What is a leiomyoma (uterine fibroid) of the uterus?

What is a Uterine Leiomyoma (Fibroid)?

Uterine leiomyomas, commonly called fibroids, are benign smooth muscle tumors originating from the myometrium that represent the most common pelvic tumors in women and the most common soft-tissue tumors in the entire body. 1

Fundamental Characteristics

Pathologic Nature:

• Leiomyomas are well-vascularized, benign, monoclonal tumors characterized by increased smooth-muscle cell proliferation and collagen deposition 1
• They represent sex steroid-responsive clonal expansions of individual myometrial cells 1
• The histology is virtually indistinguishable from normal myometrium, with highly variable cellularity 1
• These tumors grow in a spherical nodular fashion with distinct demarcation from surrounding normal myometrium, reflecting their clonal origin 1

Epidemiology and Prevalence

Incidence:

• Affect 20-25% of women during their reproductive years clinically 1
• Estimates suggest up to 70-80% of women have identifiable leiomyomata present in their uterus at menopause 1
• More common in African-American women with a non-Mendelian inheritance pattern 1
• Occur predominantly during reproductive years (ages 15-49) 2

Clinical Impact:

• Approximately 200,000 hysterectomies and 20,000 myomectomies are performed annually in the United States because of symptomatic leiomyomata 1
• The incidence far exceeds the frequency of clinical problems, as many remain asymptomatic 1

Clinical Presentation

Symptom Spectrum:

• Many women remain completely asymptomatic despite tumor presence 1
• When symptomatic, can cause menometrorrhagia, dysmenorrhea, pelvic pain, and pelvic pressure 1
• May cause reproductive failure, infertility, and recurrent pregnancy loss 1, 2
• Can produce compression symptoms of adjacent pelvic viscera 1
• Tumors can attain very large size with few symptoms, or small leiomyomata may cause massive uterine bleeding and pain 1

Pathophysiology and Growth Factors

Hormonal Influence:

• Growth is clearly related to gonadal steroids, as they are not noted prior to puberty and typically regress after menopause 1
• Possess sex-steroid receptors (estrogen and progesterone) 1
• Often dramatically enlarge during pregnancy 1
• Can be made to shrink with medically induced hypogonadism 1

Molecular Mechanisms:

• Approximately one-third have clonal chromosomal aberrations, though these are not consistent between individual leiomyomata even in the same woman 1, 3
• Heterogeneous cytogenetic abnormalities include chromosomal 12:14 translocation resulting in abnormal expression of the high mobility group IC gene 1
• Loss of tuberous sclerosis 2 gene has been shown to result in leiomyoma development 1
• Growth factor dysregulation plays a key role, including platelet-derived growth factor, heparin-binding epidermal growth factor, hepatoma-derived growth factor, and basic fibroblast growth factor 1
• TGF-β3 expression is 5-fold higher in leiomyomas compared to normal myometrium 1

Anatomic Features and Degeneration

Structural Characteristics:

• Areas of fibrosis and calcification are often interspersed, especially after degeneration and in postmenopausal women 1
• When rapid growth occurs (occasionally in pregnancy), the central area may undergo necrosis and be replaced by hyalinized degeneration 1
• Many leiomyomata have limited growth potential and remain static in size until sex steroid levels decline at menopause 1

Malignant Potential

Critical Distinction:

• For practical purposes, these tumors should be considered benign in premenopausal women 1
• Leiomyosarcomas comprise only 0.1% of all uterine tumors 1, 3
• Risk increases with age: 1.7% of women undergoing hysterectomy for leiomyomata in their seventh decade have leiomyosarcoma 1, 3
• Molecular evidence does not suggest progression from benign leiomyomata to leiomyosarcoma 1, 3
• Histologic criteria for malignancy include increased mitoses, cellular pleomorphism, and thrombotic degeneration 1, 4

Current Treatment Landscape

Surgical Options:

• Current therapies are limited primarily to surgery 1
• Hysterectomy is most often used for definitive treatment 1
• Myomectomy when preservation of childbearing is desired, though recurrence occurs in approximately one-third of patients 1
• Intracavitary and submucous leiomyomata can be removed by hysteroscopic resection 1

Medical Management:

• GnRH agonist-induced hypogonadism can reduce volume, but severe side effects and prompt recurrences limit use to short-term goals such as reversing anemia or shrinking tumors prior to hysteroscopic resection 1
• Future nonsurgical treatments may include compounds that block specific growth factors regulating proliferation and collagen production 1