Uterine carcinosarcoma

by Emily Goebel, MD FRCPC
January 12, 2023

What is uterine carcinosarcoma?

Uterine carcinosarcoma is a type of cancer that develops in the uterus. It is called carcinosarcoma because, unlike most tumours, it is made up of two parts – a carcinoma and a sarcoma – that look different when examined under the microscope. Another name for carcinosarcoma is malignant mixed Mullerian tumour (MMMT).

What are the symptoms of uterine carcinosarcoma?

Symptoms of uterine carcinosarcoma include vaginal bleeding, pelvic or abdominal pain, and distension.

How is the diagnosis of uterine carcinosarcoma made?

Uterine carcinosarcoma is usually diagnosed after a small sample of tissue is removed from the endometrium in a procedure called a biopsy or curettage. Once the diagnosis is made, the tumour is removed in a resection specimen known as a hysterectomy.

What does uterine carcinosarcoma look like under the microscope?

When examined under the microscope, the tumour is made up of two parts – a carcinoma and a sarcoma. Both parts of the tumour are cancerous. The carcinoma part of the tumour is made up of abnormal epithelial cells. These cells are normally found on the inside of the endometrium. For that reason, the carcinoma part can look like other more common types of cancer that start in the endometrium including endometrioid carcinoma, serous carcinoma, or clear cell carcinoma. The sarcoma part is made up of abnormal spindle cells. These cells are normally found in connective tissue.

The sarcoma part can have homologous or heterologous elements. Homologous means that the sarcoma looks like the connective tissue normally found in the uterus, such as stroma or smooth muscle.  Heterologous means that the sarcoma looks like connective tissue not normally found inside the uterus, such as skeletal muscle (which pathologists call rhabdomyosarcoma) or cartilage (which pathologists call chondrosarcoma).  The presence of heterologous elements is important because it may be associated with a worse prognosis.

What other tests may be performed to confirm the diagnosis?

Your pathologist may perform a test called immunohistochemistry on your tissue sample to confirm the diagnosis. The carcinoma part is usually positive for proteins called cytokeratins. The sarcoma part may or may not be positive for cytokeratins, and can be positive for proteins called desmin or actin. The entire tumour is usually strongly positive for p53.  If there is a part of the tumour that looks like rhabdomyosarcoma (see above), it will be positive for the muscle markers myogenin and MyoD1.

What does myometrial invasion mean and why is it important?

The myometrium is a thick band of muscle just below the endometrium. The movement of tumour cells from the endometrium into the myometrium is called myometrial invasion. The amount of myometrial invasion will be described in millimetres and as a percentage of the total myometrial thickness. Myometrial invasion is an important prognostic feature and is used to determine the tumour stage.

What is the cervical stroma and why is it important?

The cervix is a structure at the very bottom of the uterus. The cervix connects directly with the endometrium. The wall of the cervix is made up of a type of tissue called the stroma. Uterine carcinosarcoma may grow from the endometrium into the cervix. After the tumour is removed completely, your pathologist will carefully examine the tissue from the cervix to see if there are any tumour cells in the cervical stroma. This examination is important because finding tumour cells in the cervical stroma increases the tumour stage

Has the tumour grown into other organs or tissues outside of the uterus?

Several other organs and tissues are directly attached to or are very close to the uterus including the ovaries, fallopian tubes, vagina, bladder, and rectum. Adnexa or adnexal are terms used to describe the fallopian tubes, ovaries, and ligaments connected directly to the uterus. As the tumour becomes bigger, it can grow directly into any of these organs or tissue. When this happens, parts of these other organs or tissues may need to be removed at the same time as the uterus. Your pathologist will carefully examine these other organs or tissues for tumour cells and the results will be described in your pathology report. Finding tumour cells in other organs or tissues is important because it increases the pathologic tumour stage and is associated with a worse prognosis.

What is lymphovascular invasion?

Lymphovascular invasion means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs.

What is a margin?

A margin is the normal tissue that surrounds a tumour and is removed with the tumour at the time of surgery. The margins will only be described in cases where the tumour extends into the cervical stroma or other tissues surrounding the uterus and after the entire tumour has been removed.

The type and number of margins described in your report will depend on the type of surgical procedure performed to remove the tumour. A margin is called positive when there are tumour cells at the very 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. A negative margin means that no tumour cells were seen at any of the cut edges of tissue.

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body such as a lymph node is called a metastasis.

Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node.

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist and the results of this examination will be described in your report. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.

The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.

What does it mean if a lymph node is described as positive?

Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy”.

What does it mean if a lymph node is described as negative?

Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy”.

What are isolated tumour cells (ITCs)?

Pathologists use the term ‘isolated tumour cells’ to describe a group of tumour cells that measures 0.2 mm or less and is found in a lymph node. If only isolated tumour cells are found in all the lymph nodes examined, the pathologic nodal stage is pN1mi.

What is a micrometastasis?

A ‘micrometastasis’ is a group of tumour cells that measures from 0.2 mm to 2 mm and is found in a lymph node. If only micrometastases are found in all the lymph nodes examined, the pathologic nodal stage is pN1mi.

What is a macrometastasis?

A ‘macrometastasis’ is a group of tumour cells that measures more than 2 mm and is found in a lymph node. Macrometastases are associated with a worse prognosis and may require additional treatment.

Is carcinosarcoma of the uterus given a FIGO grade?

All carcinosarcomas of the uterus are considered high-grade and are not graded according to the FIGO system.

What is the pathologic stage (pTNM) for uterine carcinosarcoma?

​The pathologic stage for uterine carcinosarcoma 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.

Tumour stage (pT) for uterine carcinosarcoma

Uterine carcinosarcoma is given a tumour stage between T1 and T4 based on the depth of myometrial invasion and growth of the tumour outside of the uterus.

• T1 – The tumour only involves the uterus.
• T2 – The tumour has grown to involve the cervical stroma.
• T3 – The tumour has grown through the wall of the uterus and is now on the outer surface of the uterus OR it has grown to involve the fallopian tubes or ovaries.
• T4 – The tumour has grown directly into the bladder or the colon.

Nodal stage (pN) for uterine carcinosarcoma

Uterine carcinosarcoma is given a nodal stage from N0 to N2 based on the examination of lymph nodes from the pelvis and abdomen.

• N0 – No tumour cells were found in any of the lymph nodes examined.
• N1mi – Tumour cells were found in at least one lymph node from the pelvis but the area with cancer cells was not larger than 2 millimetres (only isolated cancer cells or micrometastasis).
• N1a – Tumour cells were found in at least one lymph node from the pelvis and the area with cancer cells was greater than 2 millimetres (macrometastasis).
• N2mi – Tumour cells were found in at least one lymph node outside the pelvis but the area with cancer cells was not larger than 2 millimetres (only isolated cancer cells or micrometastasis).
• N2a – Tumour cells were found in at least one lymph node outside the pelvis and the area with cancer cells was greater than 2 millimetres (macrometastasis).
• NX – No lymph nodes were sent for examination.

Metastatic stage (pM) for uterine carcinosarcoma

Uterine carcinosarcoma is given a metastatic stage of M0 or M1 based on the presence of tumour cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is sent for pathological examination.