Uterine tumors

Uterine tumors can be divided into:

Benign tumors:
1. Endometrial polyp 2. Uterine Fibroids 3. Adenomyosis

Malignant tumors:
1. Endometrial Carcinoma 2. Mixed Mesodermal tumor 3. Leiomyosarcoma

Endometrial polyp
An endometrial polyp or uterine polyp is a mass in the inner lining of the uterus. They range in size from a few millimeters to several centimeters. Endometrial polyps usually occur in women in their 40s and 50s. Endometrial polyps occur in up to 10% of women. Risk factors include: 1. Obesity 2. High blood pressure

3. History of cervical polyps. 4. Taking tamoxifen or hormone replacement therapy can also increase the risk of uterine polyps. They may be:

Sessile: They have flat bases. Pedunculated : They are attached to the uterus by an elongated pedicle. They are more common
and can be protuded through the cervix into vagina.

Etiology:
No definitive cause of endometrial polyps is known, but they appear to be affected by hormone levels and grow in response to circulating estrogen.

Symptoms:
They often cause no symptoms. When they occur,they include: 1. Irregular menstrual bleeding. 2. Bleeding between menstrual periods. 3. Excessively heavy menstrual bleeding. 4. Vaginal bleeding after menopause. 5. If the polyp protrudes through the cervix into the vagina, pain (dysmenorrhea) may result.

Investigations:
1. Vaginal ultrasound (sonohysterography) 2. Hysteroscopy and dilation and curettage.

Treatment:
Polyps can be surgically removed using curettage with or without hysteroscopy under general anesthesia.

Complications:
Endometrial polyps are usually benign although some may be precancerous or cancerous. About 0.5% of endometrial polyps contain adenocarcinoma cells. Polyps can increase the risk of miscarriage in women undergoing IVF treatment. If they develop near the fallopian tubes, they may lead to difficulty in becoming pregnant.

Uterine fibroid
A uterine fibroid (also uterine leiomyoma, fibromyoma, leiofibromyoma, fibroleiomyoma, and fibroma) (the plural of myoma is myomas or myomata) is a benign (non-cancerous) tumor that originates from the smooth muscle layer (myometrium) and the accompanying connective tissue of the uterus.
Fibroids are the most common benign tumors in females and typically found during the middle and later reproductive years. While most fibroids are asymptomatic, they can grow and cause heavy and painful menstruation, painful sexual intercourse, and urinary frequency and urgency. Some fibroids may interfere with pregnancy although this appears to be very rare

In the US, symptoms caused by uterine fibroids are a very frequent indication for hysterectomy. Fibroids are often multiple and if the uterus contains too many leiomyomata to count, it is referred to as diffuse uterine leiomyomatosis. The malignant version of a fibroid is extremely uncommon and termed a leiomyosarcoma

Symptoms:
Fibroids, particularly when small, may be entirely asymptomatic. Symptoms depend on the location of the lesion and its size. Important symptoms include abnormal gynecologic hemorrhage, heavy or painful periods, abdominal discomfort or bloating, painful defecation, back ache, urinary frequency or retention, and in some cases, infertility. 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.

Classification:

Intramural fibroids are located within the wall of the uterus and are the most common type; unless large, they may be asymptomatic. Intramural fibroids begin as small nodules in the muscular wall of the uterus. With time, intramural fibroids may expand inwards, causing distortion and elongation of the uterine cavity.

Subserosal fibroids are located underneath the mucosal (peritoneal) surface of the uterus and can become very large. They can also grow out in a papillary manner to become pedunculated fibroids. These pedunculated growths can actually detach from the uterus to become a parasitic leiomyoma. Submucosal fibroids are located in the muscle beneath the endometrium of the uterus and distort the uterine cavity; even small lesion in this location may lead to bleeding and infertility. A pedunculated lesion within the cavity is termed an intracavitary fibroid and can be passed through the cervix. Cervical fibroids are located in the wall of the cervix (neck of the uterus). Rarely fibroids are found in the supporting structures (round ligament, broad ligament, or uterosacral ligament) of the uterus that also contain smooth muscle tissue

gynecologic ultrasonography (ultrasound) MRI) hysterosalpingography or sonohysterography. From Wikipedia, the free encyclopedia

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Uterine fibroids
Classification and external resources

Uterine Fibroids

ICD-10

D25.

