Leiomyosarcoma



What is a leiomyosarcoma?

Leiomyosarcoma is a type of cancer made up of specialized smooth muscle cells. It is part of a group of cancers called sarcomas. Most leiomyosarcomas occur in adults. Leiomyosarcoma can arise anywhere smooth muscle cells are normally found. However, the most common locations for this tumour are the arms and legs (extremities), the uterus, and the abdominal cavity.

How do pathologists make this diagnosis?

The diagnosis can only be made after a tissue sample is examined under a microscope by a pathologist. A small tissue sample is usually removed in a procedure called a biopsy. After the diagnosis is made, your doctor will talk with you about the need to perform a second procedure to remove the rest of the tumour. This second procedure is called an excision or a resection.

When examined under the microscope leiomyosarcoma is made up of long thin smooth muscle cells. Because of their shape, pathologists often describe these cells as spindle cells. These same smooth muscle cells are also found in a non-cancerous type of tumour called a leiomyoma. In order to tell the difference between leiomyosarcoma and leiomyoma, your pathologist will look for the following three histologic features:

  • Dividing tumour cells – Tumour cells divide in order to create new cells. This process is called mitosis. A cell that is in the process of dividing is called a mitotic figure. Dividing tumour cells are typically found in leiomyosarcoma. In contrast, very few dividing cells should be found in a non-cancerous leiomyoma.
  • Abnormal looking tumour cells – Pathologists use the word atypical or atypia to describe cells that are abnormal-looking in shape, size, or colour. Atypical tumour cells are commonly found in leiomyosarcoma.
  • Dead or dying tumour cellsMalignant tumours (cancers) grow more quickly than benign (non-cancerous) tumours. As they grow, the tumour cells run out of energy and die. This kind of cell death is called necrosis. Necrosis may be seen in leiomyosarcoma. However, it is rare to see necrosis in a non-cancerous leiomyoma.

Your pathologist may also perform a test called immunohistochemistry to confirm the diagnosis. Immunohistochemistry allows your pathologist to see different types of proteins inside the tumour cells. When this test is performed on a tissue sample from a leiomyosarcoma the tumour cells will be positive or reactive for proteins normally found in smooth muscle in smooth muscle cells such as h-caldesmon, smooth muscle actin (SMA), and desmin. These immunohistochemical markers are also positive in leiomyoma so these results need to be considered in combination with the histologic features (see above) in order to make the correct diagnosis.

FNCLCC grade

Pathologists use the word grade to describe how different the cancer cells look and behave compared to normal smooth muscle cells. The grade can only be determined after a sample of the tumour has been examined under the microscope.

Leiomyosarcomas are given a grade based on an internationally recognized system created by the French Federation of Cancer Centers Sarcoma Group (FNCLCC). If you have been diagnosed with leiomyosarcoma, your pathologist will determine the French Federation of Cancer Centers Sarcoma Group grade of your tumour by looking for three microscopic features.

  • Tumour differentiation – Tumour differentiation describes how closely the cancer cells look like normal smooth muscle cells. Tumours that look very similar to normal smooth muscle cells are given 1 point while those that look very different from normal smooth muscle cells are given 2 or 3 points.
  • Mitotic count – A cell that is in the process of dividing to create two new cells is called a mitotic figure. Tumours that are growing fast tend to have more mitotic figures than tumours that are growing slowly. Your pathologist will determine the mitotic count by counting the number of mitotic figures in ten areas of the tumour while looking through the microscope. Tumours with no mitotic figure or very few mitotic figures are given 1 point while those with 10 to 20 mitotic figures are given 2 points and those with more than 20 mitotic figures are given 3 points.
  • NecrosisNecrosis is a type of cell death. Tumours that are growing fast tend to have more necrosis than tumours that are growing slowly. If your pathologist sees no necrosis, the tumour will be given 0 points. The tumour will be given 1 point if necrosis is seen but it makes up less than 50% of the tumour or 2 points if necrosis makes more than 50% of the tumour.

Your pathologist will give each feature a certain number of points (from 0 to 3) and the total number of points determines the final grade of the tumour.

  • Grade 1 – 2 or 3 points.
  • Grade 2 – 4 or 5 points.
  • Grade 3 – 6 to 8 points.

According to this system, leiomyosarcomas may be either low or high-grade cancers. Low-grade sarcomas have a grade of 1.  High-grade sarcomas have a grade of either 2 or 3. High-grade leiomyosarcomas are more likely to spread to other parts of the body and are associated with a worse prognosis.

Molecular tests

Each cell in your body contains a set of instructions that tell the cell how to behave. These instructions are written in a language called DNA and the instructions are stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes and each gene tells the cell how to produce a piece of the machine called a protein.

Some sarcomas have characteristic changes to the tumour DNA that we can find using molecular tests. Unfortunately, at our current level of understanding, leiomyosarcoma does not have any known characteristic molecular changes.

Sometimes, your pathologist will perform molecular tests on your tumour to rule out other sarcomas. Pathologists test for these molecular changes by performing either fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) on a piece of the tissue from the tumour.

This type of testing is more often done on the biopsy specimen. A negative molecular test (for example, a molecular test without an identified translocation or amplification) is compatible with a leiomyosarcoma. If your pathologist is certain that your tumour is a leiomyosarcoma, then no molecular testing may be done.

