Leukemia (Blood Cancer)

 Endometrial carcinoma, or endometrial cancer, is when malignant or cancer cells arise in the glands of the endometrium, the lining of the uterus. The uterus is a hollow organ that sits behind the urinary bladder and in front of the rectum. The top of the uterus above the openings of the fallopian tubes is called the fundus, and the region below the openings is called the uterine body. The uterus tapers down into the uterine isthmus and finally the cervix, which protrudes into the vagina.

Zooming into the cervix, there are two openings, a superior opening up top, and an inferior opening down below, both of which have mucus plugs to keep the uterus closed off except during menstruation and right before ovulation. The uterus is anchored to the sacrum by uterosacral ligaments, to the anterior body wall by round ligaments, and it’s supported laterally by cardinal ligaments as well as the mesometrium, which is part of the broad ligament. The wall of the uterus has three layers: the perimetrium, which is a layer continuous with the lining of the peritoneal cavity, the myometrium, which is made of smooth muscle those contracts during childbirth to help push the baby out, and the endometrium, a mucosal layer, that undergoes monthly cyclic changes. The endometrium is itself made up of a single layer of simple columnar epithelium, which has ciliated and secretory cells that sit on top of connective tissue, or stroma.

There any many grooves in the stroma which is lined by the epithelium and these are the uterine glands that secrete a glycogen-rich fluid that’s essential for the developing embryo during early pregnancy. Endometrial carcinoma involves the abnormal growth of the epithelial cells that make up endometrial glands, and there are two main types. The most common is Type 1 endometrial carcinoma, which is also called endometrioid carcinoma because the tumors grow in a way that looks like normal endometrial glands. It usually involves several genetic mutations in endometrial cells, including PTEN, a tumor suppressor gene; PIK3CA, an oncogene; and ARID1A, a gene regulating chromatin structure. All of these mutations increase signaling in the PI3K/AKT pathway, which promotes the growth and replication of endometrial cells. More signaling in the PI3K/AKT pathway also enhances the expression of genes that are linked to estrogen receptors.

So having high levels of estrogen will cause the endometrium undergoes hyperplasia, leading to an increased risk of developing type 1 endometrial carcinoma? Now, excessive estrogen can come from obesity, because fat cells convert adrenal precursors into sex hormones; taking tamoxifen, a breast cancer medication that blocks estrogen receptors in the breasts, but stimulates them in the uterus; and postmenopausal estrogen therapy given without a progestin to “balance” it out. Other risk factors related to high estrogen levels are never having been pregnant; chronic anovulation, when the ovaries don’t release an egg during a menstrual cycle; and having many menstrual cycles.

Age is also a factor since endometrial carcinoma tends to develop in women who have gone through menopause, usually around 55 to 65 years of age. Finally, a hereditary condition called hereditary nonpolyposis colorectal cancer, also called Lynch syndrome, causes a high risk of developing certain cancers, including colon cancer and endometrial carcinoma. The good news is that there are actually factors that protect against Type 1 endometrial carcinoma! Taking hormonal contraceptives, being older at the time you give birth, and breastfeeding all reduce the risk of developing this type of cancer.  Now, type 2 endometrial carcinoma is rarer and has a number of subtypes. The most common subtype is serous carcinoma. The genetic mutations found most often in serous carcinoma involve the TP53 gene, another tumor suppressor, aneuploidy, or an abnormal number of chromosomes after cell division. Type 2 carcinomas don’t appear to be linked with estrogen levels. These cancers typically affect women who have endometrial atrophy and who have lower body weight. They also tend to develop later in life than Type 1 and are more common in women of African descent.  Even though there are two distinct types of endometrial carcinomas, we use the same stages to describe their development.

In stage 1, the carcinoma is only in the uterus.

In stage 2, it has spread to the cervix.

In stage 3, it has spread outside the uterus but is still within the lesser, or “true” pelvis.

This means it could affect structures like the vagina and pelvic lymph nodes.

In stage 4, it has spread beyond the pelvis.

Most Type 1 endometrial carcinomas are diagnosed in stage 1 and aren’t very aggressive, and because of that, they have a good prognosis. But type 2 carcinomas are trickier and much more aggressive and often spread to other body parts via the lymphatic system or the fallopian tubes. The main symptom of endometrial carcinoma is abnormal vaginal bleeding, usually without pain.

If it’s more advanced, there might be enlargement of the uterus if the tumor or tumors are large enough, and this can cause abdominal pain and cramping. Diagnosing endometrial carcinoma usually involves doing a transvaginal ultrasound to determine if the endometrium is abnormally thick. If it’s more than 4millimetres thick, then a biopsy or a dilation and curettage procedure is used to remove some endometrial cells and confirm the diagnosis. Surgery is the treatment for all types and stages of endometrial carcinoma. This typically means the removal of the uterus, both ovaries, and both fallopian tubes, also called a hysterectomy with bilateral salpingo-oophorectomy,  combined with the removal of pelvic and para-aortic lymph nodes. In some cases where the cancer is more advanced or is likely to spread, for example, a Type 1 carcinoma that’s stage II and above and all Type 2 carcinomas, radiation therapy and/or chemotherapy are also done after surgery.

All right, as a quick recap, endometrial carcinoma is a very common cancer of the lining of the uterus. Type 1 is associated with having abnormally high levels of estrogen over a long period of time and is usually preceded by endometrial hyperplasia. Type 2, which has several subtypes, isn’t linked with estrogen levels and is more aggressive than type 1. The most common symptom is abnormal vaginal bleeding after menopause and the treatment is hysterectomy with bilateral salpingo-oophorectomy.