This chapter deals primarily with APGO Educational Topic Area:
TOPIC 53 UTERINE LEIOMYOMAS
Students should be able to outline a basic approach to patients with uterine leiomyoma, including diagnosis and the range of management options. They should identify prevalence, common presenting signs and symptoms, and physical examination findings.
Clinical Case
A 46-year-old G2P2002 comes to see you because she feels a lump in the lower part of her abdomen. She states that it does not cause her any pain, but that she has noticed an increase in the number of times she needs to urinate and estimates she urinates 10 times a day and 2 to 3 times each night. She denies any irregular bleeding and reports normal menstrual periods.
Uterine leiomyomata (also called fibroids and myomas) represent localized proliferation of smooth muscle cells surrounded by a pseudocapsule of compressed muscle fibers. The highest prevalence occurs during the fifth decade of a woman’s life, when they may be present in one in four white women and one in two African American women. Studies in which careful pathologic examination of the uterus is carried out suggest that the prevalence may be as high as 80%. Uterine fibroids vary in size, from microscopic to large multinodular tumors that literally fill the patient’s abdomen. Leiomyomata are the most common indication for hysterectomy, accounting for approximately 30% of this operation. Additionally, they account for a large number of more conservative operations, including myomectomy, uterine curettage, operative hysteroscopy, and uterine artery embolization (UAE).
Leiomyomata are classified into subgroups based on their anatomic relationship to the layers of the uterus. The three most common types are intramural (centered in the muscular wall of the uterus), subserosal (just beneath the uterine serosa), and submucosal (just beneath the endometrium). A subset of the subserosal category is the pedunculated leiomyoma, which remains connected to the uterus by a stalk. Most leiomyomata initially develop from within the myometrium as intramural leiomyomata. About 5% of uterine myomas originate from the cervix. Rarely, leiomyomata may occur without evidence of a uterine origin in places such as the broad ligament and peritoneal cavity. Leiomyomata are considered hormonally responsive, benign tumors, because estrogen may induce their rapid growth in high-estrogen states, such as pregnancy. In contrast, menopause generally causes cessation of tumor growth and even some atrophy. Estrogen may work by stimulating the production of progesterone receptors in the myometrium. In turn, progesterone binding to these sites stimulates the production of several growth factors, causing the growth of myomas. Although exact mechanisms are unknown, chromosomal translocations/deletions, peptide growth factor, and epidermal growth factor are implicated as potential pathogenic factors of leiomyomata. Sensitive DNA studies suggest that each myoma arises from a single smooth muscle cell and that, in many cases, the smooth muscle cell is vascular in origin.
The uterine smooth muscle may also develop a rare cancer, such as leiomyosarcoma. These are not thought to represent “degeneration” of a fibroid, but, rather, a new neoplasm. Uterine malignancy is more typical in postmenopausal patients who present with rapidly enlarging uterine masses, postmenopausal bleeding, unusual vaginal discharge, and pelvic pain. An enlarging uterine mass in a postmenopausal patient should be evaluated with considerably more concern for malignancy than one found in a younger woman. These heterologous, mixed tumors contain other sarcomatous tissue elements not necessarily found only in the uterus (see Chapter 49).
SYMPTOMS
Bleeding is the most common presenting symptom in uterine fibroids, and many fibroids are found incidentally. Although the kind of abnormal bleeding may vary, the most common presentation includes the development of progressively heavier menstrual flow that lasts longer than the normal duration (menorrhagia, defined as menstrual blood loss of >80 mL). This bleeding may result from significant distortion of the endometrial cavity by the underlying tumor. Three generally accepted but unproven mechanisms for increased bleeding include the following:
1. Alteration of normal myometrial contractile function in the small artery and arteriolar blood supply underlying the endometrium
2. Inability of the overlying endometrium to respond to the normal estrogen/progesterone menstrual phases, which contributes to incomplete sloughing of the endometrium
3. Pressure necrosis of the overlying endometrial bed, which exposes vascular surfaces that bleed in excess of that normally found with endometrial sloughing
Characteristically, the best example of leiomyoma contributing to this bleeding pattern is by the so-called submucous leiomyoma. In this variant, most of the distortion created by the smooth muscle tumor projects toward the endometrial cavity, rather than toward the serosal surface of the uterus. Enlarging intramural fibroids likewise may contribute to excessive bleeding if they become large enough to significantly distort the endometrial cavity.
