The author reports no financial relationships relevant to this article.
CASE 1 Rapid growth=cancer?
Mrs. G., 47 years old, has had uterine fibroids the size of a 12-week pregnancy for about 6 years. At today’s examination, however, her uterus feels about the size of a 16-week pregnancy.
She is aware that her abdomen is bigger, and she complains of some abdominal pressure and urinary frequency. She reports no abnormal bleeding and no abdominal pain.
Mrs. G. is upset because another physician told her she might have cancer and needs a hysterectomy immediately. She tells you that she does not want a hysterectomy unless “it’s absolutely necessary.”
Ultrasonography at this visit reveals that two of the three fibroids noted on a previous sonogram have grown—one from 6 cm to 9 cm in diameter; the other from 5 cm to 8 cm.
What do you tell Mrs. G.?
Uterine fibroids, also called myomas, are benign, monoclonal tumors of the myometrium that contain collagen, fibronectin, and proteoglycan. The collagen fibrils are abnormally formed and in disarray; they look like the collagen found in keloids.1 Although the precise causes of fibroids are unknown, hormonal, genetic, and growth factors appear to be involved in their development and growth.2,3
About 40% of fibroids are chromosomally abnormal; the remaining 60% may have undetected mutations. More than 100 genes have been found to be up-regulated or down-regulated in fibroid cells. Many of these genes appear to regulate cell growth, differentiation, proliferation, and mitogenesis.
- A myoma is benign tumor of the myometrium
- In a premenopausal woman, rapid uterine growth almost never indicates the presence of uterine sarcoma
- In an older woman who experiences uterine growth, abdominal pain, and irregular vaginal bleeding, pelvic malignancy may be suspected; an increased level of LDH isoenzyme 3 with increased gadolinium uptake on MRI within 40 to 60 seconds suggests a diagnosis of leiomyosarcoma
- Most fibroids have no impact on fertility, but submucosal fibroids that distort the uterine cavity decrease fertility; removing them increases fertility
- Location, size, number, and extent of myoma penetration into the myometrium can be evaluated by pelvic MRI, with coronal, axial, and sagittal images without gadolinium contrast
- Given the risks associated with surgery and the lack of proof of efficacy, myomectomy to improve fertility should be undertaken with caution
- Most myomas do not grow during pregnancy. Unfavorable pregnancy outcomes are very rare in women with myomas.
- Oral contraceptives and postmenopausal hormone therapy almost never influence fibroid growth. Women with fibroids can usually use these therapies safely.
Differentiating benign myoma from uterine sarcoma
Myomas have chromosomal rearrangements similar to other benign lesions, whereas leiomyosarcomas are undifferentiated and have complex chromosomal rearrangements not seen in myomas.4 Genetic differences between myomas and leiomyosarcomas indicate they most likely have distinct origins, and that leiomyosarcomas do not result from malignant degeneration of myomas.2
In premenopausal women, rapid uterine growth almost never indicates uterine sarcoma: One study found only one sarcoma among 371 (0.26%) women operated on for rapid growth of a presumed myoma, and no sarcomas were found in the 198 women who had a 6-week-pregnancy-equivalent increase in uterine size over 1 year.5
Clinical indications. The clinical signs that would lead to suspicion of pelvic malignancy are:
- older age
- abdominal pain
- irregular vaginal bleeding.6
The average age of 2,098 women with uterine sarcoma reported in the SEER (Surveillance Epidemiology and End Results) cancer database from 1989 to 1999 was 63 years, whereas a review of the literature found a mean age of 36 years in women subjected to myomectomy who did not have sarcoma.3,7
Diagnostic tests. The distinction between benign myoma and leiomyosarcoma need not be based on clinical signs alone. Preoperative diagnosis of leiomyosarcoma may be possible, using laboratory values of total serum lactate dehydrogenase (LDH) and LDH isoenzyme 3 plus gadolinium-enhanced magnetic resonance imaging (MRI) scan (Gd-DTPA), with initial images taken 40 to 60 seconds after injection of gadolinium. A study of 87 women with fibroids, 10 women with leiomyosarcoma, and 130 women with degenerating fibroids reported 100% specificity, 100% positive predictive value, 100% negative predictive value, and 100% diagnostic accuracy for leiomyosarcoma with this combination diagnostic procedure.8