

Under the microscope, LGCOS appears as a tumour made of fibroblastic spindle cells with mild nuclear atypia (slightly abnormal-looking nuclei). These cells produce well-formed bony trabeculae (strands of immature bone). The tumour usually grows between and around the existing bone and may extend into the outer surface (cortex) or nearby soft tissue.

What other tests may be performed to confirm the diagnosis?

To help confirm the diagnosis and distinguish LGCOS from benign conditions, pathologists may perform additional tests such as immunohistochemistry and molecular tests.

Immunohistochemistry

This test uses special stains to look for specific proteins in the tumour cells. LGCOS often shows strong expression of MDM2 and CDK4. These proteins are frequently found in LGCOS but not in many benign bone conditions.

Molecular testing

Testing for MDM2 gene amplification is commonly used to confirm the diagnosis. The presence of extra copies of the MDM2 gene supports a diagnosis of LGCOS. In contrast, benign tumours like fibrous dysplasia usually do not show this change and often carry a different mutation (in the GNAS gene), which is not seen in LGCOS.

These tests are especially helpful when the tumour is difficult to distinguish from other bone conditions under the microscope.

What does grade mean for low-grade central osteosarcoma?

All LGCOS tumours are by definition low-grade. This means that the cancer cells look only slightly different from normal bone cells and grow more slowly than the cells in high-grade osteosarcoma.

Low-grade tumours are less likely to spread to other parts of the body but can grow into surrounding bone and soft tissue if not completely removed. In rare cases, LGCOS can develop areas of dedifferentiation, where part of the tumour transforms into a high-grade osteosarcoma. These high-grade areas are more aggressive and may require additional treatment such as chemotherapy.

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 LGCOS.

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 LGCOS.

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 is the pathologic stage for low-grade central 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 the number of bones 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 low-grade central osteosarcoma?

The prognosis for LGCOS is generally very good when the tumour is completely removed with wide surgical margins. The risk of metastasis (spread to other parts of the body) is less than 5%, and most patients are long-term survivors.

• 5-year survival rate: around 90%.

• 10-year survival rate: over 80%.

However, the tumour almost always comes back (recurs) if it is only partially removed or treated with curettage (scraping out the tumour rather than fully excising it). If the tumour shows areas of dedifferentiation, the outlook is less favorable, and chemotherapy may be needed.