Undifferentiated pleomorphic sarcoma

This article was last reviewed and updated on November 20, 2018
by Bibianna Purgina, MD FRCPC

Quick facts:

  • Undifferentiated pleomorphic sarcoma is a rare and aggressive type of cancer.

  • Most tumours start in adults and the most common location is the legs.

  • The diagnosis of pleomorphic sarcoma can only be made after a pathologist examines a tissue sample under the microscope.

Learn more

An undifferentiated pleomorphic sarcoma is a special type of cancer called a sarcoma. Sarcomas are cancers (malignant tumours) that develop from mesenchymal tissues. Normal mesenchymal tissues include tissues such as fat, muscle, tendons, ligaments, bone and cartilage. The type of mesenchymal tissue that an undifferentiated pleomorphic sarcoma arises from is currently unknown.

 
The cancers cells of undifferentiated pleomorphic sarcoma are called undifferentiated because they are so abnormal that they do not look like any normal cells in the body.  The word pleomorphic also describes the way the cancer cells look under the microscope. Pleomorphic cancer cells show a lot of variation in size and shape throughout the tumor.  

 

Most undifferentiated pleomorphic sarcomas occur in adults. The most common location is the lower extremities.

 
Sarcomas may undergo a process called dedifferentiation. For example, a well differentiated liposarcoma (a sarcoma that arises from fat) can change over time so that some of the cells no longer resemble normal fat. This process is called dedifferentiation and these cancers are then called dedifferentiated liposarcoma.  

 

Dedifferentiation can occur in any kind of sarcoma. When examined under the microscope, these dedifferentiated areas can look like an undifferentiated pleomorphic sarcoma, however, they are not classified as undifferentiated pleomorphic sarcoma as long as there is still some of the better 'differentiated' tumour present.

 
It can be difficult for a pathologist to tell the difference between an undifferentiated pleomorphic sarcoma and dedifferentiation of another sarcoma, for example, dedifferentiated liposarcoma, on a biopsy specimen.

 

Often, on a biopsy specimen, the pathologist will provide your clinician or surgeon with a list of possible diagnoses that includes an undifferentiated pleomorphic sarcoma and dedifferentiated sarcomas.  Often a final diagnosis cannot be made until the whole tumor is surgically removed and the pathologist is able to examine the entire specimen.

 
Undifferentiated pleomorphic sarcoma do not have any characteristic genetic changes that can be tested for at the present time.  Also, by immunohistochemistry, undifferentiated pleomorphic sarcoma does not stain for any mesenchymal lineage specific stains (such as stains for muscle, etc). For this reason it is often described as having a 'non-specific' immunohistochemistry profile.

 
After a pathologist makes a diagnosis of undifferentiated pleomorphic sarcoma or suggests this diagnosis as a possibility, patients are often treated first with chemotherapy and/or radiation therapy followed by surgery. The tumour is then removed completely as a resection specimen and sent to pathology for examination.

After surgical resection, the pathologist examines the tumour microscopically and provides your surgeon and oncologist with critical information required for your subsequent treatment.

Histologic grade

Grade is a word pathologists use to describe how different the cancer cells look and behave compared to normal cells in the same location. Undifferentiated pleomorphic sarcomas are given a grade based on an internationally recognized system created by the French Federation of Cancer Centers Sarcoma Group (FNCLCC).

 
According to this system, undifferentiated pleomorphic sarcomas are high grade tumors and receive a grade of 2 or 3.  Compared to low grade sarcomas, all undifferentiated pleomorphic sarcomas are associated with worse prognosis.

  
If you have been diagnosed with an undifferentiated pleomorphic sarcoma, your pathologist will determine the French Federation of Cancer Centers Sarcoma Group grade of your tumour by looking for three microscopic features: tumour differentiation, mitotic count, and necrosis. 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.

  • Tumour differentiation – Tumour differentiation describes how closely the cancer cells look like normal cells. Tumours that look very similar to normal cells are given are given 1 point while those that look very different from normal cells are given 2 or 3 points. Because the cells in undifferentiated pleomorphic sarcomas are unlike any normal cells, they are assigned 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.

