Carcinosarcoma of the uterus is an uncommon and fast-growing cancer. It is described as biphasic because it contains two different kinds of cancer cells growing side by side.
One part is made of cells that resemble those lining the inside surfaces of organs. This is the carcinoma component. The other is made of cells that resemble the body’s supporting tissues, such as muscle or connective tissue. This is the sarcoma component.
Your report or an older record may call this a malignant mixed Müllerian tumor, usually shortened to MMMT. That is an outdated name for the same diagnosis, and carcinosarcoma is the preferred term.
This is worth understanding early, because the name suggests otherwise. Despite containing a sarcoma-like part, a carcinosarcoma begins as a carcinoma. Over time, some tumor cells change and take on the appearance of a sarcoma, but genetic testing shows both parts share the same origin.
Two things follow from this. Carcinosarcoma is grouped and staged with endometrial carcinomas rather than uterine sarcomas. It is also treated with the chemotherapy used for high-grade endometrial cancer rather than with sarcoma regimens. When the cancer spreads to other parts of the body, the deposits usually contain the carcinoma component rather than the sarcoma component. This further supports the idea that the carcinoma drives the disease.
Carcinosarcoma shares risk factors with other endometrial cancers and occurs most often after menopause. Two specific associations are recognized.
The underlying cause is not fully understood, but genetic changes within the tumor cells matter a great deal. Most of these tumors carry alterations in the TP53 gene, the same change seen in endometrial serous carcinoma.
The process usually begins with an endometrial biopsy, in which a pathologist removes a small sample of the lining and examines it under a microscope.
A biopsy may capture only one of the two components. When only the carcinoma part is sampled, the report describes a high-grade endometrial carcinoma, and the sarcoma component is found for the first time after surgery. If your diagnosis changed after your operation, this is the usual explanation.
Surgery generally removes the uterus, ovaries, fallopian tubes, and lymph nodes. Thorough examination matters here, because a substantial number of people already have disease outside the uterus at the time of diagnosis.
Carcinosarcoma shows a mixture of carcinoma and sarcoma. The two are often sharply separated, though they can also be intermingled.
The carcinoma component is high grade. It most often shows endometrioid or serous features, though clear cell and undifferentiated patterns also occur.
The sarcoma component is also high grade. Your report may describe it in one of two ways.
Other features are commonly present.
Immunohistochemistry is a laboratory test that uses antibodies to detect specific proteins inside cells. For most carcinosarcomas, it is not needed, because the two components are recognizable under the microscope on their own.
It is used in a few specific situations. It can confirm what kind of tissue the sarcoma component is imitating, such as staining for skeletal muscle proteins when rhabdomyosarcoma is suspected. It also helps when the specimen is fragmented, or when one of the two components is present in only a small amount.
The FIGO grading system used for endometrioid carcinoma is based largely on how much of the tumor grows in solid sheets. Carcinosarcoma is considered high grade by definition, so it is not assigned grades 1, 2, or 3.
For this tumor, the stage and other high-risk features described below provide more useful information than a grade.
Biomarkers are tests performed on tumor tissue to understand how a cancer is likely to behave and which treatments may work. Not every case is tested for every biomarker.
p53 is a protein that helps control cell growth and repair damaged DNA. An abnormal result, reported as aberrant, mutant-type, or abnormal expression, indicates that the TP53 gene is altered.
Abnormal p53 is very common in carcinosarcoma and is characteristic of this diagnosis. For tumors confined to the uterus, this result raises the stage under the current staging system.
Mismatch repair proteins fix small errors that occur during DNA replication. The four tested are MLH1, PMS2, MSH2, and MSH6. Results are reported as retained, meaning normal, or lost, meaning abnormal.
Loss is uncommon in carcinosarcoma. When it does occur, the tumor is described as mismatch repair deficient. This may raise the possibility of Lynch syndrome, and it identifies tumors that may respond to immunotherapy if the cancer is advanced or returns.
POLE is a gene involved in copying DNA accurately. Tumors with a POLE mutation carry very large numbers of DNA changes yet behave far better than their appearance suggests.
POLE mutations are rare in carcinosarcoma. When present, they carry a favorable outlook and lower the stage under the current staging system. Results are reported as mutated or wild-type.
