Obstetrics & Gynecology

Daniela Contage Siccardi, MD

Leiomyomas



Uterine leiomyomas are benign tumors composed of smooth muscle and fibrous connective tissue. They are also referred to as fibromyomas, fibromas, fibroleiomyomas, fibroids or simply myomas. They may occur singly but often are multiple, with variations in size and are more common in African-American than in white women.

Etiology

It's believed that myomas are monoclonal tumors resulting from somatic mutations of one single neoplastic cell.

Factors affecting tumor growth- Despite a genetic predisposition, estrogens, progesterone and HGH(human growth hormone) play an important role in the regulation of the tumor growth.

1-Estrogen

Its influence is based on clinical evidence such as:

a)myomas generally appear during menacme;
b)there is often a rapid growth of myomas during pregnancy and exogenous estrogen therapy;
c)there is often a reduction of such tumors during menopause;
d)there is an association with other processes estrogen-dependent like endometriosis(50%), fibrocystic changes of the breast(14.8%), adenomyosis(16.5%) and endometrial hyperplasia(9.3%) - (McElin & Bird)
e)17B hidroxydesidrogenase: this enzyme transforms estradiol(a “strong” estrogen) into estrona(a “weak” estrogen). The activity of this enzyme is reduced in myomatous tissue, which has also more receptors for estrogen than normal myometrium.

2-Progesterone

Progesterone is the natural antagonist of estrogen. It acts inhibiting tumor growth by two manners: activating 17B hidroxydesidrogenase and reducing the number of estrogen receptors in the tumor.

3-HGH

HGH levels are reduced during pregnancy, but a hormone with similar structure and biological activity -HPL- appears in this period, suggesting that the rapid growth of leiomyomas during pregnancy may be a result of a sinergistic action between HPL and estrogen. (Buttram & Reiter).

Classification

Classification of myomas can be based on: location and uterine layer affected.(Figure1)

1-Location

a)cervical(2.6%)- generally grows toward vagina, causing sinusiorragia and infection.

b)isthmic(7.2%)- more frequently causes pain and urinary problems.

c)corporal(91.2%)- this is the most common location,and frequently causes no symptoms.

2-Uterine Layer

1-Subserous- located just beneath the serosal surface. They grow out toward the peritoneal cavity,and can be sessile or pedunculated. The pedunculated ones may attach themselves to adjacent structures like the bowel, omentum or mesentery, and develop a secondary blood supply, loosing its primary uterine blood supply - parasitic leiomyoma. Subserous myomas may also extend into the broad ligament- intraligametary leiomyomas.

2-Submucous - located beneath the endometrium. They can be sessile or pedunculated. The pedunculated myomas can protrude to or through the cervical canal, and on these cases they are more subject to torsion or infection. Submucous fibroids are often associated with an abnormality of the endometrium, resulting in a disturbed bleeding pattern.

3-Intramural- these are the most common, occurring within the walls or the uterus.

Pathology

Gross Pathology - Leiomyomas are well circumscribed tumors, separated from the myometrium by a pseudocapsule of connective tissue.The consistency varies from hard and stony to soft.

Microscopic Pathology -The microscopic pattern is of groups and bundles of smooth muscle fibers intermixed with fibrous connective tissue and arranged in a whorled fashion. Mitoses are rare.

Degenerative Changes

Degenerative changes are reported in approximately two-thirds of all specimens, but most of them have no clinical significance. They occur secondary to postmenopausal atrophy, infection, alterations in circulation or malignant transformation.

1-Hyaline degeneration- It is the most common degenerative change.

2-Cystic degeneration- Liquefaction follows extreme hyaline degeneration. It can be eventually a sequel of necrosis.

3-Mucoid degeneration- Hyaline areas are replaced by a soft, gelatinous material. It occurs usually in large tumors, with impaired arterial input.

4-Fatty degeneration- Lipids are found inside smooth muscle fibers.

5-Carneous degeneration-It occurs most frequently in pregnancy, and is believed to be caused by asseptic degeneration and infarction associated with local hemolysis. The process is usually accompanied by pain, but is self-limited. Rare complications include: preterm labor, tumor rupture with peritoneal bleeding, shock and even initiation of disseminated intravascular coagulation.

6-Calcification- It can occur after necrosis, fatty degeneration and in the postmenopausal patient. Precipitation of calcium carbonate and phosphate will most frequently occur in areas with circulatory deprivation.

7-Sarcomatous degeneration(malignant transformation)-It occurs in less than 1% of leiomyomas. Controversy exists whether this represents a true degenerative change or a spontaneous neoplasm. Leiomyosarcoma is a rare malignant neoplasm composed of cells that have smooth muscle differentiation, with a count of 10 mitotic figures per 10 high-power-fields(hpf).

Clinical Manifestations

Most women with leiomyomas are asymptomatic. Symptoms occur only in 35-50% of affected patients.

1-Abnormal uterine bleeding- It is the most commom symptom(30%). The typical bleeding pattern is menorrhagia,but metrorragia, hypermenorrhea, or any type of abnormal bleeding is possible. The abnormal bleeding commonly produces iron anemia.

