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Endometrial cancer starts when cells in the endometrium (the inner lining of the uterus) start to grow out of control. Cells in nearly any part of the body can become cancer, and can spread to other parts of the body. To learn more about how cancers start and spread, see What Is Cancer?

About the uterus and endometrium

The uterus is a hollow organ, normally about the size and shape of a medium-sized pear. The uterus is where a fetus grows and develops when a woman is pregnant. It has 2 main parts (see image below):

• The upper part of the uterus is called the body or the corpus. (Corpus is the Latin word for body.)
• The cervix is the lower end of the uterus that joins it to the vagina.

When people talk about cancer of the uterus, they usually mean cancers that start in the body of the uterus, not the cervix. (Cervical cancer is a separate kind of cancer.)

The body of the uterus has 2 main layers:

• The myometrium is the outer layer. This thick layer of muscle is needed to push the baby out during birth.
• The endometrium is the inner layer. During a woman's menstrual cycle, hormones cause the endometrium to change. Estrogen causes the endometrium to thicken so that it could nourish an embryo if pregnancy occurs. If there is no pregnancy, estrogen is produced in lower amounts and more of the hormone called progesterone is made. This causes the endometrial lining to shed from the uterus and become the menstrual flow (period). This cycle repeats until menopause.

There is also a layer of tissue called the serosa which coats the outside of the uterus.

Types of endometrial cancer

Endometrial cancer (also called endometrial carcinoma) starts in the cells of the inner lining of the uterus (the endometrium). This is the most common type of cancer in the uterus

Endometrial carcinomas can be divided into different types based on how the cells look under the microscope. (These are called histologic types.) They include:

• Adenocarcinoma (most endometrial cancers are a type of adenocarcinoma called endometrioid cancer -- see below)
• Uterine carcinosarcoma or CS (covered below in the grading section)
• Squamous cell carcinoma
• Small cell carcinoma
• Transitional carcinoma
• Serous carcinoma

Clear-cell carcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, and serous adenocarcinoma are less common types of endometrial adenocarcinomas. They tend to grow and spread faster than most types of endometrial cancer. They often have spread outside the uterus by the time they're diagnosed.

Endometrioid cancer

Most endometrial cancers are adenocarcinomas, and endometrioid cancer is the most common type of adenocarcinoma, by far. Endometrioid cancers start in gland cells and look a lot like the normal uterine lining (endometrium). Some of these cancers have squamous cells (squamous cells are flat, thin cells), as well as glandular cells.

There are many variants (or sub-types) of endometrioid cancers including:

• Adenocarcinoma, (with squamous differentiation)
• Adenoacanthoma
• Adenosquamous (or mixed cell)
• Secretory carcinoma
• Ciliated carcinoma
• Villoglandular adenocarcinoma

Grading endometrial cancer

The grade of an endometrial cancer is based on how much the cancer cells are organized into glands that look like the glands found in a normal, healthy endometrium.

In lower-grade cancers (grades 1 and 2), more of the cancer cells form glands. In higher-grade cancers (grade 3), more of the cancer cells are disorganized and do not form glands.

• Grade 1 tumors have 95% or more of the cancer tissue forming glands.
• Grade 2 tumors have between 50% and 94% of the cancer tissue forming glands.
• Grade 3 tumors have less than half of the cancer tissue forming glands. Grade 3 cancers tend to be aggressive (they grow and spread fast) and have a worse outlook than lower-grade cancers.

Grades 1 and 2 endometrioid cancers are type 1 endometrial cancers. Type 1 cancers are usually not very aggressive and they don't spread to other tissues quickly. Type 1 endometrial cancers are thought to be caused by too much estrogen. They sometimes develop from atypical hyperplasia, an abnormal overgrowth of cells in the endometrium. (See Endometrial Cancer Risk Factors for more on this.)

A small number of endometrial cancers are type 2 endometrial cancer. 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. 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, undifferentiated carcinoma, and grade 3 endometrioid carcinoma. These cancers don’t look at all like normal endometrium and so are called poorly differentiated or high-grade.

Uterine carcinosarcoma (CS) starts in the endometrium and has features of both endometrial carcinoma and sarcoma. (The sarcoma is cancer that starts in muscle cells of the uterus.) In the past, CS was considered a different type of uterine cancer called uterine sarcoma (see below), but doctors now believe that CS is an endometrial carcinoma that's so abnormal it no longer looks much like the cells it came from (it's poorly differentiated).

Uterine CS is a type 2 endometrial carcinoma. CS tumors are also known as malignant mixed mesodermal tumors or malignant mixed mullerian tumors (MMMTs). They make up about 3% of uterine cancers.

Other types of cancer in the uterus

Uterine sarcomas start in the muscle layer (myometrium) or supporting connective tissue of the uterus. These include uterine leiomyosarcomas and endometrial stromal sarcomas. These cancers are not covered here, but are discussed in detail in Uterine Sarcoma.

Cancers that start in the cervix and then spread to the uterus are different from cancers that start in the body of the uterus. They're described in Cervical Cancer.