CancerLinkThe uterus is the pelvic organ that holds the pregnancy and that bleeds each menstrual period. The cervix is that part of the uterus fixed at the top of the vagina. The normal size of the uterus is about that of a lemon. The uterus is divided into three parts. The great bulk of the uterus is composed of smooth muscle and forms a thick uterine wall. The inside of the uterus is lined with a glandular epithelium which is supported by the endometrial stroma. Together, the glandular lining and the stroma are referred to as the endometrium of the uterus. The endometrium is hormonally sensitive and changes throughout the menstrual cycle and during pregnancy.
Each of these three parts gives rise to cancers. The smooth muscle cancers are called leiomyosarcomas. There is also a benign tumor of smooth muscle called a leiomyoma. The common name for this benign tumor is myoma or fibroid.The stroma gives rise to a variety of cancers called sarcomas. The glandular lining gives rise to adenocarcinomas. Most, 95%, of uterine cancers are adenocarcinomas arising from the lining. The term uterine cancer usually refers to these adenocarcinomas.
Adenocarcinomas are graded. Grade I means well differentiated, that is, they are easily identified as originating from the glandular tissue and have easily identifiable glandular structures. Grade III means poorly differentiated with loss of the glandular structures. They are just solid cancer. Grade II cancers are intermediate in appearance. Grade I cancers are expected to behave the best, Grade III cancers the worst.
There are premalignant changes that can occur in the lining of the uterus. These changes are almost always due to excessive stimulation of the endometrial glands by an excess of estrogen or a prolonged estrogen influence. They can occur in younger women who do not ovulate regularly as well as in older women who are obese. These changes are called endometrial hyperplasias. They are diagnosed usually by endometrial biopsy. They are not cancers but are often best treated by hysterectomy. They can also be treated by high dose progesterone therapy. If they occur in a young woman she will probably also be relatively infertile due to irregular or infrequent ovulation. In these cases, the treatment is by drugs that cause ovulation. If you ovulate you will no longer have unopposed estrogen stimulation because you now have the progesterone phase to the menstrual cycle. If you get pregnant then that will reverse the hyperplasia also. For most women the best treatment will probably be hysterectomy.
If the woman has a problem that prevents ovulation then the ovary will continue to make estrogen. This will result in prolonged unopposed estrogen stimulation to the endometrial glands and this will increase the risk for cancer of these glands. Postmenopausal women who are taking estrogen also will have an unopposed estrogen stimulation to the uterine glands and be at increased risk for developing adenocarcinoma of the uterus. This is why a progestin such as Provera is also prescribed. Postmenopausal women who are obese have an increased level of estrogen because the adipose tissue converts other normal body chemicals into estrogen, so they are also at increased risk. Women who take Tamoxifen for breast cancer are also thought to be at increased risk because Tamoxifen is an estrogen. These increased risks are on the order of about 5-12 times the normal risk.
Conditions that increase the progesterone influence on the uterus decrease the risk for adenocarcinoma of the endometrium. Pregnancy is a time of increased progesterone levels, so women who have been pregnant most of their lives are at decreased risk. Women who have taken birth control pills for a long time are at decreased risk. Birth control pills contain both an estrogen and a progestin, but the net effect is that of the progestin. Prolonged progestin influence on the endometrium produces a thinning and atrophy of the glands which is just the opposite of the effects of estrogen. There are other minor risk factors but almost all are mediated through an estrogen progestin link.
Whatever the procedure, you must be convinced that the bleeding is not due to a cancer inside the uterus. The Pap test cannot assess the inside of the uterus and is of no value. A trial of hormones is inappropriate. Any postmenopausal bleeding must be taken seriously and evaluated. Occasionally a sonogram or ultrasound test that assesses the thickness of the endometrial lining can be helpful, especially in an elderly debilitated woman who cannot be easily biopsied and who is also an anesthetic risk. If the lining can be seen and measures less than 5mm then, there is unlikely to be a cancer present.
The problem with postmenopausal hormone replacement is that it often causes some irregular bleeding which may require a biopsy. If the hormones are taken on a cyclic basis where there are several days each month when bleeding may occur and if the bleeding is light and occurs on those days then biopsy need not be done. If it occurs at any other time in the cycle then a biopsy should be done. If the hormones are both being taken on a continuous basis each day and bleeding occurs then a biopsy should be performed.
