Table I. Cystic degeneration of a leiomyoma mimicking other diagnoses2,3,4
The majority of women with uterine leiomyomas are asymptomatic; they become symptomatic in approximately 25% of cases5. Symptomatic leiomyomas are among the most common reasons for hysterectomy in the United States6.
Leiomyomas are spherical or ovoid in shape and have a whirled appearance on cut surface. Large leiomyomas may outgrow their limited blood supply; resulting in hyaline or cystic degeneration. As the blood supply to a leiomyoma decreases, it may become calcified.
Estrogen and progesterone receptors are in higher concentrations in leiomyomas than in the normal surrounding myometrium7. The growth rate of leiomyomas is related to their number of estrogen and progesterone receptors8. Gonoadotrophic-releasing hormone agonists result in a temporary reduction in the size of leiomyomas by 45% at 24 weeks of treatment. However, once the medication is discontinued, the leiomyomas return to their former size in 6 months9.
Signs and Symptoms
The location, number and size of leiomyomas determine when, and how, they become symptomatic. Abnormal uterine bleeding, pelvic pressure, and lower abdominal pain are the most common complaints of women with symptomatic leiomyomas. If the leiomyomas are large enough (Fig. 2), obstructive hydronephrosis may occur.
Leiomyomas may occur in either the cervix or the main body of the uterus. Cervical leiomyomas more commonly involve the posterior wall. Within the corpus of the uterus, a leiomyoma is either subserosal (Fig. 3), intramural, submucosal (Fig. 4) or intracavitary (Fig. 5). A pedunculated leiomyoma (Fig. 6) is connected to the uterus by a stalk containing its vascular supply. Intraligamentary tumors extend into the broad ligament. Occasionally, a pedunculated leiomyoma will become attached to the omentum. As the blood supply from the omentum increases, the blood supply from the uterus decreases. Eventually, the leiomyoma will become parasitic – deriving all if its blood flow from the omentum.
Because of their location, submucous leiomyomas are the most symptomatic and, may result in significant vaginal bleeding. These leiomyomas may also become pedunculated, extending into the endometrial cavity and even through the cervix.
Leiomyomas only rarely appear to affect fertility10.
The main vessel supplying a leiomyoma is on its periphery and can be visualized with color Doppler (Fig. 7). This vessel is detected in approximately half of uterine leiomyomas and has been associated with an increased likelihood of leiomyoma growth11. In contrast to the single feeding vessel of a polyp, submucosal leiomyomas generally have several central vessels12.
13% of premenopausal women with leiomyomas will develop one or more additional leiomyomas over 2.6 years. Some leiomyomas with a mean diameter of 1.1 cm or less may completely resolve13.
Multiple discrete shadows tend to originate from within larger leiomyomas (> 5 cm). This sonographic pattern is derived from the transition between muscular and fibrous tissue within the leiomyoma. Since this sonographic finding is dependent upon the muscular and fibrous components of the leiomyoma, it is not present with all leiomyomas. This pattern may also be present with ovarian fibromas and adenomyosis14.
A lipoleiomyoma contains a high concentration of fat (Fig. 8), while a vascular leiomyoma has numerous large vessels.
Treatment options for women with symptomatic leiomyomas have expanded considerably. In the past, hysterectomy was the treatment of choice. Myomectomy and endometrial ablation are additional surgical options. Uterine volume continues to gradually decline over 6 months after myomectomy. The removal of the leiomyoma and its higher estrogen concentration results in a gradual reduction in the size of the hypertrophied surrounding myometrium. Regardless of the initial size of a myomatus uterus, the non-myoma volume ends up very close to the volume of a normal uterus15,16.
Medical therapy has been limited to the temporizing utilization of GnRH agonists to reduce the size of leiomyomas prior to surgical intervention.
Over the past 10 years interventional therapy, i.e. uterine artery embolization has gained in popularity17. In one study the mean reduction in vascularity after uterine artery embolization was 44%. The size of leiomyomas may gradually decrease in size for up to 1 year after embolization18. Collateral blood flow from the ovarian artery will reduce the efficacy of uterine artery embolization19.
