Uterine Cancers

There are two basic types of uterine cancers.

The first and much more common type is cancer of the uterine lining, or endometrial cancer, a type of adenocarcinoma. Endometrial cancers typically cause abnormal uterine bleeding. This is the primary reason that doctors are quick to perform an endometrial biopsy to exclude the possibility of endometrial cancer when women have bleeding between periods or postmenopausal bleeding. The risk of endometrial cancer increases with increasing age and for women after menopause.

There are other risk factors for endometrial cancer, as well. Risk of endometrial cancer is increased in women who are obese and do not ovulate regularly, women who have high blood pressure or diabetes, and women who have never had a child. Each of these conditions is thought to result in an excess of estrogen, which causes the endometrial lining to grow. This is why estrogen alone is seldom given to a woman with a uterus; it is usually combined with progesterone or a progestin to limit the growth of the lining. Additionally, physicians are much more likely to do a biopsy in women who have any of these risk factors than in women who have none but who have some irregular bleeding.

The rarer type of cancer is a cancer of the muscle, or a sarcoma. There are many different kinds of sarcomas, such as carcinosarcoma, leiomyosarcoma and endometrial stromal sarcoma. Each different type of sarcoma has a distinct tissue pattern when viewed under the microscope; by examining this pattern we both determine the kind of sarcoma and get a sense of how it will behave. In the future, as with other cancers, we will not depend on the microscopic pattern but will instead look for specific molecular markers (molecules made by the tumors that identify them and tell us how aggressively they will behave and how to best treat them). Sarcomas are the kind of cancer that is often confused with fibroids, since both diseases can be felt as a nodule in the wall of the uterus.

To be 100 percent certain that a woman has a fibroid and not a sarcoma, the tumor must be removed and examined under a microscope. This is generally not a wise way to proceed, however. A woman who is suspected to have fibroids has a risk of having a uterine sarcoma that is at most 1 in 10,000, but the risk of a significant complica-tion during surgery is 1 in 1,000. Therefore, for most women, the risk of having an iatrogenic complication (one caused by the procedure) outweighs the chance of finding a cancer. For this reason the American College of Obstetricians and Gynecologists recommends that concern about cancer should not be the only reason to proceed with a hysterectomy for a woman with uterine fibroids. Rarely cancers will be missed with this strategy, but many women will be spared significant complications from surgery.

Although it is possible to stick a needle into many fibroids and obtain a small piece of tissue to view under a microscope, this, too, is generally not a wise way to proceed for most women. Distinguishing between a sarcoma and a fibroid involves looking at many different criteria in a number of different areas of the tumor, including:

  • the number of dividing cells over many different areas of the tumor (mitoses per high power field of magnification)
  • the appearance of the cells (atypia)
  • the extent and the pattern of dead cells (necrosis).

Distinguishing between a sarcoma and a fibroid is so difficult that there are tumors that don’t fit into either category and that are classified as leiomyomas of uncertain malignant potential (UMP). Because pathologists need to look at many different areas to be certain that the tumor is a sarcoma, a frozen section diagnosis (one obtained by quickly freezing tissue and examining it while the surgery is going on) is not as reliable as with other tumors, so doctors are not certain of the diagnosis until the full report is ready several days later. It can be a frustrating wait for a woman and her family, but it is important to have the correct information.  

Most medical textbooks teach that rapid growth of a uterine mass should make the physician suspect that it is a sarcoma rather than a fibroid. Not only is there no agreement on what amount of growth is too much, but there is no evidence that rapid growth is associated with sarcomas. Many fibroids can grow rapidly, and unnecessary surgeries are sometimes performed because of concern regarding growth.

For a woman who has specific factors that increase the risk of sar-coma, surgery may be justified. The risk of sarcomas increases with increasing age, regardless of menopause status. Thus an 80-year-old woman with a uterine mass may be more likely to have a sarcoma than a 65-year-old woman with a uterine mass, even though both women are in menopause. Therefore, a woman who develops a new uterine mass after menopause, particularly after some time in the postmenopausal period, is more likely to make the physician suspect a diagnosis of a sarcoma than a younger woman, who is more likely to have fibroids.

Some women who may have had silent or asymptomatic fibroids have their first ultrasound near the time of menopause and may mistakenly be thought to have a new, suspicious uterine mass. Waiting and watching is a reasonable decision in this case, rather than deciding to have immediate surgery. If the mass stays the same size or shrinks over time, it is most likely a fibroid. If it grows, further diagnostic imaging or treatment may be the best course.