ICD-9

218.9

OMIM

150699

DiseasesDB

4806

eMedicine

radio/777

MeSH

D007889

A uterine fibroid (also uterine leiomyoma,[1] myoma, fibromyoma, leiofibromyoma, fibroleiomyoma, and fibroma) (the plural of myoma is myomas or myomata) is a benign (noncancerous) tumor that originates from the smooth muscle layer (myometrium) and the accompanying connective tissue of the uterus. Fibroids are the most common benign tumors in females and typically found during the middle and later reproductive years. While most fibroids are asymptomatic, they can grow and cause heavy and painful menstruation, painful sexual intercourse, and urinary frequency and urgency. Some fibroids may interfere with pregnancy although this appears to be very rare.[2] In the US, symptoms caused by uterine fibroids are a very frequent indication for hysterectomy.[3] Fibroids are often multiple and if the uterus contains too many leiomyomata to count, it is referred to as diffuse uterine leiomyomatosis. The malignant version of a fibroid is extremely uncommon and termed a leiomyosarcoma.

Contents

1 Signs and symptoms 2 Pathophysiology o 2.1 Location o 2.2 Pathogenesis 3 Diagnosis o 3.1 Coexisting disorders 4 Treatment o 4.1 Medication o 4.2 Uterine artery embolization o 4.3 Uterine artery ligation o 4.4 Radio frequency ablation o 4.5 Myomectomy o 4.6 Hysterectomy o 4.7 Endometrial ablation o 4.8 Magnetic resonance guided focused ultrasound 5 Epidemiology o 5.1 In African-Americans 6 Prognosis o 6.1 Metastasis 7 Society and culture o 7.1 United States law 8 In other animals

9 References

[edit] Signs and symptoms

Fibroids, particularly when small, may be entirely asymptomatic. Symptoms depend on the location of the lesion and its size. Important symptoms include abnormal gynecologic hemorrhage, heavy or painful periods, abdominal discomfort or bloating, painful defecation, back ache, urinary frequency or retention, and in some cases, infertility.[4] 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. The U.S. Department of Health & Human Services states that "Fibroids are almost always benign (not cancerous). Rarely (less than one in 1,000) a cancerous fibroid will occur. This is called leiomyosarcoma. Doctors think that these cancers do not arise from an already-existing fibroid. Having fibroids does not increase the risk of developing a cancerous fibroid. Having fibroids also does not increase a woman's chances of getting other forms of cancer in the uterus."[5] While fibroids are common, they are not a typical cause for infertility accounting for about 3% of reasons why a woman may not have a child.[6] Typically in such cases a fibroid is located in a submucosal position and it is thought that this location may interfere with the function of the lining and the ability of the embryo to implant.[6] Also larger fibroids may distort or block the fallopian tubes.

[edit] Pathophysiology
Leiomyomas grossly appear as round, well circumscribed (but not encapsulated), solid nodules that are white or tan, and show whorled appearance on histological section. 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.

Micrograph of a lipoleiomyoma, a type of leiomyoma. H&E stain.

Microscopically, tumor cells resemble normal cells (elongated, spindle-shaped, with a cigarshaped nucleus) and form bundles with different directions (whorled). These cells are uniform in size and shape, with scarce mitoses. There are three benign variants: bizarre (atypical); cellular; and mitotically active.

