Uterine fibroids

Uterine fibroids (singular Uterine Fibroma) (leiomyomata, singular leiomyoma) are benign tumors which grow from the muscle layers of the uterus. They are the most common neoplasm in females, and may affect about 25% of white and 50% of black women during the reproductive years. Uterine fibroids often do not require treatment, but when they are problematic, they may be treated surgically or with medication — possible interventions include a hysterectomy, hormonal therapy, a myomectomy, or uterine artery embolization. Uterine fibroids shrink dramatically in size after a woman passes through menopause.

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Pathology and histology

Leiomyomas grossly appear as round, well circumscribed (but not encapsulated), solid nodules that are white, or tan whorled. The size varies, from microscopic to lesions of considerable size. Typically lesions the size of a grapefruit or bigger are felt by the patient herself through the abdominal wall. Microscopically, tumor cells resemble normal cells (elongated, spindle-shaped, with a cigar-shaped nucleus) and form bundles with different directions (whirled). These cells are uniform in size and shape, with scarce mitoses. There are three benign variants: bizarre (atypical); cellular; and mitotically active.

Leiomyomas arise from the smooth muscle (myometrium) and of the components of the Extracellular Matrix (ECM). [1]

Leiomyomas are estrogen sensitive and have estrogen receptors. They may enlarge rapidly during pregnancy due to increased estrogen levels. As estrogen levels decline with menopause, fibroids tend to regress after menopause. Hormonal therapy is based on these facts.

More recent studies have revealed a possible role of progesterone and progestins to fibroid growth as well,^[1][2] and applicability of progestin agonists as part of treatment are currently being considered.^[3]

Symptoms

The symptoms depend on the size, location, number, and the pathological findings. Fibroids, particularly when small, may be entirely asymptomatic. Generally, symptoms relate to the location of the lesion and its size. Important symptoms include abnormal gynecologic hemorrhage, pain, urinary frequency or retention, and in some cases, infertility. During pregnancy they may be the cause of miscarriage, bleeding, premature labor, or interference with the position of the fetus.

Location

Fibroids may be single or multiple. Most fibroids start in an intramural location,- that is the layer of the muscle of the uterus. With further growth, some lesions may develop towards the outside of the uterus (subserosal or pedunculated), some towards the cavity (submucosal or intracavitary). Lesions affecting the cavity tend to bleed more and interfere with pregnancy. Secondary changes that may develop within fibroids are hemorrhage, necrosis, calcification, and cystic changes. Less frequently, leiomyomas may occur at the lower uterine segment, cervix, or uterine ligaments.

Diagnosis

Diagnosis is usually accomplished by bimanual examination, better yet by gynecologic ultrasonography, commonly known as "ultrasound." Sonography will depict the fibroids as focal masses with a heterogeneous texture, which usually cause shadowing of the ultrasound beam. In cases where a more precise assay of the fibroid burden of the uterus is needed, also magnetic resonance imaging (MRI) can be used to definite the depiction of the size and location of the fibroids within the uterus. While no imaging modality can clearly distinguish between the benign uterine leiomyoma and the malignant uterine leiomyosarcoma, because of the rarity of the latter and the prevalence of the former until that time, for practical purposes, there is no result unless it is evidence of local invasion is present, though more recent studies have improved diagnostic capabilities using MRI.^[4] For this reason, biopsy is rarely performed and if performed, is rarely diagnostic.

Treatment

The presence of a fibroid does not mean that it needs to be treated; it is expectantly depending on the symptomatology and presence of related conditions, such as anemia. The presence of uterine fibroids can cause problems which can be solved by:

• Operation: Hysterectomy or myomectomy can be performed. Based on the size and location of the lesion, different approaches can be considered: laparotomy, laparoscopy, or hysteroscopy.
• Uterine artery embolization (UAE): Using interventional radiology techniques, the Interventional physician occludes both uterine arteries, thus reducing blood supply to the fibroid(s).

• Medical therapy: First line treatment may involve oral contraceptive pills, either combination pills or progestin-only, in an effort to manage symptoms. If unsuccessful, further medical therapy involves the use of medication to reduce estrogens in an attempt to create a medical menopause-like situation. Gonadotropin-releasing hormone analogs are used for this. GNRH analogs, however, are short term treatments only. Selective progesterone receptor modulators, such as Progenta, were under investigation in 2005, because their use as therapeutic agents was desired.
• HIFU (High intensity focused ultrasound), also called Magnetic Resonance guided Focused Ultrasound, is a non-invasive intervention (requiring no incision) that uses high intensity focused ultrasound waves to ablate (destroy) tissue in combination with Magnetic Resonance Imaging (MRI), which guides and monitors the treatment. This technique is relatively new; it was approved by the FDA in 2005.

Malignancy

Very few lesions are or become malignant. Signs that a fibroid may be malignant are rapid growth or growth after menopause. Such lesions are typically a leiomyosarcoma on histology. There is no consensus among pathologists regarding the transformation of Leiomyoma into a sarcoma. Most pathologists believe that a Leiomyosarcoma is a de novo disease.

See also

• Fibroma

References

1. ^ Nisolle M, Gillerot S, Casanas-Roux F, Squifflet J, Berliere M, Donnez J (1999). "Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone receptors A and B in leiomyomata and normal myometrium during the menstrual cycle and under gonadotrophin-releasing hormone agonist therapy". Hum. Reprod. 14 (11): 2844-50. PMID 10548634.
2. ^ Advances in Uterine Leiomyoma Research: The Progesterone Hypothesis. Retrieved on 2007-08-25.
3. ^ Celik H, Sapmaz E (2003). "Use of a single preoperative dose of misoprostol is efficacious for patients who undergo abdominal myomectomy". Fertil. Steril. 79 (5): 1207-10. PMID 12738519.
4. ^ Goto A, Takeuchi S, Sugimura K, Maruo T (2002). "Usefulness of Gd-DTPA contrast-enhanced dynamic MRI and serum determination of LDH and its isozymes in the differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus". Int. J. Gynecol. Cancer 12 (4): 354-61. PMID 12144683.