Leiomyomas result from monoclonal proliferation of uterine smooth muscle cells or less commonly from smooth muscle cells of uterine blood vessels. They can range in size from millimeters to large tumors reaching the costal margin. These tumors may be solitary or multiple and are classified by location within the uterus. These cells express estrogen synthetase and aromatase and are capable of converting androgens into estrogen.

Submucosal fibroids develop from myometrium just deep to the endometrial lining. These can often protrude into the endometrial cavity or, if pedunculated, can even grow past the internal cervical os. The main symptoms of this subgroup of fibroids include heavy or abnormal bleeding, reduced fertility, miscarriages, and preterm labor.

Intramural fibroids, located within the uterine corpus wall, may distort the uterine cavity. Cervical fibroids are intramural but found in the uterine cervix.

Subserosal fibroids develop below the serosal layer, are often pedunculated, and occasionally extend between folds of the broad ligament. They do not cause abnormal uterine bleeding but more likely contribute to bulk symptoms.

Extrauterine fibroids are leiomyomas that are found outside of the uterus. They are usually the result of hematogenous spread of neoplastic smooth muscle cells from the uterus. Extrauterine fibroids are histologically and clinically identical to the intrauterine fibroids described earlier. Extrauterine locations most commonly include the genitourinary tract, the gut mesentery, and the cardiopulmonary system. Other rarer locations include the spinal cord and blood vessels.

A genetic basis for the presence and growth of uterine leiomyomas appears likely. Family history of leiomyomas increases an individual’s risk 1.5- to 3.5-fold. It has been suggested that up to 40% of leiomyomas have associated chromosome abnormalities, including deletion of portions of 7q, trisomy 12, or rearrangements
(translocations) of chromosomes 6, 10, and 12. The Val158Met polymorphism on the catechol-O-methyltransferase (COMT) gene has been found to be a protective factor against uterine leiomyoma. The incidence of leiomyomas is estimated to be threefold greater among African American women and often occur at a younger age in this population. In addition, fibroids in African American women respond differently than those in white women. Decreased vitamin D levels may be an etiology for this increased incidence, as darker skin inhibits autologous vitamin D production.

The growth of uterine leiomyomas is related to circulating estrogen exposure. Progesterone may exert an antiestrogen effect on the growth of leiomyomas. Fibroids are most prominent and demonstrate maximal growth during the reproductive years and tend to regress after menopause. Whenever leiomyomas grow after menopause, malignancy (e.g., leiomyosarcoma) must be considered in the differential diagnosis. Leiomyomas commonly grow during pregnancy, most likely due to the enhanced uterine blood supply that accompanies pregnancy and edematous changes in these tumors.

As leiomyomas grow, they risk diminution of blood supply, which leads to a continuum of degenerative changes, including calcium deposition. Calcific change can be appreciated radiographically as a diffuse honeycomb pattern, a series of concentric rings, or a solid calcific mass. Necrosis, cystic changes, and fatty degeneration are manifestations of compromised blood supply secondary to growth or infarction from torsion of a pedunculated leiomyoma. Histologically, degenerative changes in myomas may also be seen with progesterone stimulation or, less frequently, malignant transformation.

Although malignant degeneration of leiomyomas is possible, most leiomyosarcomas are thought to arise de novo. Leiomyosarcomas are diagnosed on the basis of counts of 10 or more mitotic figures per 10 high-power fields (HPFs). Those tumors with 5 to 10 mitotic figures per 10 HPFs are referred to as smooth muscle tumors of uncertain malignant potential. Tumors with <5 mitotic figures per 10 HPFs and little cytologic atypia are classified as cellular leiomyomas.