[edit] Location

An enucleated uterine leiomyoma external surface on left, cut surface on right.

large subserosal fibroid Growth and location are the main factors that determine if a fibroid leads to symptoms and problems.[3] A small lesion can be symptomatic if located within the uterine cavity while a large lesion on the outside of the uterus may go unnoticed. Different locations are classified as follows:

Intramural fibroids are located within the wall of the uterus and are the most common type; unless large, they may be asymptomatic. Intramural fibroids begin as small nodules in the muscular wall of the uterus. With time, intramural fibroids may expand inwards, causing distortion and elongation of the uterine cavity. Subserosal fibroids are located underneath the mucosal (peritoneal) surface of the uterus and can become very large. They can also grow out in a papillary manner to become pedunculated fibroids. These pedunculated growths can actually detach from the uterus to become a parasitic leiomyoma. Submucosal fibroids are located in the muscle beneath the endometrium of the uterus and distort the uterine cavity; even small lesion in this location may lead to bleeding and infertility. A pedunculated lesion within the cavity is termed an intracavitary fibroid and can be passed through the cervix.

Cervical fibroids are located in the wall of the cervix (neck of the uterus). Rarely fibroids are found in the supporting structures (round ligament, broad ligament, or uterosacral ligament) of the uterus that also contain smooth muscle tissue.

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 or towards the internal cavity. Secondary changes that may develop within fibroids are hemorrhage, necrosis, calcification, and cystic changes.

[edit] Pathogenesis
Fibroids are monoclonal tumors, approximately 40 to 50% show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the MED12 protein, have been noted in 70 percent of fibroids.[7] Exact aetiology is not clearly understood, current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause fibroid growth. Known risk factors are African-American descent, nulliparity, obesity, polycystic ovary syndrome, diabetes and hypertension.[8] Fibroid growth is strongly dependent on estrogen and progesterone. Although both estrogen and progesterone are usually regarded as growth promoting they will also cause growth restriction in some circumstances. Paradoxically fibroids will rarely grow during pregnancy despite very high steroid hormone levels and pregnancy appears to exert a certain protective effect.[2] This protective effect might be partially mediated by an interaction estrogen and the oxytocin receptor.[9] It is believed that estrogen and progesterone have both mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of growth factors, cytokines and apoptotic factors as well as other hormones. Furthermore the actions of estrogen and progesterone are modulated by the cross-talk between estrogen, progesterone and prolactin signalling which controls the expression of the respective nuclear receptors. It is believed that estrogen is growth promoting by up-regulating IGF-1, EGFR, TGF-beta1, TGF-beta3 and PDGF, promotes aberrant survival of leiomyoma cells by down-regulating p53, increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signalling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF, TGF-beta1 and TGFbeta3, and the survival through up-regulating Bcl-2 expression and down-regulating TNF-alpha. Progesterone is believed to counteract growth by downregulating IGF-1.[10][11][12] Expression of transforming growth interacting factor (TGIF) is increased in leiomyoma compared with myometrium.[13] TGIF is a potential repressor of TGF- pathways in myometrial cells.[13] Whereas in premenopausal fibroids the ER-beta, ER-alpha and progesterone receptors are found overexpressed, in the rare postmenopausal fibroids only ER-beta was found significantly overexpressed.[14] Most studies found that polymorphisms in ER and PR gene encodings are not correlated with incidence of fibroids in Caucasian populations[15][16] however a special ER-alpha

