Uterine carcinosarcoma

by Emily Goebel, MD FRCPC
September 6, 2024

Carcinosarcoma of the uterus is a rare and aggressive type of uterine cancer that contains both carcinoma (cancer of epithelial cells, which line the surface of organs) and sarcoma (cancer of the connective tissue). It starts from cells in the endometrium on the inside surface of the uterus.

Carcinosarcoma is considered a high grade cancer, meaning it tends to grow quickly and can spread to other parts of the body. This type of cancer was previously called malignant mixed Müllerian tumour (MMMT).

What are the symptoms of uterine carcinosarcoma?

The symptoms of carcinosarcoma can be similar to those of other uterine cancers. They may include:

• Abnormal uterine bleeding: This is the most common symptom, especially in postmenopausal women.
• Pelvic pain or discomfort.
• A feeling of pressure or fullness in the abdomen.
• Unusual vaginal discharge.
• Unexplained weight loss.

If you experience any of these symptoms, it’s important to consult a doctor for further evaluation.

What causes carcinosarcoma of the uterus?

The exact cause of carcinosarcoma is not fully understood, but it likely results from genetic changes in the cells of the uterus. Risk factors that may contribute to its development include:

• Age: Carcinosarcoma is more common in postmenopausal women.
• Previous radiation therapy: Radiation treatment for other cancers may increase the risk.
• Obesity and certain hormone imbalances may also play a role.

How is the diagnosis of uterine carcinosarcoma made?

The diagnosis of carcinosarcoma is made by examining a sample of the tumour under a microscope. To obtain the tissue, a biopsy or surgery to remove the tumour is required. Pathologists then look for the combination of carcinoma and sarcoma components in the tumour, confirming the carcinosarcoma diagnosis.

What does uterine carcinosarcoma look like under the microscope?

When examined under the microscope, the tumour comprises 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 resembles the connective tissue typically found in the uterus.  Heterologous means that the sarcoma looks like connective tissue not typically 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.

Immunohistochemistry

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, but it can be positive for proteins called desmin or actin. The entire tumour is usually strongly positive for p53.  If a part of the tumour looks like rhabdomyosarcoma, it will be positive for the muscle markers myogenin and MyoD1.

Myometrial invasion

The myometrium is the thick muscular layer of the uterus. Myometrial invasion occurs when the cancer spreads from the inner lining of the uterus (the endometrium) into the myometrium. The depth of myometrial invasion is important because the more deeply the tumour invades, the higher the risk of spreading to other body parts.

Most pathology reports for carcinosarcoma will describe the amount of myometrial invasion in millimetres and as a percentage of the total myometrial thickness. This information is used to stage the tumour and to plan treatment.

Cervical stromal invasion

Cervical stromal invasion means that the cancer has spread from the body of the uterus into the cervix, which is the lower part of the uterus that connects to the vagina. This type of invasion indicates a more advanced stage of cancer and may influence treatment decisions, such as the need for more extensive surgery or radiation therapy.

Invasion of surrounding organs or tissues

The uterus is closely connected to several other organs and tissues, such as the ovaries, fallopian tubes, vagina, bladder, and rectum. The term “adnexa” refers to the fallopian tubes, ovaries, and ligaments directly linked to the uterus. As a tumour grows, it can spread into any of these organs or tissues. In such cases, some parts of these organs or tissues may have to be removed along with the uterus. A pathologist will thoroughly examine these organs or tissues for tumour cells, and the findings will be detailed in your pathology report. The presence of tumour cells in other organs or tissues is significant, as it raises the pathologic tumour stage and is linked with a poorer prognosis.

Lymphatic and vascular invasion

Lymphatic invasion occurs when cancer cells enter the lymphatic system, a network of vessels that helps fight infection. Vascular invasion refers to cancer cells entering the blood vessels. Both lymphatic and vascular invasion are important because they can indicate that the cancer is more likely to spread (metastasize) to other parts of the body, including lymph nodes and distant organs. These findings are often included in a pathology report to help guide treatment decisions.

Margins

A margin refers to the edge of the tissue that is removed during surgery, such as a hysterectomy. After the surgery, pathologists examine the margins of the tissue under a microscope to check for any remaining cancer cells. In the case of carcinosarcoma of the uterus, several specific margins are carefully evaluated:

1. Cervical margin: This is the edge where the uterus meets the cervix. Pathologists examine this margin to see if the cancer has spread into or beyond the cervix.
2. Vaginal cuff margin: If the top portion of the vagina is removed along with the uterus, the pathologist will check the vaginal cuff margin to ensure no cancer cells are present at the surgical edge.
3. Parametrial margin: This margin includes the tissue around the uterus, including ligaments and connective tissue. It is examined to see if cancer has spread into these areas.
4. Peritoneal margin: If the peritoneum (the lining of the abdominal cavity) is removed, it will be examined to check for cancer cells in this area.

If any of these margins contain cancer cells, it is referred to as a positive margin, which may mean that some tumour cells were left behind after surgery. A negative margin means no cancer cells were found at the edges, suggesting that the tumour was completely removed. Clear margins are important for reducing the risk of the cancer returning, and positive margins may lead to recommendations for additional treatments, such as radiation therapy.

Lymph nodes

Lymph nodes are small, bean-shaped structures that are part of the lymphatic system, which helps fight infection and remove waste from the body. Lymph nodes contain immune cells that filter lymph fluid, which travels through lymphatic vessels, and help trap harmful substances like bacteria or cancer cells. Lymph nodes are located throughout the body, including in the pelvis and abdomen, close to the uterus.

In the context of carcinosarcoma, lymph nodes are examined because this type of cancer has a higher risk of spreading beyond the uterus, particularly to nearby lymph nodes. For this reason, your surgeon may remove lymph nodes from the pelvis or abdomen, which are then sent to the pathologist for examination under a microscope. This is done to check for the presence of metastatic cancer (cancer that has spread from the primary tumour to other areas of the body).

Examining lymph nodes is important for several reasons:

1. Determining the stage of cancer: If cancer cells are found in the lymph nodes, it indicates that the cancer has spread beyond the uterus, which may place the cancer in a more advanced stage.
2. Guiding treatment decisions: The presence of cancer in the lymph nodes can affect treatment options. Patients with lymph node involvement may require more aggressive treatments, such as radiation therapy or chemotherapy, to reduce the risk of recurrence.
3. Assessing prognosis: Lymph node involvement is associated with a higher risk of the cancer returning or spreading to other parts of the body. Knowing whether the cancer has spread to the lymph nodes helps doctors provide more accurate information about the patient’s prognosis.

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.

Micrometastasis

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

Macrometastasis

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

Pathologic stage (pTNM)

​The pathologic stage for uterine carcinosarcoma is based on the TNM staging system, an internationally recognized system 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

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

• N0 – No tumour cells were found in any 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.