Pathology

Fibroids of the uterus, also known as uterine leiomyomas or myomas, are benign smooth-muscle cells along with fibrous tissue from the main body of the uterus. The muscle cells grow in whirls that form ball-shaped growths varying from 1mm to over 20cm in diameter. If the growth starts near the outside of the uterus, the growth becomes a subserosal fibroid. If it starts near the middle of the uterus it is an intramural fibroid and if it starts near the inside endometrial lining, it becomes a submucosal fibroid.

Fibroids are composed of uterine smooth-muscle cells that are “monoclonal”, i.e., all of the muscle cells in a leiomyoma are descendents of one cell that has reproduced itself extensively. It is not known whether the initial or ongoing stimulus is genetic, viral, inflammatory repair of normal cell loss some other cause.

Fibroids may be single or multiple. Most fibroids start in an intramural location. 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: haemorrhage, necrosis, calcification, and cystic changes. Less frequently, leiomyomas may occur at the lower uterine segment, cervix, or uterine ligaments.

Leiomyomas are oestrogen sensitive and have oestrogen receptors. They may enlarge rapidly during pregnancy due to increased oestrogen levels. As oestrogen levels decline with menopause, fibroids tend to regress. Hormonal therapy is based on these facts. Contraceptive pills probably play a role in stimulating fibroid growth and the fibroids may regress in size when the pills are stopped . As to whether oral contraceptives cause an increased fibroid incidence, the studies are somewhat conflicting from no increased incidence to a slightly increased incidence. It was previously thought that just oestrogen was necessary for growth but it now appears the progesterone is critical to fibroid growth.

Taking postmenopausal oestrogen and progestin replacement therapy can cause fibroids to grow. It appears that the progesterone/progestin component is needed because that is the hormone that increases cell reproduction (mitotic activity) in the fibroid itself.

Incidence

Fibroids are very common and it is estimated that around half of women over the age of 40 and 70-80% of women over the age of 50 are affected. Fibroids are almost unknown before an adolescent starts having menstrual periods. They grow slowly unless they are under the stimulation of extra oestrogen and progesterone such as oral contraceptives. After menopause, the fibroids and entire uterus get smaller unless hormone replacement therapy is given. Fibroids shrink as more time after menopause passes. They may become calcified and it is not unusual to have an incidental X-ray or ultrasound finding in a patient in their 70s or 80s show round calcified areas in the region of the uterus.

Symptoms

The symptoms depend on the size, location, number, and 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 increased or prolonged menstrual bleeding, painful menstruation, urinary frequency or retention, and in some cases, infertility. During pregnancy they may be the cause of miscarriage, bleeding, premature labour, or interference with the position of the foetus.

Most of these tumours are asymptomatic. Leiomyomas can produce acute pelvic pain if they outgrow their blood supply. This is called auto- or spontaneous infarction of a leiomyoma and the pain lasts for several days to a week or more.

Pelvic pressure and fullness present when the size of the uterus with the fibroids(s) grows as big as a 3-4 month pregnancy. If the fibroids are on the anterior uterine surface they can cause bladder pressure and urgency and if on the posterior surface, they may produce rectal urgency.

Abnormal menstrual bleeding is a problem if there is one or more submucosal fibroid or if an intramural fibroid gets so big that it impinges upon the endometrial cavity and compromises the blood supply to the base of the uterine lining.

Fibroids, depending on their location, can interfere with fertility.

Diagnosis

Diagnosis is usually accomplished by ultrasound. Fibroids usually present as a central lower abdominal mass rather than totally involving the adnexa. Ultrasound imaging often can differentiate uterine leiomyomas from ovarian tumours, but not always. 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, magnetic resonance imaging (MRI) can also be used to clearly delineate 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, the rarity of the latter and the prevalence of the former make it, for practical purposes, a non-issue unless evidence of local invasion is present.

Microscopic analysis is the gold standard to differentiate a benign leiomyoma from a malignant leiomyosarcoma. The pathologist looks for the active number of cell mitoses per high power microscopic field. The definition of less than 5 mitoses per 10 high powered fields or less than 4 mitoses is a commonly used criteria for declaring a fibroid as benign but the pathologist also looks for cellular atypia and coagulative tumor cell necrosis and sometimes DNA ploidy in making this judgement.

One of the most common conditions confused with fibroids is adenomyosis. In adenomyosis the lining of the uterus infiltrates the wall of the uterus, causing the wall to thicken and the uterus to enlarge. On ultrasound examination this will often appear as diffuse thickening of the wall, while fibroids are seen as round areas with a discrete border. Adenomyosis is usually a diffuse process, and can rarely be removed without taking out the uterus. Since fibroids can be removed, it is important to differentiate between the two conditions before planning treatment. It is also common to have some adenomyosis in addition to fibroids.

Treatment options

In most cases no treatment at all is necessary. The fibroids are measured and observed over time, with the expectation that at menopause, they will regress. So, prior to menopause the goal is to keep the fibroids from growing too large or too fast. If a woman can get to menopause without having symptoms from the fibroids, then it is likely that she will never have problems from the growths that require treatment.

If there are symptoms of abnormal uterine bleeding, the therapeutic goal is to control the bleeding. If the symptoms are pelvic pressure due to the size of the fibroids, surgical removal, myomectomy, hysterectomy, or shrinkage of the fibroids is the goal.

Therapy is very dependent upon what symptoms a woman has, the impact of these symptoms on her quality of life, and whether she is trying to conceive now or in the not too distant future. For those with significant symptoms, very large fibroids, or rapidly growing fibroids, a number of treatments can be considered.

Hysterectomy

This is the only permanent cure for fibroids. It provides definitive treatment, but requires major abdominal, vaginal or laparoscopic surgery.

Myomectomy

Removal of just the fibroid, with conservation of the rest of the uterus. This can be accomplished through laparoscopy, or by an open procedure. For women who wish to preserve their childbearing capacity this option may be the best.

Hormonal therapy

Oral contraceptive pills, either combination pills or progestin-only can be used to manage symptoms. If unsuccessful, further medical therapy involves the use of medication to reduce oestrogens in an attempt to create a medical menopause-like situation. Gonadotropin-releasing hormone analogs are used for this. GNRH analogues, however, are short term treatments only. While these will not shrink fibroids, they may be effective enough in controlling the symptoms (particularly bleeding) that the patient can make it through to menopause without requiring further treatment.

Embolisation

Under fluoroscopic guidance, a catheter is threaded through the uterine arteries and a bolus of tiny plastic pellets is injected. These pellets lodge in the small arterioles leading to the fibroids, reducing their blood flow and causing necrosis.

High intensity focused ultrasound (HIFU)

Also called magnetic resonance guided focused ultrasound, this is a non-invasive intervention that uses high intensity focused ultrasound waves to ablate tissue in combination with MRI, which guides and monitors the treatment.


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