The location of leiomymomas correlates with outcome – a submucosal location is a strong predictor of successful uterine fibroid embolization20.
Pedunculated intracavitary or subserosal leiomyomas are removed by hysteroscopy and laparoscopy, respectively. Uterine artery embolization is reserved for those leiomyomas with a larger intramural component16.
Although women who are considering pregnancy have been excluded from studies utilizing uterine artery embolization, successful pregnancies after this procedure have been reported16.
The complications reported with uterine artery embolization are outlined in Table IV. Death has been reported in 4 of 50,000 reported procedures21.
Table IV. Complications associated with uterine artery embolization18
- Postembolization syndrome
- Abdominal pain
- Groin infection
- Arterial thrombosis
- Allergic reaction to contrast
- Non-targeted ovarian embolization
- Deep vein thrombosis
- Pulmonary embolism
Clinical failure rates after uterine artery embolization are between 6% and 19%15.
Thermoablation of uterine leiomyomas utilizing MRI-guided focused ultrasound has recently been employed. Pre-treatment with a GnRH agonist not only decreases the size of leiomyomas, but also reduces their blood supply. The latter effect enhances thermoablation by reducing heat conduction22.
As the treatment options for uterine leiomyomas has increased, so has the importance of pretreatment assessment. Sonohysterography (Fig. 9) has become an important addition to transvaginal sonography in the accurate delineation of submucous and intracavitary leiomyomas.23
Submucous leiomyomas have been classified based upon the extent of uterine wall invasion (Table II). Cohen and Valle24 have proposed a similar classification for intramural and subserosal leiomyomas (Table III).
Table II. Classification of submucous leiomyomas25
O: intracavitary, pedunculated leiomyomas
I: submucous leiomyomas extending < 50% into the myometrium
II: submucous leiomyomas extending > 50% into the myometrium
Table III. Classification of intramural and subserosal leiomyomas23
O: pedunculated subserosal leiomyoma
I: involvement of < 50% of the outer uterine wall
II: involvement of > 50% of the myometrial wall
III: leiomyomas that extend from the mucosa to the serosa
The utilization of these classifications for pre-operative mapping of leiomyomas allows the selection of the most appropriate operative technique. As a submucosal leiomyoma extends further into the myometrium, the likelihood of complete resection is reduced and the number of repeat procedures to affect complete removal increases25. As the size of the uterus and the number of leiomyomas increases, transvaginal sonography even with sonohysterography is increasingly limited in its ability to accurately map all of the patient’s leiomyomas. MRI18 and, more recently, 3D ultrasound (Fig. 10) has, therefore, been employed.
Adenomyosis is characterized by the endometrial invasion of the myometrium. In addition, there is a generalized hypertrophy and hyperplasia of the surrounding muscular elements of the myometrium26,27. Its prevalence in surgical series varies between 5% and 70%28 with a mean of 20% - 30%29. The histologic criteria that are used, as well as the number of myometrial sites sampled, play a role in the discrepancies in the reported prevalence29.
Adenomyosis has two distinct forms: nodular and diffuse. The nodular type is circumscribed and may be confused with a leiomyoma. An adenomyoma, in contrast to a leiomyoma, does not have distinct margins and contains one to several cystic spaces. In the diffuse form the islands of adenomyosis are dispersed throughout the myometrium. The presence of estrogen and progesterone receptors in adenomyotic lesions indicates that it is hormone dependent27. Bazot et al27 have graded adenomyosis 1, 2 and 3 based on the involvement of the inner third of the myometrium, two-thirds of the myometrium, and the entire myometrium, respectively. There is not a consistent diagnosis of the depth of endometrial penetration that is required to diagnose adenomyosis. Most authors use a depth of endometrial penetration between 1-4 mm30. McCausland31 has reported that 1 mm of endometrial penetration with smooth muscle hypertrophy is sufficient to cause menorrhagia.
Adenomyosis may result in menorrhagia and/or dysmenorrhea. There is a correlation between the depth of adenomyosis and the severity of menorrhagia31. It has been hypothesized that the dysfunctional generalized hypertrophy surrounding the endometrial glands prevents uterine contractions from tamponading bleeding myometrial arterioles32. The posterior uterine wall is more frequently involved with adenomyosis31.
