Chondrosarcoma

by Bibianna Purgina, MD FRCPC
March 7, 2023

What is chondrosarcoma?

Chondrosarcoma is a type of cancer made up of cartilage. This kind of tumour can start within a bone or any other part of the body where cartilage is normally found. The most common locations for this tumour are the spine and pelvis. Non-bone sites of origin include the larynx. Chondrosarcoma typically affects older adults and is the second most common type of bone sarcoma.

What are the symptoms of chondrosarcoma?

For tumours that start in a bone, symptoms of chondrosarcoma include pain and swelling over the involved bone. Larger tumours can cause the bone to fracture (break) which can cause a sudden increase in pain and inability to use the affected body area. For tumours that start in a soft tissue site such as the larynx, symptoms can include difficulty breathing, voice changes, and trouble swallowing.

How is the diagnosis of chondrosarcoma made?

This diagnosis is usually made after a small sample of tissue is removed in a procedure called a biopsy. The biopsy is sent to a pathologist who examines the tissue under a microscope. In some cases, a biopsy may show features highly suspicious for chondrosarcoma, but the diagnosis can only be made after the entire tumour is removed and available for examination under the microscope.

What are the types of chondrosarcoma?

Pathologists divide chondrosarcoma 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 types of chondrosarcoma are conventional, clear cell, mesenchymal, and undifferentiated. The histologic type is used to determine the tumour grade.

Conventional chondrosarcoma

Conventional chondrosarcoma is the most common type of chondrosarcoma. These tumours typically start in a space on the inside of a bone called the medulla. Conventional chondrosarcomas are locally aggressive tumours which means they can grow into surrounding organs and tissues. Tumour cells from conventional chondrosarcoma, however, rarely spread to other parts of the body.

Clear cell chondrosarcoma

Clear cell chondrosarcoma is a very small growing tumour that is normally found in the femur or humerus. The tumour is made up of large cells that appear clear when examined under a microscope. Clear cell chondrosarcoma can grow into surrounding organs and tissues, especially if not removed completely. Tumour cells can also spread to other parts of the body such as the lungs.

Mesenchymal chondrosarcoma

Mesenchymal chondrosarcoma is an aggressive type of chondrosarcoma that commonly grows outside of the bone and into surrounding organs and tissues. The tumour is made up of small cells with a high nuclear-to-cytoplasmic ratio (the nucleus is large while the cytoplasm is small). Mesenchymal chondrosarcomas harbour a HEY1-NCOA2 fusion gene that can be identified by molecular tests such as fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS).

Dedifferentiated chondrosarcoma

Dedifferentiated chondrosarcoma is an aggressive type of chondrosarcoma that grows out of a pre-existing conventional type of chondrosarcoma. Pathologists use the term transformation to describe this change.

​How do pathologists grade chondrosarcoma?

The grade is a way of comparing the cells in a tumour to bone cells called chondrocytes. In general, tumours that look more like normal chondrocytes are given a lower grade while those that look less like normal chondrocytes are given a higher grade.

For conventional chondrosarcoma, the grade ranges from 1 (low) to 3 (high) and pathologists look for 3 microscopic features when determining the grade: cellularity (the number of cells in the tumour), cytologic atypia (how abnormal the tumour cells look compared to normal chondrocytes), and mitotic activity (the number of tumour cells dividing to create new tumour cells).

Unlike conventional chondrosarcoma, clear cell chondrosarcoma, mesenchymal chondrosarcoma, and dedifferentiated chondrosarcoma are always given the same grade. Specifically, clear cell chondrosarcoma is always called grade 1 (low grade) while mesenchymal and dedifferentiated chondrosarcoma are always called grade 3 (high grade).

Grade 1 chondrosarcoma

Grade 1 tumours are made up of cells that look very similar to normal chondrocytes. Grade 1 tumours are also typically described as hypocellular because they contain a relatively small number of tumour cells and are less cellular than higher grade (grade 2 and 3) chondrosarcomas.

Grade 2 chondrosarcoma

Grade 2 tumours are typically hypercellular which means they contain more tumour cells than a grade 1 chondrosarcoma. The cells in a grade 2 tumour are usually described as atypical because they look abnormal compared to normal chondrocytes and pleomorphic because there is noticeable variation between the cells in the tumour. Occasional mitotic figures (tumour cells dividing to create new tumour cells) may also be seen.

