An enucleated<unk>  leiomyoma – external surface on left, cut surface on right.<unk> s are a type of<unk>  leiomyoma.<unk> s 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 cigar-shaped 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. The appearance of prominent nucleoli with perinucleolar halos should alert the pathologist to investigate the possibility of the extremely rare hereditary leiomyomatosis and renal cell cancer (Reed) syndrome. Location and classification Schematic drawing of various types of<unk> s: a=subserosal<unk> s, b=intramural<unk> s, c=submucosal<unk> , d=pedunculated submucosal<unk> , e=cervical<unk> , f=fibroid of the broad ligament Growth and location are the main factors that determine if a<unk>  leads to symptoms and problems. A small lesion can be symptomatic if located within the<unk>  cavity while a large lesion on the outside of the uterus may go unnoticed. Different locations are classified as follows: * Intramural<unk> s are located within the muscular wall of the uterus. Unless they are large, they may be asymptomatic. Intramural<unk> s begin as small nodules in the muscular wall of the uterus. With time, intramural<unk> s may expand inwards, causing distortion and elongation of the<unk>  cavity. * Subserosal<unk> s are located on the surface of the uterus. They can also grow outward from the surface and remain attached by a small piece of tissue and then are called pedunculated<unk> s. * Submucosal<unk> s are most common type, located in the muscle beneath the endometrium of the uterus and distort the<unk>  cavity; even small lesions in this location may lead to bleeding and infertility. A pedunculated lesion within the cavity is termed an intracavitary<unk>  and can be passed through the cervix. * Cervical<unk> s are located in the wall of the cervix (neck of the uterus). Rarely,<unk> s are found in the supporting structures (round ligament, broad ligament, or uterosacral ligament) of the uterus that also contain smooth muscle tissue.<unk> s may be single or multiple. Most<unk> s start in the muscular wall 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<unk> s are hemorrhage, necrosis, calcification, and cystic changes. They tend to calcify after menopause. If the uterus contains too many to count, it is referred to as diffuse<unk>  leiomyomatosis. Extrauterine<unk> s of<unk>  origin, metastatic<unk> s<unk> s of<unk>  origin located in other parts of the body, sometimes also called parasitic myomas have been historically extremely rare, but are now diagnosed with increasing frequency. They may be related or identical to metastasizing leiomyoma. They are in most cases still hormone dependent but may cause life-threatening complications when they appear in distant organs. Some sources suggest that a substantial share of the cases may be late complications of surgeries such as myomectomy or hysterectomy. Particularly laparoscopic myomectomy using a morcellator has been associated with an increased risk of this complication. There are a number of rare conditions in which<unk> s metastasize. They still grow in a benign fashion, but can be dangerous depending on their location. *In leiomyoma with vascular invasion, an ordinary-appearing<unk>  invades into a vessel but there is no risk of recurrence. *In intravenous leiomyomatosis, leiomyomata grow in veins with<unk> s as their source. Involvement of the heart can be fatal. *In benign metastasizing leiomyoma, leiomyomata grow in more distant sites such as the lungs and lymph nodes. The source is not entirely clear. Pulmonary involvement can be fatal. *In disseminated intraperitoneal leiomyomatosis, leiomyomata grow diffusely on the peritoneal and omental surfaces, with<unk> s as their source. This can simulate a malignant tumor but behaves benignly. Pathogenesis Multiple<unk>  leiomyoma Large subserosal<unk>  Multiple<unk>  leiomyoma with calcification<unk> s are monoclonal tumors and approximately 40 to 50% show karyotypically detectable chromosomal abnormalities. When multiple<unk> s are present they frequently have unrelated genetic defects. Specific mutations of the MED12 protein have been noted in 70 percent of<unk> s. The exact cause of<unk> s is not clearly understood, but the current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause<unk>  growth. Known risk factors are African descent, obesity, polycystic ovary syndrome, diabetes, hypertension, and never having given birth. It is believed that estrogen and progesterone have a 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 signaling which controls the expression of the respective nuclear receptors. It is believed that estrogen promotes growth by up-regulating IGF-1, EGFR, TGF-beta1, TGF-beta3 and PDGF, and promotes aberrant survival of leiomyoma cells by down-regulating p53, increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signaling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF, TGF-beta1 and TGF-beta3, and promotes survival through up-regulating Bcl-2 expression and down-regulating TNF-alpha. Progesterone is believed to counteract growth by downregulating IGF-1. Expression of transforming growth interacting factor (TGIF) is increased in leiomyoma compared with myometrium. TGIF is a potential repressor of TGF-β pathways in myometrial cells. Aromatase and 17beta-hydroxysteroid dehydrogenase are aberrantly expressed in<unk> s, indicating that<unk> s can convert circulating androstenedione into estradiol. Similar mechanism of action has been elucidated in endometriosis and other endometrial diseases. Aromatase inhibitors are currently considered for treatment, at certain doses they would completely inhibit estrogen production in the<unk>  while not largely affecting ovarian production of estrogen (and thus systemic levels of it). Aromatase overexpression is particularly pronounced in African-American women. 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 2.5-fold risk, and nearly 6-fold risk when considering early onset cases. Monozygotic twins have double concordance rate for hysterectomy compared to dizygotic twins. Expansion of<unk> s occurs by a slow rate of cell proliferation combined with the production of copious amounts of extracellular matrix. A small population of the cells in a<unk>  have properties of stem cells or progenitor cells, and contribute significantly to ovarian steroid-dependent growth of<unk> s. These stem-progenitor cells are deficient in estrogen receptor α and progesterone receptor and instead rely on substantially higher levels of these receptors in surrounding differentiated cells to mediate estrogen and progesterone actions via paracrine signaling.
Uterine fibroid
Uterine inversion
Leiomyoma
Cervical pregnancy
Endometrioid tumor
Ovarian pregnancy
Pelvic lipomatosis
Endometriosis