Black women appear to be more likely to have sarcomas than white women, just as they are more likely to have fibroids. Besides race, other risk factors for uterine sarcomas include prior radiation therapy of the pelvis (in which the uterus would have been exposed to radiation) and use of tamoxifen. As discussed previously, women who have the rare genetic syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC) appear to be at risk for a sarcoma, which may develop at an early age. A physician will be more likely to suspect a sarcoma if he or she feels a uterine mass on pelvic exam in a 62-year-old black woman who has previously been treated with tamoxifen for breast cancer than in a 35-year-old woman without these additional risk factors. This increased suspicion may lead to more or different diagnostic testing (such as ordering magnetic resonance imaging, or MRI, rather than an ultrasound as the first test) or a lower threshold for considering surgical treatment. 

There are a few tests that may increase your physician’s suspicion that you have cancer rather than a fibroid. In a series of women with sarcomas treated at the same institution, the cancer diagnosis of about a third of them had been made before surgery with an endometrial biopsy. Although a normal biopsy does not eliminate the possibility of cancer, since it is a safe and easy test to perform, for most women it makes sense to have a biopsy before surgery for a presumed sarcoma.

MRI can also be useful in differentiating a sarcoma from a benign uterine leiomyoma. Again, a normal MRI does not exclude the possibility of cancer, but particular patterns will alert your physician to an increased possibility of a cancer. Finally, scientists are looking at serum markers (proteins in the blood that indicate the disease, in this case a sarcoma, is present) to help distinguish fibroids from sarcomas. Currently these are done only as research studies, but they may be useful in the future.

Some reports suggest that sarcomas are less likely than fibroids to respond to conservative therapies such as gonadotropin-releasing hor-mone (GnRH) agonist and uterine artery embolization. Therefore, if you don’t respond to one of these minimally invasive therapies, you have to think carefully about whether there are benefits to having a hysterectomy for definitive treatment and diagnosis. All these tests provide clues rather than absolute proof of the presence or absence of a sarcoma. Even a mass that grows rapidly in a post-menopausal woman may turn out to be a fibroid. Alternatively, a sarcoma can be present in a young woman with no risk factors.

If you are having surgery for a suspected sarcoma, most doctors recommend that the ovaries should be removed as well, because some sarcomas respond to the steroid hormones estrogen and progesterone, produced by the ovaries. Your surgical plan should take this factor into consideration.

Finally, in the past, it was argued that fibroids should be removed when they reach a specified size so that an ovarian cancer would not be missed. This is the same reason that an ultrasound examination should be done if fibroids are suspected on the basis of a pelvic exam: the lumpy, irregular feel of a fibroid uterus can be confused with a mass in the ovaries. The clarity of ultrasound imaging has increased substantially over the past two decades, however, so it should not be necessary to have surgery to eliminate the possibility of an ovarian mass.

The more common problem is that the ovaries may not be seen on an ultrasound in the presence of large fibroids. Fibroids and ovaries look very different on ultrasound, but the fibroids may be pushing the ovaries into an atypical position so that they are hard to see. Because ovarian cancers generally cause the ovaries to be larger than normal ovaries, not seeing the ovaries is usually a reassuring sign, but, again, there is never a guarantee.

In the twenty-first century surgeons seldom remove organs to prevent them from becoming cancerous. We have even moved away from routinely taking out the appendix when a person is undergoing unrelated abdominal surgery, unless there is a specific reason to do so. The exception to this rule is when a specific problem such as a genetic mutation (such as BRCA1 or BRCA2) substantially increases the risk of disease (breast and ovarian cancer). Even in this case, some women choose to have their ovaries (prophylactic oophorectomy) and/or breasts (prophylactic mastectomy) removed, and other women do not. Women make their choices based on many factors, including their experience with family members with these cancers, concerns about the disfigurement of surgery, and their work and family situations. Because you will have to accept the consequences of your decision, you need to participate in the decision-making process.

Having HLRCC syndrome is the only analogous situation we have with fibroids. Women who have the fumarate hydratase (FH) mutation causing this syndrome appear to have an increased risk of forming a sarcoma. Unfortunately, because we have only recently recognized this syndrome, we have little information to offer women as a guide in their decision-making process. We don’t know whether the risk of cancer is increased 10 percent or 50 percent or 90 percent. Even in this case, each woman needs to make her own decisions. However, for the woman who has symptoms from her fibroids and who has decided on treatment, knowing this additional information about her genetic makeup may help tip the balance toward hysterectomy. The weighing of risks and benefits here is similar to that for the woman with symptomatic fibroids and problems with human papilloma virus (HPV) and abnormal Pap smears. For her situation, a hysterectomy solves two problems, whereas a myomectomy only solves one.

No one should be scared into having a hysterectomy. If your doctor says you need a hysterectomy because the fibroids “could be cancerous,” review the information you have. Do you have risk factors? Is anything suspicious in the imaging? Does the MRI report state “highly suspicious for a sarcoma” or only “cannot exclude a sarcoma”? Does your doctor or does your hospital see a high volume of women with similar situations? If you have any questions, seeking a second opinion can be a good idea. Most large hospitals can arrange an appointment with a specialist right away so that a woman suspected of having cancer doesn’t have a long wait for an appointment.