Leiomyomas

ALSO KNOWN AS: Myomas, fibroids, uterine fibroids, genital leiomyomas, angioleiomyomas, piloleiomyomas

RELATED CONDITIONS: Leiomyosarcomas

DEFINITION: Leiomyomas are benign tumors that arise from the smooth muscle of the digestive tract, the arrector pili muscle in hair follicles (piloleiomyoma), the vascular smooth muscle in blood vessels (angioleiomyoma), or the dartos muscles of the nipples or genital tract (genital leiomyoma). Piloleiomyomas, angioleiomyomas, and genital leiomyomas are all classified as cutaneous leiomyomas. While any organ possessing smooth muscle may become involved, the myometrium (the muscular layer of the uterus) is the most common site. Leiomyomas may arise at any location in the myometrium as a single mass, cluster, or diffuse disease.

Risk factors: One is a family history of leiomyomas, especially a condition known as hereditary leiomyomatosis and renal cell cancer (HLRCC) or Reed syndrome, which presents with tumors involving the skin and uterus and is inherited in an autosomal dominant fashion but expressed variably. The responsible gene, FH, is located on the long arm of chromosome 1 (1q42.1). Women are at risk of developing uterine leiomyomas during their reproductive years. Other risk factors include beginning oral contraceptives before age sixteen, an increased body mass index, and early menarche.

Etiology and the disease process: The origin of cutaneous leiomyomas is still uncertain. The most common symptom is pain, the mechanism of which remains poorly understood. It has been postulated that the pain is caused by the tumors either exerting pressure on nerve fibers or stimulating the sympathetic nervous system so that the muscles contract. Uterine leiomyomas have been linked with various mutations of the FH gene. They occur only in the presence of estrogen and progesterone stimulation and arise due to the overproliferation of smooth muscle and connective tissue cells within the myometrium. Estrogen- and progesterone-receptor stimulation on these cells accelerates or decreases proliferation, suggesting that leiomyomas depend on estrogen and progesterone.

Incidence: Leiomyomas outside the uterus are rare, but between 40 to 80 percent of women will develop a uterine leiomyoma by age forty-five. Around 80 percent of Black women and 70 percent of White women develop leiomyomas by age fifty. Less than 1 percent of uterine leiomyoma cases will experience malignant transformation (leiomyosarcoma). Leiomyomas account for around 0.5 percent of all esophageal tumors.

Symptoms: Most patients with multiple piloleiomyomas experience pain, either spontaneous or induced by cold or pressure. Pain is also the most common symptom of angioleiomyomas, though around 40 percent of cases are asymptomatic. Pregnancy or menstruation may trigger symptoms. Esophageal tumors are generally asymptomatic until they reach five centimeters or more in diameter. At this point, they may cause dysphagia (difficulty swallowing), chest pain or discomfort, esophageal obstruction, vomiting, and, on rare occasions, gastrointestinal bleeding. A woman of reproductive age with a leiomyoma proximal to the vascular endometrium will experience bleeding and may exhibit fatigue and pallor. A uterine leiomyoma may be felt through the abdominal wall and mistaken for pregnancy. However, a pregnancy test would be negative. Subtler symptoms may include menometrorrhagia (increased, frequent, and irregular bleeding from the vagina), infertility, or compression of the bladder and ureter (urine duct from the kidney to the bladder). A blood test may reveal significant anemia when the woman is experiencing frequent and substantial blood loss.

Screening and diagnosis: A diagnosis of an extrauterine leiomyoma may be confirmed by an excisional biopsy, where excision of the entire mass is also therapeutic. A barium-contrast study may show a “punched-out” defect in the esophagus. Ultrasound and (MRI) are not as helpful. A pelvic ultrasound may reveal a vague mass darker than the surrounding normal tissue within the myometrium. A distortion in the uterine contour may be the only hint of a leiomyoma. An endometrial biopsy is also performed to rule out endometrial cancer. Specific screening tests other than regular pelvic examinations are not available for leiomyomas.

Treatment and therapy: Apart from excisional biopsy, pain from extrauterine leiomyomas may be alleviated with calcium-channel blockers (nifedipine), alpha-receptor blockers (phenoxybenzamine), or gamma-aminobutyric acid (GABA) analogs (gabapentin). Enucleation with repair may be sufficient in esophageal masses.

Treatment of uterine leiomyomas may be conservative or curative. If the patient is symptomatic (for example, anemic from chronic bleeding), no longer desires to bear children, wishes to be pain-free, and is amenable to a hysterectomy (surgical removal of the uterus), a curative approach is adopted. A conservative approach is preferable if the patient is relatively young and desires to bear children.

Conservative treatment options range from watchful waiting and myomectomy to newer procedures such as uterine arterial embolization (UAE). UAE involves injecting polyvinyl alcohol foam particles into the uterine arteries, which occludes the leiomyoma’s blood supply, inducing tumor involution. As only 10 to 20 percent of patients require definitive treatment, with most leiomyomas shrinking after menopause and pregnancy, monitoring with serial pelvic ultrasound may be done. A myomectomy, in which the leiomyomas are surgically removed, seeks to preserve as much of the muscular integrity of the uterus as possible. Excessive blood loss during an operation may be prevented by chemotherapy with a gonadotropin-releasing hormone (GnRH) analog such as nafarelin or leuprolide acetate. A fertility workup, including fallopian tube patency with a hysterosalpingogram and semen analysis, should also be performed. Curative options include an abdominal or vaginal hysterectomy to remove the uterus along with the mass.

Prognosis, prevention, and outcomes: The overall prognosis of uncomplicated leiomyomas is excellent. Most leiomyomas are benign, so patients undergoing surgical excision or a hysterectomy rarely experience recurrence. Postmenopausal women with a history of leiomyoma on hormone replacement may have a recurrence. No preventive measures against developing a leiomyoma are known. 

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