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

Tumour size

The tumour is measured in three dimensions but only the largest dimension is typically included in your report. For example, if the tumour measures 5.0 cm by 3.2 cm by 1.1 cm, the report may describe the tumour size as 5.0 cm in the greatest dimension. Tumours less than 5 cm are associated with a better prognosis.

Tumour extension​

Leiomyosarcomas can grow into or around adjacent organs and bones. Your pathologist will examine samples of the surrounding organs and tissues under the microscope to look for cancer cells. Any surrounding organs or tissue that contains cancer cells will be described in your report. Tumour extension is important because it is used to determine the pathologic tumour stage (see Pathologic stage below).

Treatment effect​

If you received chemotherapy and/or radiation therapy before the operation to remove your tumour, your pathologist will examine all the tissue sent to pathology to see how much of the tumour is still alive (viable). Most commonly, your pathologist will describe the percentage of tumour that is dead.

Perineural invasion

Nerves are like long wires made up of groups of cells called neurons. Nerves transmit information (such as temperature, pressure, and pain) between your brain and your body. Perineural invasion is a term pathologists use to describe cancer cells attached to a nerve.

Perineural invasion is important because cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the original tumour. For this reason, perineural invasion is associated with a higher risk that the tumour will come back in the same area of the body (local recurrence) after treatment.

perineural invasion

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 is important because it increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.

lymphovascular invasion

Margins

A margin is any tissue that was cut by the surgeon to remove the tumour from your body.  Depending on the type of surgery you have had, the margins can include bones, muscles, blood vessels, and nerves that were cut to remove the tumour from your body.

All margins will be very closely examined under the microscope by your pathologist to determine the margin status. Specifically, a margin is called negative when there are no cancer cells at the edge of the cut tissue. A margin is called positive when there are cancer cells at the edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment (local recurrence).

Margin

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 metastasis.

Many cancers can spread to the lymph nodes, but leiomyosarcoma does this very rarely. If lymph nodes were part of the surgery to remove your tumour, your pathologist will assess them under the microscope and report whether they are involved by tumour.

Lymph node

Pathologic stage

​The pathologic stage for leiomyosarcoma 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 more advanced disease and a worse prognosis.

Tumour stage (pT) for leiomyosarcoma

The tumour stage for leiomyosarcoma varies based on the area of the body where the tumour started. For example, a 5-centimetre tumour that starts in the head or neck will be given a different tumour stage than a tumour that starts deep in the back of the abdomen (the retroperitoneum). However, in most body sites, the tumour stage includes the tumour size and whether the tumour has grown into surrounding body parts.

Tumour stage for tumours starting in the head and neck

T1 – The tumour is no greater than 2 centimetres in size.
T2 – The tumour is between 2 and 4 centimetres in size.
T3 – The tumour is greater than 4 centimetres in size.
T4 – The tumour has grown into surrounding tissues such as the bones of the face or skull, the eye, the larger blood vessels in the neck, or the brain.

Tumour stage for tumours starting on the outside of the chest, back, or stomach and the arms or legs (trunk and extremities)

T1 – The tumour is no greater than 5 centimetres in size.
T2 – The tumour is between 5 and 10 centimetres in size.
T3 – The tumour is between 10 and 15 centimetres in size.
T4 – The tumour is greater than 15 centimetres in size.

Tumour stage for tumours starting in the abdomen including the digestive tract and organs inside the chest (thoracic visceral organs):

T1 – The tumour is only seen in one organ.
T2 – The tumour has grown into the connective tissue that surrounds the organ from which is started.
T3 – The tumour has grown into at least one other organ.
T4 – Multiple tumours are found.

Tumour stage for tumours starting in the space at the very back of the abdominal cavity (retroperitoneum):

T1 – The tumour is no greater than 5 centimetres in size.
T2 – The tumour is between 5 and 10 centimetres in size.
T3 – The tumour is between 10 and 15 centimetres in size.
T4 – The tumour is greater than 15 centimetres in size.

Tumour stage for tumours starting in the space around the eye (orbit):

T1 – The tumour is no greater than 2 centimetres in size.
T2 – The tumour is greater than 2 centimetres in size but has not grown into the bones surrounding the eye.
T3 – The tumour has grown into the bones surrounding the eye or other bones of the skull.
T4 – The tumour has grown into the eye (the globe) or the surrounding tissues such as the eyelids, sinuses, or brain.

If after microscopic examination, no tumour is seen in the resection specimen sent to pathology for examination, it is given the tumour stage pT0 which means there is no evidence of primary tumour.

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 leiomyosarcoma

Leiomyosarcoma is given a nodal stage between 0 and 1 based on the presence or absence of cancer cells in one or more lymph nodes. If no cancer cells are seen in any lymph nodes, the nodal stage is N0. If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined, and the nodal stage is listed as NX.  If cancer cells are found in any lymph nodes, then the nodal stage is listed as N1.

Metastasis stage (pM) for leiomyosarcoma

Leiomyosarcoma is given a metastatic stage between 0 and 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be assigned if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.

The metastatic stage can only be given if tissue from a distant site is sent for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined, and it is typically not included in your report.

by Bibianna Purgina, MD FRCPC (updated August 11, 2021)
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