Description

• Uterine leiomyomas are well-circumscribed, pseudoencapsulated, benign monoclonal tumors composed mainly of smooth muscle with varying amounts of fibrous connective tissue (1,2).
• 3 major subtypes:
  • Subserous: Common; external; may become pedunculated
  • Intramural: Common; within myometrium; may cause marked uterine enlargement
  • Submucous: ~5% of all cases; internal, evoking abnormal uterine bleeding and infection; occasionally protruding from cervix
• Rare locations: Broad, round, and uterosacral ligaments
• System affected: Reproductive
• Synonym(s): Fibroids; myoma; fibromyoma; myofibroma; fibroleiomyoma

Epidemiology

• Cumulative incidence is 70%, highest in perimenopausal age group
• Incidence increases with each decade during reproductive years
• Not seen in premenarchal females
• Predominant sex: Females only
• 3× more frequent; occurs earlier in African Americans

• 4–11% of all women
• 20–40% of women in reproductive years (2)

Risk Factors

• African American heritage
• Early menarche (<10 years)
• Nulliparous
• Hypertension
• Familial predisposition
• Obesity
• Alcohol

• ∼50% of leiomyomas have an abnormal karyotype.
• Most common cytogenetic abnormalities are deletions on chromosome 7.

Pathophysiology

Enlargement of benign smooth muscle tumors that may lead to symptoms affecting the reproductive, GI, or genitourinary system

Etiology

Complex multifactorial process involving transition from normal myocyte to abnormal cells and then to visibly evident tumor (monoclonal expansion):

• Hormones (1): Increases in estrogen and progesterone are correlated with myoma formation (i.e., rarely seen before menarche). Estrogen receptors in myomas bind more estradiol than normal myometrium (2).
• Growth factors (1):
  • Increased smooth muscle proliferation (transforming growth factor β [TGF-β], basic fibroblast growth factor [bFGF])
  • Increase DNA synthesis (epidermal growth factor [EGF], platelet-derived growth factor [PDGF], activin, myostatin)
  • Stimulate synthesis of extracellular matrix (TGF-β)
  • Promote mitogenesis (TGF-β, EGF, insulin-like growth factor [IGF], prolactin)
  • Promote angiogenesis (bFGF, vascular endothelial growth factor [VEGF])
• Vasoconstrictive hypoxia (1): Proposed, but not confirmed, mechanism of myometrial injury during menstruation

Commonly Associated Conditions

Endometrial and breast cancer also associated with high unopposed estrogen stimulation.