Uterine fibroids

Uterine fibroids, also called myomas or leiomyomas, are benign fibromuscular tumours of the myometrium (1).

Uterine leiomyomas occur in about one half of all women older than age 35 years and in up to 80 percent of women by age 50 (2,3). They are by far the most common gynecological and pelvic neoplasm, more common in black than white women, associated with obesity, with an apparent increased familial incidence (4-6).

Each leiomyoma arises from a single neoplastic cell within the smooth muscle of the myometrium (7).

The cause of uterine leiomyomas is unknown. Hormonal responsiveness to estrogen and progesterone is demonstrated in vitro and in vivo, with the potential to grow during pregnancy, as well as to decrease in size and degenerate after menopause (8).

Grossly, a leiomyoma is a nodular tumour that varies in size and number and may be microscopic or huge in size. Its consistency varies from hard and stony (as with a calcified leiomyoma) to soft (as with cystic degeneration), with a usual consistency described as firm or rubbery. The margins are blunt, noninfiltrating, and are usually separated from the myometrium by a pseudocapsule of connective tissue, which allows easy enucleation at the time of surgery. Degenerative changes are reported in approximately two thirds of all surgical specimens (9). “Malignant degeneration” of a pre-existing leiomyoma is extremely uncommon (10). Leiomyosarcoma is a rare malignant neoplasm composed of cells that have smooth muscle differentiation, arising de novo via distinct pathogenetic pathways. Cytogenetic studies distinguished leiomyomas from smooth muscle tumours of uncertain malignant potential (STUMP) (defined as having 5-9 mitoses per 10 high-power fields [hpf] with giant cells, or with a lower mitotic count [2–4 mitoses/10 hpf] with atypical nuclear features or giant cells) and leiomyosarcoma (defined as having 10 mitoses/10 hpf or greater) (11).

Uterine leiomyomas are frequently diagnosed on the basis of clinical findings of an enlarged, irregular uterus on pelvic examination. However, most leiomyomas, depending on size, number, and location, are asymptomatic, likely noted on ultrasonography as an incidental finding. The most common initial symptom associated with fibroids, and the one that most frequently leads to surgical intervention, is menorrhagia. Pelvic pain and infertility or recurrent pregnancy loss may also be present, as well as urinary or intestinal bulk symptoms due to bladder or rectosigmoid compression, respectively.

Ultrasonography (US) is the first-line imaging tool for any suspected structural anomaly of the female pelvis as well as the most appropriate imaging modality for abnormal uterine bleeding (12). It has high sensitivity and specificity in diagnosing leiomyomas, but this can vary with the operator’s experience, ranging from 65 to 99%. Pelvic US usually consists of a combined approach to include both transabdominal (TAS) and transvaginal (TVS) imaging. The latter is generally considered to be more sensitive and specific, with greater contrast and spatial resolution, in particular in obese patients. The former, on the other hand, is helpful in women with a large uterus extending  out of  the pelvis, thus providing an anatomic overview to better estimate overall uterine size (13). 

A uterine leiomyoma is seen typically on US as a well-defined round or oval lesion within or attached to the myometrium, with smooth contour and varying echogenicity.  Often the mass exhibits shadows at the edge of the lesion and/or internal fan-shaped shadowing, and circumferential flow around the lesion on colour- or power-Doppler imaging.  A 3D reconstruction of the uterus can be performed at the same time to map the location of the fibroids.

For incomplete visualization or indeterminate US findings, MRI is recommended. It is useful especially in cases of multiple leiomyomas (> 4) or a large volume uterus (> 375 mL) (18).

Localization of fibroids

Hysteroscopy has been traditionally considered as the gold standard technique in the diagnosis of submucous leiomyomas. Transvaginal sonohysterography (SCSH) can be used in adjunct with TVS to improve the sensitivity in diagnosing and correctly classifying these lesions, either at 2D- or at 3D-SCSH (16,17).

Differential diagnosis

Adenomyosis is diagnosed in presence of asymmetrical thickening, myometrial cysts and/or hyperechoic islands, fan-shaped shadowing, echogenic subendometrial lines and buds, irregular junctional zone, and translesional vascularity (14). Uterine sarcoma should be suspected in presence of a solid mass with inhomogeneous echogenicity, sometimes with irregular cystic areas, moderately or very well vascularized (15).

The risk of recurrence for leiomyomas has been reported to be as high as 50% after myomectomy, with up to one third requiring repeat surgery (19, 20). Pregnancies  concurrent with  fibroids  or after treatment can be complicated by miscarriage, preterm labor, intrauterine growth restriction, malpresentation and/or abnormal placentation depending on myoma on size, number, and location (21, 22). Removal of submucosal fibroids seems to improve fertility outcomes; subserosal fibroids do not affect fertility outcomes; intramural fibroids appear to decrease fertility, but the results of myomectomy are unclear (23).

The management of uterine leiomyomas depends on symptoms, patient's age and preference, and the experience and skills of the clinician. It may include observation or medical, surgical and radiologic-based therapies (1).

Judicious patient observation and sonographic follow-up are primarily indicated for asymptomatic uterine leiomyomas, with periodic examinations (3 to 6 months, then yearly) indicated to rule out rapid growth. Medical treatment, based on oral contraceptives, selective estrogen or progesterone receptor modulators and GnRH antagonists, should be considered in selected symptomatic patients. These patients include women approaching menopause (to avoid surgery), women with medical contraindications to surgery, and pre-operative treatment before myomectomy or hysterectomy to reduce myoma volume and/or to allow recovery of normal hemoglobin levels (2, 24).  Surgical intervention is reserved for specific indications and associated symptoms (25), such as abnormal uterine bleeding, infertility or recurrent pregnancy loss with distortion of the endometrial cavity, urinary symptoms with compression or discomfort symptoms for markedly enlarged uterine size and/or rapid lesion growth to exclude uterine sarcoma (6, 26).

Hysterectomy has long been considered as the definitive management of symptomatic uterine leiomyomas. However, nowadays myomectomy is a robust alternative to hysterectomy for young patients who desire childbearing or prefer to retain the uterus.

Laparoscopic myomectomy minimizes the size of the abdominal incision, although skilled surgical techniques are required for the risks to convert to a laparotomy and the risk of uterine rupture in a subsequent pregnancy (25). Hysteroscopic resection is the standard technique to manage submucous myomas (type 0, 1 and 2) (27).

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12. Munro, M.G., et al., FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet, 2011. 113(1): p. 3–13.

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20. Fedele L, Parazzini F, Luchini L, et al. Recurrence of fibroids after myomectomy: a transvaginal ultrasonographic study. Hum Reprod 1995;10:1795–1796.

21. Practice Committee of the American Society for Reproductive Medicine. Myomas

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25. American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Gynecology. Surgical alternatives to hysterectomy in the management of leiomyomas. Practice Bulletin 16. Washington, DC: American College of Obstetricians and Gynecologists, 2000.

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27. Leone FPG, Calabrese S, Marciante C, Cetin I, Ferrazzi E. Feasibility and long-term efficacy of hysteroscopic myomectomy for myomas with intramural development by the use of non-electrical "cold" loops. Gynecological Surgery 2012 May; 9 (2): 155-161.

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