Blood loss from this type of menstrual bleeding may be heavy enough to contribute to chronic iron-deficiency anemia and, rarely, to profound acute blood loss. The occurrence of isolated submucous (subendometrial) leiomyomata is unusual. Commonly, these are found in association with other types of leiomyomata (Fig. 48.1).
Another common symptom is a progressive increase in “pelvic pressure.” This may be a sense of progressive pelvic fullness, “something pressing down,” or the sensation of a pelvic mass. Most commonly, this is caused by slowly enlarging myomas, which, on occasion, may attain a massive size. These leiomyomata are the most easily palpated on bimanual or abdominal examination and contribute to a characteristic “lumpy-bumpy,” or cobblestone, sensation when multiple myomas are present. Occasionally, these large myomas present as a large asymptomatic pelvic or even abdominopelvic mass. Such large leiomyomata may cause an uncommon but significant clinical problem: pressure on the ureters as they traverse the pelvic brim leading to hydroureter (dilation of the ureter) and possibly hydronephrosis (dilation of the renal pelvis and calyces). These conditions can also occur if fibroids lower within the pelvis grow laterally between the leaves of the broad ligament. Occasionally, large fibroids can cause urinary symptoms or problems with defecation.
Another presentation is the onset of secondary dysmenorrhea. Other pain symptoms, although rare, may be the result of rapid enlargement of a leiomyoma. This can result in areas of tissue necrosis or areas of subnecrotic vascular ischemia, which contribute to alteration in myometrial response to prostaglandins similar to the mechanism described for primary dysmenorrhea. Occasionally, torsion of a pedunculated myoma can occur, resulting in acute pain. Dull, intermittent, low midline cramping (labor-like) pain is the clinical presentation when a submucous (subendometrial) myoma becomes pedunculated and progressively prolapses through the internal os of the cervix.
FIGURE 48.1. Common types of leiomyomata.
DIAGNOSIS
The diagnosis of fibroids is usually based on physical examination or imaging studies. Occasionally, irregularities of the uterine cavity are detected during endometrial sampling. Often the diagnosis is incidental to pathologic assessment of a uterine specimen removed for other indications. On abdominopelvic examination, uterine leiomyomata usually present as a large, midline, irregular-contoured mobile pelvic mass with a characteristic “hard feel” or solid quality. The degree of enlargement is usually stated in terms (“weeks size”) that are used to estimate equivalent gestational size.
The fibroid uterus is described separately from any adnexal disease, although, on occasion, a pedunculated myoma may be difficult to distinguish from a solid adnexal mass.
Pelvic ultrasound may be used for confirmation (when necessary) of uterine myomas, but the diagnosis remains a clinical one. There may be areas of acoustic “shadowing” amid otherwise normal myometrial patterns, and there may be a distorted endometrial stripe. Often, a round mass is identified within the myometrium. Occasionally, cystic components may be seen as hypoechogenic areas and are consistent in appearance with myomas undergoing degeneration. Adnexal structures, including the ovaries, are usually identifiable separately from these masses.
Computerized axial tomography and magnetic resonance imaging (MRI) may be useful in evaluating extremely large myomas when ultrasonography may not characterize a large myoma well. Hysteroscopy, hysterosalpingography, and saline infusion ultrasonography are the best techniques for identifying intrauterine lesions such as submucosal myomata and polyps. An indirect appreciation for uterine enlargement may be gained by uterine sounding, which may be done as part of an endometrial biopsy. If a patient has irregular uterine bleeding and endometrial carcinoma is a consideration, endometrial sampling is useful to evaluate for this possibility, independent of the presence of myomas.