Since adenomyomas extend into the normal myometrium, excision is difficult. As with the diffuse form, hysterectomy remains the primary treatment.
Transvaginal ultrasound has been reported to diagnosis adenomyosis with a sensitivity, specificity, positive and negative predictive value of 87%, 98%, 74.1% and 98.6%, respectively33. Transabdominal sonography alone cannot be used to accurately diagnosis adenomyosis27. However, in women with large uteri, transvaginal sonography cannot adequately evaluate the entire uterus. In these cases combined transabdominal and transvaginal sonography are required to accurately diagnosis adenomyosis27.
The sonographic criteria for adenomyosis are outlined in Table V26. The number and distribution of myometrial cysts (Fig. 11) correlates with the grade of adenomyosis27. Histologically these cysts are ectopic endometrial glands. Since adenomyosis may consist of a basal glandular component that is not responsive to hormones, cyclic hemorrhage rarely occurs in adenomyosis. Cystic degeneration of small leiomyomas may mimic the lacunae associated with adenomyosis34. Hypoechoic linear myometrial striations are due to the myometrial hypertrophy associated with the hormonal status of the ectopic myometrial glands27. The latter finding is, therefore, more prevalent in menstruating, in contrast to post-menopausal women. A poor definition of the endo-myometrial junction and the lack of a mass effect on the myometrium suggests the presence of diffuse adenomyosis33. Occasionally, hyperechoic myometrial nodules will be present (Fig. 12).
Table V. Sonographic criteria for adenomyosis26,34,35
- Globular shaped uterus
- Myometrial cysts (2-6 mm in diameter)
- Mottled inhomogeneous myometrium
- Indistinct borders to a myometrial mass
- Indistinct endometrial stripe
- Hyperechoic myometrial nodules
- Asymmetric thickening of the anterior or posterior uterine wall
- Mimimal mass effect on the endometrium or serosa
With significant adenomyosis the uterus is globular and the diameter of the anterior and posterior myometrium are asymmetric. Hypoechoic myometrial contractions can occasionally be mistaken for adenomyosis. Within 10 to 15 minutes the latter will resolve35.
Color Doppler can be utilized to help distinguish between leiomyomas and adenomyosis. While larger leiomyomas tend to have a peripheral feeding vessel, adenomyosis has either no vascular flow or vessels transversing the hypertrophic myometrium between cystic spaces27.
The accuracy of transvaginal ultrasound in the detection of adenomyosis is highly operator dependent. An increased awareness of adenomyosis as a possible diagnosis in conjunction with sufficient clinical experience are required in order to detect the relatively subtle sonographic signs of adenomyosis. In women without leiomyomas, transvaginal sonography is as reliable as MRI (Fig. 13) in the detection of adenomyosis. However, in the presence of multiple leiomyomas, MRI performs better in detecting concomitant adenomyosis36.
A myometrial biopsy at the time of hysteroscopy has been suggested as another method to diagnosis adenomyosis31. However, this technique has not been found to improve the diagnostic accuracy of transvaginal sonography37.
Conservative surgery consists of endomyometrial ablation for patients with disease limited to the endo-myometrial junction (i.e. a depth of 2-3 mm). This procedure results in a 55% relief of menstrual symptoms for at least 2 years38. For patients with deeper adenomyosis, endometrial ablation is not successful32. In fact, incomplete ablation of the endometrium may initiate the growth of the endometrium into the myometrium resulting in adenomyosis32.
The primary treatment of adenomyosis remains hysterectomy. There have been limited attempts to utilize uterine artery embolization in cases of isolated adenomyosis without concomitant leiomyomas. Pelage et al30 reported that after 6 months 15/16 (94%) of women with symptomatic adenomyosis reported improvement in menorrhagia after uterine artery embolizaton. However, improvement decreased over time with only 5/9 (56%) reporting resolution of menorrhagia at 2 years.
While anti-estrogen drug therapy has been attempted, there is a lack of controlled studies. As a result the efficacy of anti-estrogens (birth control pills, progestogens, GnRH agonists) has not yet been conclusively proven38.
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