  • Necrosis - Necrosis 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.

 

The final grade is based on the total number of points given to the tumour:

  • Grade 1 – 2 or 3 points.

  • Grade 2 – 4 or 5 points.

  • Grade 3 – 6 to 8 points.

Tumour size

After the tumour is completely removed your pathologist will measure it 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 greatest dimension.


Tumours less than 5 cm are associated with better prognosis.

Necrosis

Necrosis is a form of cell death and it commonly occurs in cancers (malignant tumours). Your pathologist will closely examine the tumour for evidence of necrosis. Necrosis is used to determine the tumour grade (see Histologic grade above).

 

The presence of necrosis is important, especially if you have received pre-surgery chemotherapy or radiation therapy, as this can be an indication of treatment response.  It can also be associated with worse prognosis in tumours that have not been treated yet with chemotherapy or radiation therapy.

Tumour extension

Most undifferentiated pleomorphic sarcomas tend to occur in deep sites and may be associated with deep muscles of the thigh or the psoas muscle in the abdomen/retroperitoneum. Undifferentiated pleomorphic sarcoma can grow into or around organs and bone. 

 

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 contain cancer cells will be described in your report.

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.

Lymphovascular invasion

Lymphatics and blood vessels are long tubes that allow fluid (lymph and blood, respectively) and cells to travel around the body. When cancer cells enter a lymphatic or blood vessel it is called lymphovascular invasion and is associated with a higher risk that cancer cells will travel (metastasize) to a lymph node or a distant site such as the lungs.

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 considered ‘negative’ when there are no cancer cells at the edge of the cut tissue. Alternatively, a margin is considered ‘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).

Margins will only be described in your report after the entire tumour has been removed.

Lymph nodes

Metastatic disease describes the process where cancer cells escape the main tumour and travel to another part of the body. Lymph nodes are small immune organs located throughout the body.

 

Many cancers can spread to the lymph nodes, but undifferentiated pleomorphic sarcoma 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.

If lymph nodes were removed as part of your surgery, then your report will include the total number of lymph nodes examined and the number that contain cancer cells.

Pathologic stage

​The pathologic stage for undifferentiated pleomorphic sarcoma 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 worse prognosis.

Pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.

Tumour stage (pT) for undifferentiated pleomorphic sarcoma

The tumour stage for undifferentiated pleomorphic sarcoma varies based on the body part involved. For example, a 5 centimeter tumour that starts in the head 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 centimeters in size.
T2 – The tumour is between 2 and 4 centimeters in size.
T3 – The tumour is greater than 4 centimeters 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 centimeters in size.
T2 – The tumour is between 5 and 10 centimeters in size.
T3 – The tumour is between 10 and 15 centimeters in size.
T4 – The tumour is greater than 15 centimeters in size.

Tumour stage for tumours starting in the abdomen 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 centimeters in size.
T2 – The tumour is between 5 and 10 centimeters in size.
T3 – The tumour is between 10 and 15 centimeters in size.
T4 – The tumour is greater than 15 centimeters in size.

 

Tumour stage for tumours starting in the space around the eye (orbit):
T1 – The tumour is no greater than 2 centimeters in size.
T2 – The tumour is greater than 2 centimeters 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 reliable evaluate the tumor 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 undifferentiated pleomorphic sarcoma 

Undifferentiated pleomorphic sarcoma is given an 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 undifferentiated pleomorphic sarcoma 

Undifferentiated pleomorphic sarcoma is given an 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. 

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 piece of the machine called a protein.

Some sarcomas have characteristic changes to the tumour DNA that can be found using molecular tests. Unfortunately, at our current level of understanding, undifferentiated pleomorphic sarcoma does not have any known characteristic molecular changes. 

 

Sometimes, your pathologist will perform molecular tests on your undifferentiated pleomorphic sarcoma to rule out other sarcomas. A negative molecular test (for example, a molecular test without an identified translocation or amplification) is consistent with an undifferentiated pleomorphic sarcoma.

 

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.  If your pathologist is certain that your tumor is an undifferentiated pleomorphic sarcoma, then no molecular testing may be done.

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