CANCER OF THE UTERUS
TYPES OF UTERINE CANCERS
RISK FACTORS FOR UTERINE ADENOCARCINOMA
SYMPTOMS
SCREENING
DIAGNOSIS
STAGING
TREATMENT
PROGNOSIS
ODDS AND ENDS
UTERINE SARCOMAS
The 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 endometrial stroma are referred to as the endometrium of the uterus. The endometrium is hormonally sensitive and changes throughout the menstrual cycle and during pregnancy.
TYPES OF UTERINE CANCERS
Each of these three parts gives rise to cancers. The smooth muscle cancers are called leiomyosarcomas(ly
o myo sarcomas). There is also a benign tumor of smooth muscle called a leiomyoma. The common name for
this benign tumor is myoma or fibroid. The endometrial stroma gives rise to a variety of cancers
classified as sarcomas. The glandular lining gives rise to adenocarcinomas. Ninety-five percent, 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.
Papillary serous adenocarcinomas and clear cell adenocarcinomas are a subtype of uterine adenocarcinomas.
They are different because of their increased potential to spread throughout the abdomen. In this they
sometimes behave like an ovarian cancer. The diagnosis and staging is the same as for the more usual
endometrial cancer. The best treatment has yet to be demonstrated. There is a good reason to consider
treating the entire abdomen, but there is no good way to do it. Whole abdominal radiation can be done,
but it can have a lot of side effects. This is a situation where several opinions should be obtained.
RISK FACTORS FOR UTERINE ADENOCARCINOMA
Age is the most important risk factor. This is a cancer of postmenopausal and perimenopausal women. There
is also a well-recognized association with estrogen. Estrogen is a hormone produced by the ovary. The
ovary does several things under the direction of the pituitary gland in the head. First, the pituitary
directs the ovary to start maturing an egg. It does this by sending the ovary the pituitary hormone
Follicle Stimulating Hormone (FSH). The ovary develops a small cyst or follicle about one half inch in
size within which is the egg. During the maturation process the ovary is making estrogen. One of the
effects of the estrogen is to stimulate the endometrial glands to grow and proliferate. Then the
pituitary tells the ovary to ovulate which means break the follicle and release the egg. The pituitary
hormone for this is called Luteinizing Hormone (LH).
The egg is ejected and floats into the fallopian tube. The remnant of the follicle, under the influence
of LH starts to make progesterone. Progesterone converts the lining of the uterus to accept the
pregnancy. If pregnancy does not occur that cycle then the ovary stops making progesterone. When the
progesterone level falls the support for the uterine lining is lost and it falls off. This is the
menstrual period. Then, it all starts over again: estrogen, ovulation, progesterone, and the period.
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 an
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.
SYMPTOMS OF UTERINE CANCER
The most frequent symptom of cancer of the uterus is abnormal bleeding. In postmenopausal women any
bleeding is considered cancer of the uterus until proven not to be. The only way to prove that there is
or is not a cancer inside the uterus is by removing some of the uterine lining as a biopsy. This can
often be done easily in the office without any anesthesia, or it can be done in the operating room with
an anesthetic. The procedure is called a D&C, dilatation of the cervix and curettage of the uterine
lining. Sometimes a scope can be inserted through the cervix into the uterus and the lining visualized
and biopsied directly. This is called hysteroscopy.
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
SCREENING FOR UTERINE CANCER
There are no recommendations for screening for cancers of the uterus. The only screening procedure is an
endometrial biopsy. Some have suggested that women who are taking replacement estrogen only, without the
progesterone, should have an annual biopsy. Also women on Tamoxifen should probably be biopsied annually.
The Pap test is inadequate for cancers inside the uterus although occasionally this cancer will be found
on a Pap test. If the Pap test shows endometrial cells then this is abnormal and should be evaluated with
an endometrial biopsy.
SURGICAL STAGES OF CANCER OF THE UTERUS Stage I Cancer limited to the lining of the uterus IA No invasion into the uterine wall IB Invasion into less than one half of the uterine wall IC Invasion into more than one half the uterine wall Stage II Extends into the cervix IIA Extends only superficially along the endocervix IIB Extends deep into the cervix Stage III Cancer has spread beyond the uterus IIIA Cancer involves the tubes or ovaries IIIB Spread to the vagina IIIC Spread to the pelvic or aortic lymph nodes Stage IV Distant metastases IVA Is inside the bladder or rectum IVB Throughout the abdomen or other distant sites |
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. An early stage is assigned by excluding the more advanced stage. Some cases that are obviously in an advanced stage by physical examination will not benefit from surgery and can be treated without operative staging.
FIVE YEAR SURVIVAL FOR UTERINE ADENOCARCINOMA 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.
ODDS AND ENDS
Adenocarcinomas of the endometrium are often hormonally sensitive cancers and occasionally estrogen and
progesterone receptors will be determined, but this is not commonly done.
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 IGNORE POSTMENOPAUSAL BLEEDING, AND DO NOT LET YOUR DOCTOR IGNORE IT EITHER. YOU MUST PROVE
THAT IT IS NOT DUE TO A UTERINE CANCER.
UTERINE SARCOMAS
Uterine sarcomas are rare cancers and are not easy to generalize. There are several types each with
several gradations from low grade to high grade malignancies. There is no standard treatment. Each case
must be managed separately.
The thick muscular wall of the uterus gives rise to the benign leiomyoma and the malignant
leiomyosarcoma. The benign leiomyoma is also called a fibroid 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 fibroid. 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 postmenopausal 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 ,i.e. a high
mitotic count, 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 generalize
about uterine sarcomas. Each specific type and its grade will have to be individually considered.
William M. Rich, M.D.
Clinical Professor of Obstetrics and Gynecology
University of California, San Francisco
Director of Gynecologic Oncology
University Medical Center
Fresno, California