Classification of Endometrial Cancer

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The 2 main types of cancer of the uterus are: 1.) Endometrial carcinomas, which start in the cells of the inner lining of the uterus (the endometrium). Nearly all cancers of the uterus are this type. These cancers are the focus of the remainder of this information. 2.) Uterine sarcomas, which start in the muscle layer (myometrium) or supporting connective tissue of the uterus. 
Endometrial carcinomas can be divided into two main different types based on how the cells look under the microscope (histologic types). These include:

  • Type 1 endometrial cancer: Endometrioid adenocarcinoma (most endometrial cancers are endometrioid adenocarcinomas)
  • Type 2 endometrial cancer: Papillary serous carcinoma, clear cell carcinoma, or carcinosarcoma (They make up about 10-15% of uterine cancers).

Type 1 endometrial cancers are made up of cells in glands that look much like the normal uterine lining (endometrium). Some of these cancers contain squamous cells (squamous cells are flat, thin cells that can be found on the outer surface of the cervix), as well as glandular cells. A cancer with both types of cells is called an adenocarcinoma with squamous differentiation. If both the squamous cells and the glandular cells look malignant (cancerous), these tumors can be called adenosquamous (or mixed cell) carcinomas. The grade of an endometrial cancer is based on how much the cancer forms glands that look similar to those found in normal, healthy endometrium. In lower-grade cancers, more of the cancerous tissue forms glands. In higher-grade cancers, more of the cancer cells are arranged in a haphazard or disorganized way and do not form glands. Grade 1 tumors have 95% or more of the cancerous tissue forming glands. Grade 2 tumors have between 50% and 94% of the cancerous tissue forming glands. Grade 3 tumors have less than half of the cancerous tissue forming glands. Grade 3 cancers are called "high-grade." They tend to be aggressive and have a poorer outlook than lower grade cancers (grades 1 and 2). Type 1 endometrial cancers are thought to be caused by excess estrogen. They sometimes develop from atypical hyperplasia, an abnormal overgrowth of cells in the endometrium (see the risk factors section). Type 1 cancers are usually not very aggressive and are slow to spread to other tissues. Grades 1 and 2 endometrioid cancers are “type 1” endometrial cancers.

Type 2 endometrial cancer make up a smaller number of endometrial cancers. Experts aren’t sure what causes type 2 cancers, but they don’t seem to be caused by too much estrogen. Type 2 cancers include all endometrial carcinomas that aren’t type 1, such as papillary serous carcinoma, clear-cell carcinoma. These cancers don’t look at all like normal endometrium and so are called “poorly differentiated” or “high-grade.” Because type 2 cancers are more likely to grow and spread outside the uterus, they have a poorer outlook (than type 1 cancers). Doctors tend to treat these cancers more aggressively. 

Uterine carcinosarcoma (CS) starts in the endometrium and has features of both endometrial carcinoma and sarcoma. In the past, CS was considered a type of uterine sarcoma, but doctors now believe that CS is a carcinoma that is abnormal and so no longer looks much like the cells it came from (poorly differentiated). Uterine CS is considered a type 2 endometrial carcinoma. CS tumors are also known as malignant mixed mesodermal tumors or malignant mixed mullerian tumors (MMMTs).