Cancers of the uterus are staged by surgical exploration. The stages are:
| STAGING OF UTERINE CANCER | |
|---|---|
| Stage I | |
| I | Cancer limited to the lining of the uterus. |
| IA | No invasion into the smooth muscle wall. |
| IB | Invasion less than one half the thickness of the wall. |
| IC | Invasion greater than one half the thickness of the wall. |
| Stage II | |
| II | Extends into the cervix. |
| IIA | Extends only along the surface of the endocervix. |
| IIB | Extends deeper into the cervix. |
| Stage III | |
| III | Cancer has spread beyond the uterus. |
| IIIA | Cancer involves the tubes or ovaries. |
| IIIB | Metastases to the vagina. |
| IIIC | Metastases to pelvic or aortic lymph nodes. |
| Stage IV | |
| IV | Distant metastases. |
| IVA | Involves the inside of the bladder or rectum. |
| IVB | Spread throughout the abdomen or other distant organs. |
In addition, these cancers are also graded; Grade I, II and III.
To determine the correct stage the uterus, tubes and ovaries will have to be removed as well as sampling the pelvic and aortic lymph nodes. Some cases that are obviously in an advanced stage by physical examination, will not benefit from surgery and can be treated without operative staging.
Most patients will be in an early stage when diagnosed and there will be several options for treatment. Often these are elderly women who may have other medical problems. Nevertheless, a maximum effort should be taken to bring these patients to surgery since the cure rate drops by 20% if a hysterectomy is not performed. With no other gynecologic cancer is treatment so individualized as with early stage endometrial cancer.
Five year survival for each stage is:
| Stage I | 80% |
| Stage II | 65% |
| Stage III | 30% |
| Stage IV | 10% |
Stage IA, grade I, cancers have a five year survival in excess of 95%. The prognosis depends on the substage and the grade.
There are several different cell types included in the designation adenocarcinoma. Some trend to behave in a more virulent manner but all are treated about the same.
The Ca-125 blood test is often elevated in endometrial adenocarcinomas, and if so, can serve as a tumor marker.
Endometriosis is a benign condition in which endometrial tissue (glands and stroma) is misplaced onto other structures. Often there are implants on the surface of the outside of the uterus or on the lining of the pelvis. They can even occur inside the ovary. Each time the lining of the uterus bleeds during menses these implants also bleed and can cause pain and adhesions. If inside the ovary it can cause a blood filled ovarian cyst called an endometrioma. Endometriosis is a benign condition but one that can cause a lot of problems. Very rarely an endometrial adenocarcinoma can arise in an endometrial implant.
NEVER NEVER NEVER ignore postmenopausal bleeding, and do not let your doctor ignore it either.
The thick muscular wall of the uterus gives rise to the benign leiomyoma and the malignant leiomyosarcoma. The benign leiomyoma is also called a fibriod tumor. They are common and often require no treatment. They are often diagnosed by physical examination when the examiner feels an enlarged lumpy, bumpy uterus. It is only a guess that they are fibroids but usually a very good guess. An ultrasound test can also indicate a possible fibriod. Fibroids can become very large and then should be removed. Often there are multiple fibroids and occasionally these can be removed and the uterus preserved. Fibroids should diminish in size after the menopause. Therefore, any enlarged uterus in a menopausal woman not known previously to have fibroids should be removed because it could be a leiomyosarcoma. An enlarging fibroid in a premenopausal woman should also be removed. If there is no need for future pregnancies then the whole uterus should be removed.
Leiomyosarcomas are graded by the number of cells undergoing cell division. If few dividing cells are noted then it may be a low grade cancer or not a cancer at all. If a high number are noted then this will be a very aggressive cancer. Even stage I leiomyosarcomas, if high grade, will be very aggressive and most will recur. Unfortunately, there is no convincing scientific proof that either radiation or chemotherapy can prevent a recurrence from happening.
The endometrial stroma gives rise to a variety of sarcomas, some low grade and some very high grade. There are even benign conditions that can metastasize through the veins. There is no way to generalized about uterine sarcomas. Each specific type and its grade will have to be individually considered.
William M. Rich, MD
Last updated 2 July 1996