Hysteroscopy may be used to evaluate the enlarged uterus by directly visualizing the endometrial cavity. The increased size of the cavity can be documented, and submucous fibroids can be visualized and removed. Although the efficacy of hysteroscopic removal (resection) of submucous myomas has been documented, long-term follow-up suggests that up to 20% of patients require additional treatment during the subsequent 10 years.
Surgical evaluation may be required when physical examination and ultrasound cannot differentiate whether the patient has a leiomyomata or other potentially more serious disease such as adnexal neoplasia. Laparoscopic resection of subserosal or intramural myoma has gained in popularity, although the long-term benefit of this procedure has not been well established.
TREATMENT
Most patients with uterine myomas do not require (surgical or medical) treatment. Treatment is generally first directed toward the symptoms caused by the myomas. If this approach fails (or there are other indications present), surgical or other extirpative procedures may be considered.
For example, if a patient presents with menstrual aberrations that are attributable to the myomas, with bleeding that is not heavy enough to cause her significant hygiene or lifestyle problems—and the bleeding is also not contributing to iron-deficiency anemia—reassurance and observation may be all that are necessary. Further uterine growth may be assessed by repeat pelvic examinations or serial pelvic ultrasonography.
Medical Treatment
An attempt may be made to minimize uterine bleeding by using intermittent progestin supplementation and/or prostaglandin synthetase inhibitors, which decrease the amount of secondary dysmenorrhea and amount of menstrual flow. Iron and vitamin supplementation should be considered if the patient is anemic. If significant endometrial cavity distortion is caused by intramural or submucous myomas, hormonal supplementation may be ineffective. If effective, this conservative approach can potentially be used until the time of menopause. Progestin can be delivered in the form of oral contraceptives, the levonorgestrel intrauterine system, progestin injections, or pills. Nonsteroidal anti-inflammatory drugs and, more recently, antifibrinolytic agents, such as tranexamic acid, have been used to treat menorrhagia with mixed results in patients with fibroids.
Pharmacologic inhibition of estrogen secretion has been used to treat fibroids. This is particularly applicable in the perimenopausal years when women are more likely anovulatory, with relatively more endogenous estrogen. Pharmacologic removal of the ovarian estrogen source can be achieved by suppression of the hypothalamic–pituitary–ovarian axis through the use of gonadotropin-releasing hormone agonists (GnRH analogs), which can reduce fibroid size by as much as 40% to 60%. This treatment is commonly used before a planned hysterectomy to reduce blood loss as well as the difficulty of the procedure. It can also be used as a temporizing medical therapy until natural menopause occurs. Therapy is generally limited to 6 months of drug treatment secondary to the risk of clinically significant bone loss during this hypoestrogenic state. Therapy can be extended beyond 6 months if hormonal add-back therapy is used concurrently to decrease the rate of bone loss. More recently, aromatase inhibitors have been used, but this treatment is not well studied.
In patients with an adequate endogenous estrogen source, this treatment does not permanently reduce the size of uterine myomas, because withdrawal of the medication predictably results in regrowth of the myomas. Although less successful, other pharmacologic agents such as danazol have also been used as medical treatment for myomas by reducing endogenous production of ovarian estrogen. It is important to address the multiple side effects associated with danazol with patients prior to use.
Surgical Treatment
Of the surgical options available, myomectomy is warranted in patients who desire to retain childbearing potential or whose fertility is compromised by the myomas, creating significant intracavitary distortion. Indications for a myomectomy include a rapidly enlarging pelvic mass, symptoms unrelieved with medical management, and enlargement of an asymptomatic myoma to the point of causing hydronephrosis. Contraindications to myomectomy include current pregnancy, advanced adnexal disease, malignancy, and the situation in which enucleation of the myomas would completely compromise the function of the uterus. Potential complications of myomectomy include excessive intraoperative blood loss; postoperative hemorrhage, infection, and pelvic adhesions; and even the need for emergency hysterectomy. Within 20 years of a myomectomy procedure, one in four women has a hysterectomy, the majority for recurrent symptomatic leiomyomas.