The myometrium is the thick muscular wall of the uterus. Myometrial invasion means the tumor has grown from the lining into that wall. The pathologist measures the depth and usually reports it as a percentage of the full thickness.
For this diagnosis, whether the tumor invades the muscle at all matters most because it changes the stage. This differs from the older staging system, in which the threshold was half the wall thickness. Deep invasion is also associated with a higher risk of the cancer returning.
Cervical stromal invasion means the tumor has grown from the body of the uterus into the cervix’s supporting tissue. Involvement of only the surface lining of the cervix does not count. This finding may influence whether radiation therapy is recommended.
The uterus sits against the ovaries, fallopian tubes, vagina, bladder, and rectum. The fallopian tubes, ovaries, and attached ligaments are together called the adnexa. The pathologist examines the removed tissue and reports whether tumor cells are present. Spread beyond the uterus is relatively common at diagnosis with this tumor type, and it raises the stage.
Lymphovascular invasion means tumor cells have been seen inside small lymphatic channels or blood vessels. These pathways allow cells to reach lymph nodes or distant organs.
Your report will describe it as absent, focal, or substantial. It is relatively common in carcinosarcoma and often leads to a recommendation for additional treatment.
A margin is the edge of the tissue removed during surgery. The pathologist examines the margins for tumor cells. Depending on the operation, these may include the cervical margin, the vaginal cuff margin, the tissue on either side of the uterus, and the peritoneal surface.
A positive margin means tumor cells reach the cut edge and some cancer may remain. A negative margin means no tumor cells were found at the edges. Positive margins may lead to a recommendation for radiation therapy.
Lymph nodes are small immune organs that filter fluid draining from tissues. Cancer cells can travel to them and form a metastasis.
Nodes from the pelvis, and often from higher in the abdomen, are removed for this diagnosis and examined individually. The risk of nodal spread is higher than for most endometrial cancers. Your report will state how many were examined and how many contained cancer. When cancer is found, the size of the largest deposit determines the nodal stage.
The pathologic stage uses the TNM system from the American Joint Committee on Cancer, which describes the tumor (T), the lymph nodes (N), and distant spread (M).
Tumor stage (pT):
Nodal stage (pN): N0 means no tumor cells in the nodes examined. N0(i+) means only isolated tumor cells. N1mi and N1a describe involvement of pelvic nodes. N2mi and N2a describe involvement of nodes higher in the abdomen. The “mi” categories are used for deposits of 2 mm or less. NX means no nodes were examined.
Metastatic stage (pM): M1 means the cancer has spread to a distant site. This can only be assigned when tissue from that site has been examined, so most reports list it as MX and use imaging instead.
The International Federation of Gynecology and Obstetrics substantially revised the staging system in 2023, and the change matters for this diagnosis.
The current system divides endometrial cancers into two groups according to how they tend to behave. Carcinosarcoma sits in the higher-risk group, alongside serous carcinoma, clear cell carcinoma, undifferentiated carcinoma, and high-grade endometrioid carcinoma. Tumors in that group are staged differently from the rest.
Molecular results can change the stage for tumors confined to the uterus. An abnormal p53 result raises it to IICmp53abn, which applies to most carcinosarcomas. A POLE mutation lowers it to IAmPOLEmut, though this is rare here. Molecular results do not change stage III or stage IV disease.
Your report or your oncologist may use a stage that does not match what you have read elsewhere. The difference between the 2009 and 2023 systems likely explains it, and it is worth asking which one was used.
Carcinosarcoma carries a less favorable outlook than most endometrial cancers. Reported five-year survival across all stages is roughly 1 in 3, and that figure has changed little over several decades.
Stage remains the strongest factor, and tumors confined to the uterus do considerably better than those that have spread. Even so, recurrence is common in early-stage disease, and it usually appears outside the pelvis rather than locally. This is why chemotherapy is recommended for most people, including many whose tumor appeared confined to the uterus.
Published survival figures come from groups of patients and cannot tell you what will happen in your case. They do not account for your stage, your surgery, or the treatment you receive. Your own team is far better placed to discuss what the outlook means for you.
Because this diagnosis is uncommon and treatment involves several modalities, care at a center experienced with gynecologic cancers is generally recommended.