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 benign 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.

Fibroids are named according to where they are found. There are four types: Intramural fibroids are found in the wall of the womb and are the most common type of fibroids. Subserosal fibroids are found growing outside the wall of the womb and can become very large. They can also grow on stalks (called pedunculated fibroids). Submucosal fibroids are found in the muscle beneath the inner lining of the womb wall. Cervical fibroids are found in the wall of the cervix (neck of the womb). In very rare cases, malignant (cancerous) growths on the smooth muscles inside the womb can develop, called leiomyosarcoma of the womb. [ [http://www.nhs.uk/Conditions/Fibroids/Pages/Introduction.aspx?url=Pages/What-is-it.aspx Fibroids - What is it? - Introduction ] ]

Pathology and histology

Leiomyomas grossly appear as round, well circumscribed (but not encapsulated), solid nodules that are white or tan, and 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). [ [http://www.fibroids.net/aboutfibroids.html Center For Uterine Fibroids - Information About Fibroids ] ]

Leiomyomas are estrogen sensitive and have estrogen receptors. They may enlarge rapidly during pregnancy due to increased estrogen levels. Fibroids tend to regress following menopause because of lowered levels of estrogen. Hormonal therapy is based on these facts.

More recent studies have revealed a possible role of progesterone and progestins to fibroid growth as well,cite journal |author=Nisolle M, Gillerot S, Casanas-Roux F, Squifflet J, Berliere M, Donnez J |title=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 |journal=Hum. Reprod. |volume=14 |issue=11 |pages=2844–50 |year=1999 |pmid=10548634 |doi= 10.1093/humrep/14.11.2844|url=http://humrep.oxfordjournals.org/cgi/content/full/14/11/2844 ] [cite web |url=http://ehp.niehs.nih.gov/members/2000/suppl-5/791-793rein/rein-full.html |title=Advances in Uterine Leiomyoma Research: The Progesterone Hypothesis |accessdate=2007-08-25 |format= |work=] and applicability of progestin agonists as part of treatment are currently being considered.cite journal |author=Celik H, Sapmaz E |title=Use of a single preoperative dose of misoprostol is efficacious for patients who undergo abdominal myomectomy |journal=Fertil. Steril. |volume=79 |issue=5 |pages=1207–10 |year=2003 |pmid=12738519 |doi=10.1016/S0015-0282(03)00076-1]


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, heavy or painful periods, abdominal discomfort or bloating, back ache, urinary frequency or retention, and in some cases, infertility. [ [http://womenshealth.about.com/cs/fibroidtumors/a/fibroidtumors.htm Fibroid Tumors ] ] There may also be pain during intercourse, depending on the location of the fibroid. During pregnancy they may be the cause of miscarriage, bleeding, premature labor, or interference with the position of the fetus.


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 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. This imaging modality is required when non surgical treatment such as uterine fibroid embolization is suggested. 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.cite journal |author=Goto A, Takeuchi S, Sugimura K, Maruo T |title=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 |journal=Int. J. Gynecol. Cancer |volume=12 |issue=4 |pages=354–61 |year=2002 |pmid=12144683 |doi=10.1046/j.1525-1438.2002.01086.x] For this reason, biopsy is rarely performed and if performed, is rarely diagnostic. Should there be an uncertain diagnosis after ultrasounds and MRI imaging, or should there be questions regarding whether the fibroid is interfering with fertility, a laparoscopy is one option for further information to be gathered regarding the exact size and location of the fibroid. Fibroids may also present alongside endometriosis, which itself may cause infertility.


The presence of fibroids does not mean that they need to be treated; it is expectantly depending on the symptomatology and presence of related conditions.The presence of uterine fibroids can cause problems which can be solved by:
*Surgery: Surgical removal of a uterine fibroid usually takes place via hysterectomy, in which the entire uterus is removed, or myomectomy, in which only the fibroid is removed. It is possible to remove multiple fibroids during a myomectomy. Although a myomectomy cannot prevent the recurrence of fibroids at a later date, such surgery is increasingly recommended, especially in the case of women who have not completed bearing children or who express an explicit desire to retain the uterus. There are three different types of myomectomy:
** In a "hysteroscopic" myomectomy, the fibroid is removed by the use of a resectoscope, an endoscopic instrument that can use high-frequency electrical energy to cut tissue. Hysteroscopic myomectomies can be done as an outpatient procedure, with either local or general anesthesia used. [ [http://www.myomectomy.net/hysteroscopic_myomectomy.htm Indman, Paul D. “Hysteroscopic Myomectomy for Removal of Uterine Fibroids,” personal web page, 2001] ] Hysteroscopic myomectomy is most often recommended for submucosal fibroids. A French study collected results from 235 patients suffering from submucous myomas who were treated with hysteroscopic myomectomies; in none of these cases was the fibroid greater than 5 cm. [Polena, V., et al. “Long-term results of hysteroscopic myomectomy in 235 patients.” "European Journal of Obstetrics & Gynecology and Reproductive Biology" 130 (2007): 232-237.]
** A "laparoscopic" myomectomy requires a small incision near the navel. The physician then inserts a laparoscope into the uterus and uses surgical instruments to remove the fibroids. Studies have suggested that laparoscopic myomectomy leads to lower morbidity rates and faster recovery than does laparotomic myomectomy. [ [http://www.ncbi.nlm.nih.gov/pubmed/18325839 Agdi, M. and Tulandi, T. “Endoscopic management of uterine fibroids.” "Best Practice & Research Clinical Obstetrics & Gynecology", online publication 4 Mar 2008.] ] As with hysteroscopic myomectomy, laparoscopic myomectomy is not generally used on very large fibroids. A study of laparoscopic myomectomies conducted between January 1990 and October 1998 examined 106 cases of laparoscopic myomectomy, in which the fibroids were intramural or subserous and ranged in size from 3 to 10 cm. [Soriano, D. et al. “Pregnancy outcome after laparoscopic and laparoconverted myomectomy.” "European Journal of Obstetrics & Gynecology and Reproductive Biology" 108 (2003): 194-198.]
** A "laparotomic" myomectomy (also known as an "open" or "abdominal" myomectomy) is the most invasive surgical procedure to remove fibroids. The physician makes an incision in the abdominal wall and removes the fibroid from the uterus. A particularly extensive laparotomic procedure may necessitate that any future births be conducted by Caesarean section. [ [http://www.asrm.org/Patients/patientbooklets/uterine_fibroids.pdf American Society of Reproductive Medicine Patient Booklet: "Uterine Fibroids", 2003] ] Recovery time from a laparatomic procedure is generally expected to be four to six weeks.
*Uterine artery embolization (UAE): Using interventional radiology techniques, the Interventional Radiologist occludes both uterine arteries, thus reducing blood supply to the fibroid [ [http://femisa.org.uk/what's_involved.htm The Embolisation Process: What's Involved ] ] . A small catheter (1 mm in diameter) is inserted into the femoral artery at the level of the groin under local anesthesia. Under imaging guidance, the interventionnal radiologist will enter selectively into both uterine arteries and inject small (500 µm) particles that will block the blood supply to the fibroids. This results in shrinking of the fibroids and of the uterus, thus alleviating the symptoms in most cases. Uterine Artery Embolization is now recognized as a viable alternative to hysterectomy and most women suffering from fibroid related symptoms can be treated with this technique.

*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 2004. [cite press release |title=FDA Approves New Device to Treat Uterine Fibroids |publisher=FDA |date=2004-10-22 |url=http://www.fda.gov/bbs/topics/answers/2004/ans01319.html |accessdate=2008-05-26]


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.

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