Although hysterectomy is commonly performed for uterine myomas, it should be considered as definitive treatment only in symptomatic women who have completed childbearing. Indications should be specific and well documented. Depending on the size of the fibroids and the skill of the surgeon, both myomectomy and hysterectomy can be performed using minimally invasive techniques. The ultimate decision whether to perform a hysterectomy should include an assessment of the patient’s future reproductive plans as well as careful assessment of clinical factors, including the amount and timing of bleeding, the degree of enlargement of the tumors, and the associated disability for the individual patient. Asymptomatic uterine myomas alone do not necessarily warrant hysterectomy.
Other Therapies
Other therapeutic modalities have been introduced, including myolysis (via direct procedures or by the delivery of external radio or ultrasonic energy) and UAE. The safety and efficacy of UAE have been studied to the point that it is now considered a viable alternative to hysterectomy and myomectomy for selected patients. The procedure involves selective uterine artery catheterization with embolization using polyvinyl alcohol particles, which creates acute infarction of the target myomas. For maximal efficacy, bilateral uterine artery cannulation and embolization are necessary. In assessing outcomes data, the three most common symptoms of myomas—bleeding, pressure, and pain—are ameliorated in over 85% of patients. Acute postembolization pain that requires hospitalization occurs in approximately 10% to 15% of patients. Other complications include delayed infection and/or passage of necrotic fibroids through the cervix up to 30 days after the procedure. Occasionally, these complications necessitate hysterectomy. Although successful pregnancies have been reported after selective embolization, UAE is currently not recommended as a procedure to consider in patients who desire future childbearing.
MRI-guided focused ultrasound surgery is a new approach used to treat myomata. A focused ultrasound unit delivers sufficient ultrasound energy to a targeted point to raise the temperature to approximately 70°C. This results in coagulative necrosis and a decrease in myoma size. Treatment is associated with minimal pain and appears to improve selfreported bleeding patterns and quality of life.
EFFECT OF LEIOMYOMATA IN PREGNANCY
Although leiomyomata may be associated with infertility, patients with leiomyoma do become pregnant. Pregnancy with small leiomyomata is usually unremarkable, with a normal antepartum course, labor, and delivery. However, women with multiple myomas or large myomas may have significantly increased rates of preterm labor, fetal growth abnormalities, malpresentation, pelvic pain, abnormal labor, cesarean delivery, and postpartum hemorrhage. Myomas may sometimes cause pain, because they can outgrow their blood supply during pregnancy, resulting in red, or carneous, degeneration.
Bed rest and strong analgesics are usually sufficient as treatment, although, on occasion, myomectomy may be needed. The risk of abortion or preterm labor following myomectomy during pregnancy is relatively high, so that prophylactic β-adrenergic tocolytics are frequently used. Myomectomy during pregnancy should be limited to myomas with a discrete pedicle that can be clamped and easily ligated. Myomas should otherwise not be removed during the time of delivery, because bleeding may be profuse, resulting in hysterectomy. Vaginal birth after myomectomy is controversial and must be decided on a case-by-case basis. Generally, if removal of the myoma requires entry into the endometrial cavity, cesarean delivery is recommended because there is a significant risk of uterine rupture during a subsequent pregnancy, even at times remote from labor. Rarely, myomas are located below the fetus, in the lower uterine segment or cervix, causing a soft tissue dystocia, leading to a need for cesarean birth.
Clinical Follow-Up
You do a physical examination and note the lump she describes. You order an ultrasound, and it demonstrates a single 7-cm fibroid over the lower anterior portion of her uterus. You counsel her about the options, and, together, you formulate a plan for myomectomy, which she undergoes without complication. Two months after surgery, her urinary patterns are back to normal.
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