Fisiopathology:- The abnormal uterine bleeding may be explained by: an increase in the surface area of the endometrial cavity;

-disturbance in the hemostatic contraction of muscle bundles;

-distortion and congestion of the surrounding vessels;

-ulceration of the overlying endometrium.

2-Pain- Acute pain is usually associated with torsion of a pedunculated myoma or infarction progressing to carneous degenerartion. The most common pattern, however, is a feeling of pelvic heaviness that can radiate to the back or lower extremities. Pain may also be characterized as dysmenorrhea or dyspareunia.

3-Infertility- Myomas are a rare cause of infertility. Large intramural tumors located in the cornual regions may obstruct the tubes. Continuous bleeding in patients with submucous leiomyomas may impede implantation. There are increased incidences of abortion and premature labor in patients with intramural or submucous tumors.

4-Urinary Symptoms-Urinary frequency, urinary retention, ureteral obstruction and hydronephrosis.

5-Intestinal Symptoms- Constipation and intestinal obstruction.

6-Venous Congestion- Caused by compression of large tumors leading to: varicosities, lower extremity edema, hemorrhoids, pain and dyspareunia.

7-Malignant Transformation- It must always be suspected when the following signs are present: enlargement of the uterus in postmenopausal patients, rapid changes in size and consistency of the tumor, ascite and recurrence after surgery.

Diagnosis

Diagnosis can be made with confidence in 90% of the patients on the basis of a good history and physical examination.

Laboratory Findings

1-Hemoglobin/Hematocrit- to assess the degree of blood loss and adequacy of replacement.

2-Coagulation Profile- must be ordered when a history of a bleeding diathesis is suggested.

Imaging Studies

Pelvic ultrasonography is helpful to assess uterine dimension, myoma location,endometrial thickness and adnexal anatomy. Transvaginal scanning is preferred to abdominal scanning.

Endometrial Sampling

It must be performed to evaluate abnormal bleeding in patients who are at risk for endometrial polyps, hyperplasia, or carcinoma. The technique of D&C has been replaced largely by the office endometrial biopsy. Indication for a D&C or hysteroscopy include: patient intolerance of endometrial biopsy,anatomic factors(eg:obesity), cervical stenosis and abnormal bleeding in a patient with another surgical procedure performed under general anesthesia.

Differential Diagnosis

Any pelvic mass, specially during reproductive years and menopause. Differential diagnosis include: ovarian cysts or tumors, tubo-ovarian abscesses, pregnancy, adenomyosis,endometrium cancer, myometrial hypertrophy or congenital anomalies.

Treatment

The treatment of myomas must be adapted to each woman, and includes surgical and nonsurgical options.

1-Nonsurgical

a)Expectant Management- In the absence of symptoms or large myomas, observation with periodic examination (every 3 to 6 months) is appropriate. After assurance of slow growth or stable uterine size, annual follow-up may be appropriate.

b)Drugs- They can be used in order to reduce bleeding and to reduce or stable the tumor size. Theoretically, every drug that reduces estrogen production or its effect, reduces the size of the tumor. Drugs most used are progesterone alone or in association with estrogen, danazol, gestrinone and GnRH agonists.

GnRH agonists- These agents suppress gonadotropin secretion and create a hypoestrogenic state similar to that observed in the postmenopausal period. The maximum effect in reducing the tumor size is observed within 12 weeks, with no added advantage with a longer treatment. Symptoms associated with the hypoestrogenic state created include hot flashes and osteoporosis. Regrowth of leiomyomas is experienced within a few months, and for this reason its use is recommended for short-term treatment in selected cases: treatment of women approaching menopause in an effort to avoid surgery; preoperative treatment of large leiomyomas to facilitate hysteroscopic ressection or vaginal hysterectomy and as a presurgical treatment to decrease symptoms and size.

2-Surgical Treatment

a)Miomectomy- Involves the removal of single or multiple myomas while preserving the uterus.

b)Hysterectomy-It is a definitive surgical management of symptomatic uterine myomas.

References

1) Battistini, M. Myomata Yteri. Obstetrics and Gynecology - National Medical Series for Independent Study. pp 339-345. Ed. Williams and Wilkins, 1997.
2) Millard, PA. Bening diseases of the female reproductive tract: Symptons and signs. Novak's gynecology, pp 331-397, Wlliams and Wilkings, 1996.
3) Wexler, AS , Pernoll, ML. Benign disorders of the uterinecorpus - Obstetrics and Gynecology - Diagnosis and Treatment. pp 731-743. Appleton and Lange; 1994
4) Duarte G . Doenças Benignas do Corpo Uterino. Tratado de ginecologia - Halbe. pp 1073 - 1094. Ed. Roca, 1993.
5) Buttaram VS, Reiter RC. Uterine leiomyomata: Etiology, symptomatology and management. Fertil-Steril, 36:433, 1981.
6) McElin TW, Bird CC. Adenomyosis of the uterus. Obstet Gynecol Ann; 3: 425, 1974.

If you have suggestions or comments send an e-mail to Daniela Contage Siccardi

Back to Obstetrics and Gynecology

Back to Specialties

Back to Medstudents' Homepage