genotype was found correlated with incidence and size of fibroids. The higher prevalence of this genotype in black women may also explain the high incidence of fibroids in this group.[17] Uterine leiomyoma was more sensitive than normal myometrium to PPAR-gamma receptor activation resulting in reduced survival and apoptosis of leiomyoma cells. The mechanism is thought to involve negative cross-talk between ER and PPAR signaling pathways. Several PPAR-gamma ligands were considered as potential treatment.[18] PPAR-gamma agonists may also counteract leiomyoma growth by several other mechanisms of action such as TGF-beta3 expression inhibition.[19] Hypertension is significantly correlated with fibroids. Although a causal relationships is not at all clear the hypothesis has been formulated that atherosclerotic injury to uterine blood vessels and the resulting inflammatory state may play a role. Furthermore endocrine factors related to blood pressure such as angiotensin II are suspected to cause fibroid proliferation via angiotensin II type 1 receptor.[20][21] Aromatase and 17beta-hydroxysteroid dehydrogenase are aberrantly expressed in fibroids, indicating that fibroids can convert circulating androstenedione into estradiol.[22] Similar mechanism of action has been elucidated in endometriosis and other endometrial diseases.[23] Aromatase inhibotors are currently considered for treatment, at certain doses they would completely inhibit estrogen production in the fibroid while not largely affecting ovarian production of estrogen (and thus systemic levels of it). Aromatase overexpression is particularly pronounced in Afro-American women[24] Genetic and hereditary causes are being considered and several epidemiologic findings indicate considerable genetic influence especially for early onset cases. First degree relatives have a 2.5fold risk, and nearly 6-fold risk when considering early onset cases. Monozygotic twins have double concordance rate for hysterectomy compared to dizygotic twins.[25] Like keloids, fibroids have disregulated production of extracellular matrix. Recent studies suggest that this production may represent an abnormal response to ischemic and mechanical tissue stress.[26] Several factors indicate significant involvement of extracellular signaling pathways such as ERK1 and ERK2, which in fibroids are prominently influenced by hormones.[27] Paradoxically and unlike most other conditions involving significant fibrosis the Cyr61 gene has been found downregulated in fibroids.[28] Cyr61 is also known for its role as tumor suppressing factor and in angiogenesis. Hence fibroids are one of the very few tumors with reduced vascular density.[28]

[edit] Diagnosis
While a bimanual examination typically can identify the presence of larger fibroids, gynecologic ultrasonography (ultrasound) has evolved as the standard tool to evaluate the uterus for fibroids. Sonography will depict the fibroids as focal masses with a heterogeneous texture, which usually cause shadowing of the ultrasound beam. The location can be determined and dimensions of the

lesion measured. Also magnetic resonance imaging (MRI) can be used to define the depiction of the size and location of the fibroids within the uterus. Imaging modalities cannot clearly distinguish between the benign uterine leiomyoma and the malignant uterine leiomyosarcoma, however, the latter is quite rare. Fast growth or unexpected growth, such as enlargement of a lesion after menopause, raise the level of suspicion that the lesion might be a sarcoma. Also, with advanced malignant lesions there may be evidence of local invasion. A more recent study has suggested that diagnostic capabilities using MRI have improved the ability to detect sarcomatous lesions.[29] Biopsy is rarely performed and if performed, is rarely diagnostic. Should there be an uncertain diagnosis after ultrasounds and MRI imaging, surgery is generally indicated. Other imaging techniques that may be helpful specifically in the evaluation of lesions that affect the uterine cavity are hysterosalpingography or sonohysterography.

A very large (9cm) fibroid of the uterus which is causing pelvic congestion syndrome as seen on CT

A very large (9cm) fibroid of the uterus which is causing pelvic congestion syndrome as seen on US]]

A relatively large submucosal leiomyoma; it fills out the major part of the endometrial cavity

A small uterine fibroid seen within the wall of the myometrium on a cross sectional ultrasound view

[edit] Coexisting disorders

Fibroids that lead to heavy vaginal bleeding lead to anemia and iron deficiency. Due to pressure effects gastrointestinal problems are possible such as constipation and bloatedness. Compression of the ureter may lead to hydronephrosis. Fibroids may also present alongside endometriosis, which itself may cause infertility. Adenomyosis may be mistaken for or coexist with fibroids. In very rare cases, malignant (cancerous) growths, leiomyosarcoma, of the myometrium can develop.[30]

[edit] Treatment
Most fibroids do not require treatment unless they are causing symptoms. After menopause fibroids shrink and it is unusual for fibroids to cause problems. Symptomatic uterine fibroids can be treated by:

medication to control symptoms medication aimed at shrinking tumours ultrasound fibroid destruction various surgically aided methods to reduce blood supply of fibroids myomectomy or radio frequency ablation hysterectomy treatment for infection and anemia embolization

Eighty percent of African-American women will develop benign uterine fibroid tumors by their late 40s, according to the National Institute of Environmental Health Sciences. About 1 out of 1000 lesions[6] are or become malignant, typically as a leiomyosarcoma on histology. A sign that a lesion may be malignant is growth after menopause.[6] 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