Grade 3 chondrosarcoma

Like grade 2 tumours, grade 3 tumours are hypercellular which means they contain a large number of tumour cells. The cells in a grade 3 tumour are also described as atypical because they look abnormal compared to normal chondrocytes and pleomorphic because there is noticeable variation between the cells in the tumour. Mitotic figures (dividing tumour cells) are commonly found throughout the tumour and areas of necrosis (cell death) are also usually seen.

Why is the grade important for chondrosarcoma?

The grade is important for chondrosarcoma because it is used to predict how the tumour will behave over time. For example, a grade 1 tumour can regrow in the same location after surgery but it is rare for the tumour cells to spread to more distant parts of the body. Higher-grade tumours (grades 2 and 3) are more likely to spread to distant parts of the body and are usually associated with a worse prognosis.

Has the tumour spread into surrounding organs or tissues?

Tumours that start in a bone can break through the outer surface of the bone and grow into the surrounding organs or tissue such as muscle, tendons, or the joint space. If this has occurred, it may be included in your report and is usually described as extraosseous extension. If the tumour has grown into another part of the bone, that will also be described in your report. Tumour extension is important because it is used to determine the pathologic tumour stage (pT).

What is a margin?

In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.

Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. The number of margins described in a pathology report depends on the types of tissues removed and the location of the tumour. The size of the margin (the amount of normal tissue between the tumour and the cut edge) also depends on the type of tumour being removed and the location of the tumour.

Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.

A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved. For example, additional treatment may not be necessary for a benign (non-cancerous) type of tumour but may be strongly advised for a malignant (cancerous) type of tumour.

What is the pathologic stage for chondrosarcoma?

​The pathologic stage for chondrosarcoma is based on the TNM staging system, an internationally recognized system originally 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 examine the tissue submitted and give each part a number. In general, a higher number means a more advanced disease and a worse prognosis. The pathologic stage will only be included in your report after the entire tumour has been removed. It will not be included after a biopsy.

Tumour stage (pT) for chondrosarcoma

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

Tumours in the appendicular skeleton

​These are bones of your appendages and include the arms, legs, shoulder, trunk, skull, and facial bones. A tumour from these regions is given a tumour stage from 1-3 based on tumour size and whether there is a separate tumour nodule(s).

• pT1: Tumor ≤ 8 cm in greatest dimension.
• pT2: Tumor > 8 cm in greatest dimension.
• pT3: Discontinuous tumours in the primary bone site.

Tumours in the spine

Tumours located in the spine are given a tumour stage from 1-4 based on the extent of tumour growth.

• pT1: Tumor confined to one vertebral segment or two adjacent vertebral segments.
• pT2: Tumor confined to three adjacent vertebral segments.
• pT3: Tumor confined to four or more adjacent vertebral segments, or any nonadjacent vertebral segments.
• pT4: Extension into the spinal canal or great vessels.

Tumours in the pelvis

Tumours located in your pelvis are given a tumour stage from 1-4 based on the size of the tumour and the extent of tumour growth.

• pT1: Tumor confined to one pelvic segment with no extraosseous (growing outside of the bone) extension.
  • pT1a: Tumor ≤ 8 cm in greatest dimension.
  • pT1b: Tumor >8 cm in greatest dimension.
• pT2: Tumor confined to one pelvic segment with extraosseous extension or two segments without extraosseous extension.
  • pT2a: Tumor ≤ 8 cm in greatest dimension.
  • pT2b: Tumor >8 cm in greatest dimension.
• pT3: Tumor spanning two pelvic segments with extraosseous extension.
  • pT3a: Tumor ≤ 8 cm in greatest dimension.
  • pT3b: Tumor >8 cm in greatest dimension.
• pT4: Tumor spanning three pelvic segments or crossing the sacroiliac joint.
  • pT4a: Tumor involves sacroiliac joint and extends medially to the sacral neuroforamen (space where the nerves pass through).
  • pT4b: Tumor encasement of external iliac vessels or presence of gross tumour thrombus in major pelvic vessels.

If your pathologist cannot reliably evaluate the tumour size or the extent of growth, it is given the tumour stage pTX (primary tumour cannot be assessed).  This may happen if the tumour is received as multiple small fragments.

Nodal stage (pN) for chondrosarcoma

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

• Nx – No lymph nodes were sent to pathology for examination.
• N0 – No cancer cells are found in any of the lymph nodes examined.
• N1 – Cancer cells were found in at least one lymph node.

Metastasis stage (pM) for chondrosarcoma

Primary bone cancers including chondrosarcoma are given a metastatic stage only if the presence of metastasis has been confirmed by a pathologist.  There are two metastatic stages in primary bone sarcomas, M1a and M1b.  If there are confirmed lung metastasis, then the tumor metastatic stage is 1a.